Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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{| class="wikitable" style="text-align:center; width:100%;"
 
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! colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26" |'''Page editor'''
 
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! colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26" |'''Section editor'''
 
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|-
 
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| style="background-color:#F0F0F0; width:15%" |[[File:mary_kwok.jpg|frameless|upright=0.3|center]]
 
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| style="width:35%" |<big>Mary L. Kwok, MD, FACP<br>Seattle Cancer Care Alliance<br>Seattle, WA</big>
 
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| style="background-color:#F0F0F0; width:15%" |[[File:Headshot Cowan.jpg|frameless|upright=0.3|center]]
 
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| style="width:35%" |<big>[[User:Andrewc072|Andrew J. Cowan, MD]]<br>University of Washington<br>Seattle, WA</big><br>[[File:Social-twitter-icon.png|frameless|upright=0.1]] [https://twitter.com/andrewcowanmd andrewcowanmd]<br>[https://www.linkedin.com/in/andrew-cowan-63b3a130/ LinkedIn]
 
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|-
 
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|}
 
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''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Multiple_myeloma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''.
 
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<br><big>'''Note: due to its size/complexity, multiple myeloma has been split into sub-pages:'''
 
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*[[Multiple_myeloma,_induction|Induction (transplant eligible and ineligible)]]
 
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*[[Multiple_myeloma,_consolidation_and_maintenance|First-line consolidation and maintenance]]
 
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*Relapsed/refractory, including subsequent consolidation and maintenance [''this page'']
 
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*[[Smoldering multiple myeloma]]
 
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</big>
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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|}
 
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{{TOC limit|limit=3}}
 
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{{#lst:Multiple myeloma|guidelines}}
 
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<section begin=rrmm />
 
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=Relapsed or refractory, single agents=
 
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==Belantamab mafodotin monotherapy {{#subobject:e26hvb|Regimen=1}}==
 
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<div class="toccolours" style="background-color:#eeeeee">
 
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===Regimen {{#subobject:59c6346|Variant=1}}===
 
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{| class="wikitable" style="color:white; background-color:#404040"
 
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|<small>'''FDA-recommended dose'''</small>
 
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|-
 
−
|}
 
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{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
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!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(19)30788-0 Lonial et al. 2019 (DREAMM-2)]
 
−
|2018-2019
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|-
 
−
|}
 
−
''Note: while this was a randomized trial, it was not comparative between the arms.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Belantamab mafodotin (Blenrep)]] 2.5 mg/kg IV over 30 minutes once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''DREAMM-2:''' Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Lendvai N, Sborov D, Suvannasankha A, Weisel K, Karlin L, Libby E, Arnulf B, Facon T, Hulin C, Kortüm KM, Rodríguez-Otero P, Usmani SZ, Hari P, Baz R, Quach H, Moreau P, Voorhees PM, Gupta I, Hoos A, Zhi E, Baron J, Piontek T, Lewis E, Jewell RC, Dettman EJ, Popat R, Esposti SD, Opalinska J, Richardson P, Cohen AD. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020 Feb;21(2):207-221. Epub 2019 Dec 16. [https://doi.org/10.1016/s1470-2045(19)30788-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31859245 PubMed] NCT03525678
 
−
##'''Update:''' Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Sborov D, Suvannasankha A, Weisel K, Voorhees PM, Womersley L, Baron J, Piontek T, Lewis E, Opalinska J, Gupta I, Cohen AD. Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Cancer. 2021 Nov 15;127(22):4198-4212. Epub 2021 Jul 27. [https://doi.org/10.1002/cncr.33809 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8597112/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34314018/ PubMed]
 
−
==Ciltacabtagene autoleucel monotherapy {{#subobject:8ughace|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:beyyd3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(21)00933-8 Berdeja et al. 2021 (CARTITUDE-1)]
 
−
|2018-2019
 
−
| style="background-color:#91cf61" |Phase 1b/2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Ciltacabtagene autoleucel (Carvykti)]] 0.75 × 10<sup>6</sup> CAR-positive viable T cells/kg IV once on day 0
 
−
'''One course'''
 
−
</div></div>
 
−
===References===
 
−
#'''CARTITUDE-1:''' Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, Stewart AK, Hari P, Htut M, Lesokhin A, Deol A, Munshi NC, O'Donnell E, Avigan D, Singh I, Zudaire E, Yeh TM, Allred AJ, Olyslager Y, Banerjee A, Jackson CC, Goldberg JD, Schecter JM, Deraedt W, Zhuang SH, Infante J, Geng D, Wu X, Carrasco-Alfonso MJ, Akram M, Hossain F, Rizvi S, Fan F, Lin Y, Martin T, Jagannath S. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021 Jul 24;398(10297):314-324. Epub 2021 Jun 24. Erratum in: Lancet. 2021 Oct 2;398(10307):1216. [https://doi.org/10.1016/s0140-6736(21)00933-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34175021/ PubMed] NCT03548207
 
−
==Carfilzomib monotherapy {{#subobject:36c1ce|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 15/20/27 dosing, for renal impairment {{#subobject:bdffd3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740399/ Badros et al. 2013 (PX-171-005)]
 
−
|2008-2010
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#8c6bb1" |ORR: 25.5%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 15 mg/m<sup>2</sup> IV over 2 to 10 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
**Cycle 2: 20 mg/m<sup>2</sup> IV over 2 to 10 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
**Cycle 3 onwards: 27 mg/m<sup>2</sup> IV over 2 to 10 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
====Supportive therapy====
 
−
*[[Dexamethasone (Decadron)]] 4 mg (route not specified) before all doses in cycle 1. Continue dexamethasone premedication if patients experience "treatment-related fever, chills, and/or dyspnea."
 
−
*"All patients were "required to be well hydrated."
 
−
'''28-day cycle for 12 cycles or longer if deriving clinical benefit'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with less than PR after 2 cycles or less than CR after 4 cycles were allowed to escalate to [[#Carfilzomib_.26_Dexamethasone_.28Kd.29|Kd]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 20/20 dosing {{#subobject:0b775a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818209/ Vij et al. 2012b (PX-171-004 bortezomib-exposed)]
 
−
|2007-2008
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#88419d; color:white |ORR: 17%
 
−
|-
 
−
|[https://doi.org/10.1016/j.clml.2012.08.003 Jagannath et al. 2012 (PX-171-003-A0)]
 
−
|NR in abstract
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#88419d; color:white |ORR: 17%
 
−
|-
 
−
|}
 
−
''Note: Patients enrolled in PX-171-004 could continue therapy beyond 12 cycles on PX-171-010; results of this extension study have not been published, to our knowledge.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9, 15, 16
 
−
'''28-day cycle for up to 12 cycles (see note)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 20/27 dosing, variant #1 {{#subobject:270a70|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220126/ Hájek et al. 2016 (FOCUS)]
 
−
|2010-2012
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
−
|1. [[#Cyclophosphamide_.26_Dexamethasone|Cyclophosphamide & Dexamethasone]]<br> 2. [[#Cyclophosphamide_.26_Prednisone|CP]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS <br>(HR 0.98, 95% CI 0.76-1.25)
 
−
|-
 
−
|}
 
−
''Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have ORRs greater than 20%.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*At least 3 lines of therapy including bortezomib, lenalidomide or thalidomide, an alkylating agent, and corticosteroids
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1 & 2, then 27 mg/m<sup>2</sup> IV over 10 minutes once per day on days 8, 9, 15, 16
 
−
**Cycles 2 to 9: 27 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
**Cycle 10 onwards: 27 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1, 2, 15, 16
 
−
====Supportive therapy====
 
−
*IV and PO hydration required for cycle 1
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycle 1: 4 mg IV or PO once per day on days 1, 2, 8, 9, 15, 16, given prior to [[Carfilzomib (Kyprolis)]]
 
−
*[[Ciprofloxacin (Cipro)]] as follows:
 
−
**Cycle 1: 500 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 20/27 dosing, variant #2 {{#subobject:51e1ba|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785611/ Watanabe et al. 2016]
 
−
|2011-2014
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
| style="background-color:#88419d; color:white |ORR: 22.5%
 
−
|-
 
−
|}
 
−
''Note: This is the maximum predetermined dose, there was no MTD; ORR is reported for the phase 2 portion.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 27 mg/m<sup>2</sup> IV once per day on days 8, 9, 15, 16
 
−
**Cycle 2 onwards: 27 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9, 15, 16
 
−
====Supportive therapy====
 
−
*IV and PO hydration required for cycle 1, then as needed
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycle 1 (required): 4 mg IV or PO once per day on days 1, 2, 8, 9, 15, 16, prior to [[Carfilzomib (Kyprolis)]]
 
−
**Cycle 2 onwards (prn): 4 mg IV or PO once per day on days 1, 2, 8, 9, 15, 16, prior to [[Carfilzomib (Kyprolis)]]
 
−
*Prophylactic antibiotics (not specified) in cycle 1
 
−
*[[Acyclovir (Zovirax)]] for patients with history of herpes infection, in cycle 1
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 20/27 dosing, with BSA cap {{#subobject:166b4f|Variant=1}}===
 
−
{| class="wikitable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123327/ Vij et al. 2012a (PX-171-004 bortezomib-naive)]
 
−
|2007-2010
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
| style="background-color:#9ebcda" |ORR: 42-52%
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123387/ Siegel et al. 2012 (PX-171-003-A1)]
 
−
|2008-2009
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
| style="background-color:#88419d; color:white |ORR: 24%
 
−
|-
 
−
|}
 
−
''Note: Neither Vij et al. 2012a nor Siegel et al. 2012 specify that carfilzomib is capped at a body surface area of 2.2 m<sup>2</sup>, but the package insert specifies that: "The dose is calculated using the patient’s actual body surface area at baseline. Patients with a body surface area greater than 2.2 m<sup>2</sup> should receive a dose based upon a body surface area of 2.2 m<sup>2</sup>. Dose adjustments do not need to be made for weight changes of less than or equal to 20%."''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> (body surface area capped at 2.2 m<sup>2</sup>) IV over 2 to 10 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
**Cycle 2 onwards: 27 mg/m<sup>2</sup> (body surface area capped at 2.2 m<sup>2</sup>) IV over 2 to 10 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
====Supportive therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycle 1: 4 mg IV or PO once per day on days 1, 2, 8, 9, 15, 16, prior to [[Carfilzomib (Kyprolis)]]
 
−
**Cycle 2: 4 mg IV or PO once on day 1, prior to [[Carfilzomib (Kyprolis)]] (Vij et al. 2012a only)
 
−
***Restart dexamethasone premedication if patients experience infusion reactions: "fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina."
 
−
*"All patients were to receive oral and intravenous fluids before dosing to assure adequate hydration."
 
−
'''28-day cycle for up to 12 cycles'''
 
−
====Dose modifications====
 
−
*"Carfilzomib was withheld for grade 3 or 4 hematologic or nonhematologic toxicities and resumed at reduced doses of 15 mg/m<sup>2</sup> in cycle 1 or 20 mg/m<sup>2</sup> in cycle 2 and above on resolution."
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, 20/56 dosing {{#subobject:2563a9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2013.52.3522 Papadopoulos et al. 2014 (PX-171-007)]
 
−
|2009-2013
 
−
|style="background-color:#91cf61"|Phase 1 (RT)
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624439/ Lendvai et al. 2014 (MSK 10-228)]
 
−
|2011-2013
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#9ebcda" |ORR: 55%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 2, then 56 mg/m<sup>2</sup> IV over 30 minutes once per day on days 8, 9, 15, 16
 
−
**Cycle 2 onwards: 56 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
====Supportive therapy====
 
−
*Normal saline pre- and post-hydration, tapered over subsequent cycles (see text for details)
 
−
*[[Dexamethasone (Decadron)]] 8 mg (route not specified) mandated with each cycle 1 dose, then optional
 
−
*[[Palonosetron (Aloxi)]] 250 mcg (route not specified) mandated with each cycle 1 dose, then optional
 
−
*[[Acyclovir (Zovirax)]] 400 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''PX-171-004 bortezomib-naive:''' Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK, Kukreti V, Jagannath S, McDonagh KT, Alsina M, Bahlis NJ, Reu FJ, Gabrail NY, Belch A, Matous JV, Lee P, Rosen P, Sebag M, Vesole DH, Kunkel LA, Wear SM, Wong AF, Orlowski RZ, Siegel DS. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012 Jun 14;119(24):5661-70. Epub 2012 May 3. [http://www.bloodjournal.org/content/119/24/5661.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123327/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22555973 PubMed] NCT00530816
 
−
# '''PX-171-004 bortezomib-exposed:''' Vij R, Siegel DS, Jagannath S, Jakubowiak AJ, Stewart AK, McDonagh K, Bahlis N, Belch A, Kunkel LA, Wear S, Wong AF, Wang M. An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib. Br J Haematol. 2012 Sep;158(6):739-48. Epub 2012 Jul 30. [https://doi.org/10.1111/j.1365-2141.2012.09232.x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818209/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22845873 PubMed] NCT00530816
 
−
# '''PX-171-003-A0:''' Jagannath S, Vij R, Stewart AK, Trudel S, Jakubowiak AJ, Reiman T, Somlo G, Bahlis N, Lonial S, Kunkel LA, Wong A, Orlowski RZ, Siegel DS. An open-label single-arm pilot phase II study (PX-171-003-A0) of low-dose, single-agent carfilzomib in patients with relapsed and refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):310-8. [https://doi.org/10.1016/j.clml.2012.08.003 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23040437 PubMed]
 
−
# '''PX-171-003-A1:''' Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, Trudel S, Kukreti V, Bahlis N, Alsina M, Chanan-Khan A, Buadi F, Reu FJ, Somlo G, Zonder J, Song K, Stewart AK, Stadtmauer E, Kunkel L, Wear S, Wong AF, Orlowski RZ, Jagannath S. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012 Oct 4;120(14):2817-25. Epub 2012 Jul 25. [http://www.bloodjournal.org/content/120/14/2817.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123387/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22833546 PubMed] '''Pivotal trial for accelerated FDA approval''' NCT00511238
 
−
## '''Subgroup analysis:''' Jakubowiak AJ, Siegel DS, Martin T, Wang M, Vij R, Lonial S, Trudel S, Kukreti V, Bahlis N, Alsina M, Chanan-Khan A, Buadi F, Reu FJ, Somlo G, Zonder J, Song K, Stewart AK, Stadtmauer E, Harrison BL, Wong AF, Orlowski RZ, Jagannath S. Treatment outcomes in patients with relapsed and refractory multiple myeloma and high-risk cytogenetics receiving single-agent carfilzomib in the PX-171-003-A1 study. Leukemia. 2013 Dec;27(12):2351-6. Epub 2013 May 14. [https://doi.org/10.1038/leu.2013.152 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865533/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23670297 PubMed]
 
−
# '''PX-171-005:''' Badros AZ, Vij R, Martin T, Zonder JA, Kunkel L, Wang Z, Lee S, Wong AF, Niesvizky R. Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety. Leukemia. 2013 Aug;27(8):1707-14. Epub 2013 Jan 31. [https://doi.org/10.1038/leu.2013.29 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740399/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23364621 PubMed] NCT00721734
 
−
# '''MSK 10-228:''' Lendvai N, Hilden P, Devlin S, Landau H, Hassoun H, Lesokhin AM, Tsakos I, Redling K, Koehne G, Chung DJ, Schaffer WL, Giralt SA. A phase 2 single-center study of carfilzomib 56 mg/m<sup>2</sup> with or without low-dose dexamethasone in relapsed multiple myeloma. Blood. 2014 Aug 7;124(6):899-906. Epub 2014 Jun 24. [http://www.bloodjournal.org/content/124/6/899 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624439/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24963043 PubMed] NCT01351623
 
−
# '''PX-171-007:''' Papadopoulos KP, Siegel DS, Vesole DH, Lee P, Rosen ST, Zojwalla N, Holahan JR, Lee S, Wang Z, Badros A. Phase I study of 30-minute infusion of carfilzomib as single agent or in combination with low-dose dexamethasone in patients with relapsed and/or refractory multiple myeloma. J Clin Oncol. 2015 Mar 1;33(7):732-9. Epub 2014 Sep 15. [https://doi.org/10.1200/JCO.2013.52.3522 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25225420 PubMed] NCT00531284
 
−
# Watanabe T, Tobinai K, Matsumoto M, Suzuki K, Sunami K, Ishida T, Ando K, Chou T, Ozaki S, Taniwaki M, Uike N, Shibayama H, Hatake K, Izutsu K, Ishikawa T, Shumiya Y, Kashihara T, Iida S. A phase 1/2 study of carfilzomib in Japanese patients with relapsed and/or refractory multiple myeloma. Br J Haematol. 2016 Mar;172(5):745-56. Epub 2016 Jan 5. [https://doi.org/10.1111/bjh.13900 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785611/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26732066 PubMed]
 
−
# '''FOCUS:''' Hájek R, Masszi T, Petrucci MT, Palumbo A, Rosiñol L, Nagler A, Yong KL, Oriol A, Minarik J, Pour L, Dimopoulos MA, Maisnar V, Rossi D, Kasparu H, Van Droogenbroeck J, Yehuda DB, Hardan I, Jenner M, Calbecka M, Dávid M, de la Rubia J, Drach J, Gasztonyi Z, Górnik S, Leleu X, Munder M, Offidani M, Zojer N, Rajangam K, Chang YL, San-Miguel JF, Ludwig H. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Leukemia. 2017 Jan;31(1):107-114. Epub 2016 Jun 24. [https://doi.org/10.1038/leu.2016.176 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220126/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27416912 PubMed] NCT01302392
 
−
==Daratumumab monotherapy {{#subobject:d45aea|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:fc9461|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa1506348 Lokhorst et al. 2015 (GEN501 part 2)]
 
−
|2008-NR
 
−
|style="background-color:#91cf61"|Phase 1/2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(15)01120-4 Lonial et al. 2016 (SIRIUS)]
 
−
|2013-NR
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/s2352-3026(20)30070-3 Mateos et al. 2020 (COLUMBA)]
 
−
|2017-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Daratumumab_and_hyaluronidase_monotherapy|Daratumumab and hyaluronidase]]
 
−
| style="background-color:#eeee01" |Non-inferior ORR
 
−
|-
 
−
|}
 
−
''Note: although SIRIUS was a randomized phase 2 trial, the randomization was to choose the dose for further assessment in an expansion cohort; the dose chosen (16 mg/kg from the start) is the one reported here:''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*GEN501 part 2: 2 or more prior therapies, including immunomodulatory agents, proteasome inhibitors, chemotherapy, and autologous stem-cell transplantation
 
−
*SIRIUS & COLUMBA: at least 3 lines of therapy including proteasome inhibitors and immunomodulatory drugs or refractory to both proteasome inhibitors and immunomodulatory drugs
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab (Darzalex)]] as follows:
 
−
**Cycles 1 & 2: 16 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 16 mg/kg IV once per day on days 1 & 15
 
−
**Cycle 7 onwards: 16 mg/kg IV once on day 1
 
−
**Per the package insert, daratumumab infusion should complete within 15 hours. In Lokhorst et al. 2015, daratumumab was given over 8 hours.
 
−
====Supportive therapy====
 
−
''This is a combination of what is listed in the daratumumab package insert and Lokhorst et al. 2015. There were protocol amendments in Lokhorst et al. 2015; listed medications are what was eventually used.''
 
−
*Prior to all daratumumab infusions:
 
−
**[[Methylprednisolone (Solumedrol)]] 100 mg IV once per infusion, prior to [[Daratumumab (Darzalex)]]
 
−
***Per the package insert, after the second dose of daratumumab, dose may be reduced to 60 mg IV. Per Lokhorst et al. 2015, after the fourth dose of daratumumab, dose "could be reduced to 50 mg."
 
−
**[[Acetaminophen (Tylenol)]] (paracetamol) 1000 mg (package insert: 650 to 1000 mg) PO once per infusion, 1 to 2 hours prior to [[Daratumumab (Darzalex)]]
 
−
**One of the following antihistamines:
 
−
***[[Clemastine (Tavist)]] 1 mg IV once per infusion, 1 to 2 hours prior to [[Daratumumab (Darzalex)]]
 
−
***[[Cetirizine (Zyrtec)]] 10 mg PO once per infusion, 1 to 2 hours prior to [[Daratumumab (Darzalex)]]
 
−
***[[Diphenhydramine (Benadryl)]] (or equivalent) 25 to 50 mg PO or IV once per infusion, 1 to 2 hours prior to [[Daratumumab (Darzalex)]]
 
−
*Post-treatment medications:
 
−
**[[Methylprednisolone (Solumedrol)]] (or equivalent) 20 to 25 mg (package insert: 20 mg) PO once per day for two days after [[Daratumumab (Darzalex)]]
 
−
**Package insert: "For patients with a history of obstructive pulmonary disorder, consider prescribing post-infusion medications such as short and long-acting bronchodilators, and inhaled corticosteroids."
 
−
*Package insert: "Initiate antiviral prophylaxis to prevent herpes zoster reactivation within 1 week of starting DARZALEX and continue for 3 months following treatment"
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Plesner, Torben, Lokhorst, Henk, Gimsing, Peter, Nahi, Hareth, Lisby, Steen, Richardson, Paul G. Daratumumab, a CD38 Monoclonal Antibody in Patients with Multiple Myeloma - Data From a Dose-Escalation Phase I/II Study. ASH Annual Meeting Abstracts 2012 120: 73 [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/73 link to abstract] -->
 
−
# '''GEN501 part 2:''' Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, Minnema MC, Lassen U, Krejcik J, Palumbo A, van de Donk NW, Ahmadi T, Khan I, Uhlar CM, Wang J, Sasser AK, Losic N, Lisby S, Basse L, Brun N, Richardson PG. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015 Sep 24;373(13):1207-19. [https://doi.org/10.1056/nejmoa1506348 link to original article] '''contains dosing details in manuscript''' [https://doi.org/10.1056/NEJMoa1506348/suppl_file/nejmoa1506348_appendix.pdf link to supplementary appendix] [https://doi.org/10.1056/NEJMoa1506348/suppl_file/nejmoa1506348_protocol.pdf link to study protocol] [https://pubmed.ncbi.nlm.nih.gov/26308596 PubMed] NCT00574288
 
−
## '''Pooled update:''' Usmani SZ, Weiss BM, Plesner T, Bahlis NJ, Belch A, Lonial S, Lokhorst HM, Voorhees PM, Richardson PG, Chari A, Sasser AK, Axel A, Feng H, Uhlar CM, Wang J, Khan I, Ahmadi T, Nahi H. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood. 2016 Jul 7;128(1):37-44. Epub 2016 May 23. [http://www.bloodjournal.org/content/128/1/37.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937359/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27216216 PubMed]
 
−
## '''Pooled update:''' Usmani SZ, Nahi H, Plesner T, Weiss BM, Bahlis NJ, Belch A, Voorhees PM, Laubach JP, van de Donk NWCJ, Ahmadi T, Uhlar CM, Wang J, Feng H, Qi M, Richardson PG, Lonial S. Daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma: final results from the phase 2 GEN501 and SIRIUS trials. Lancet Haematol. 2020 Jun;7(6):e447-e455. [https://doi.org/10.1016/s2352-3026(20)30081-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32470437/ PubMed]
 
−
<!-- # '''Abstract:''' Sagar Lonial, Brendan M. Weiss, Saad Zafar Usmani, Seema Singhal, Ajai Chari, Nizar J. Bahlis, Andrew Belch, Amrita Y. Krishnan, Robert A. Vescio, María-Victoria Mateos, Amitabha Mazumder, Robert Z. Orlowski, Heather J Sutherland, Joan Blade, Emma Catherine Scott, Huaibao Feng, Imran Khan, Clarissa M. Uhlar, Tahamtan Ahmadi, Peter Michael Voorhees. Phase II study of daratumumab (DARA) monotherapy in patients with ≥ 3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius). 2015 ASCO Annual Meeting abstract LBA8512. [http://meetinglibrary.asco.org/content/150339-156 link to abstract] -->
 
−
# '''SIRIUS:''' Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, Belch A, Krishnan A, Vescio RA, Mateos MV, Mazumder A, Orlowski RZ, Sutherland HJ, Bladé J, Scott EC, Oriol A, Berdeja J, Gharibo M, Stevens DA, LeBlanc R, Sebag M, Callander N, Jakubowiak A, White D, de la Rubia J, Richardson PG, Lisby S, Feng H, Uhlar CM, Khan I, Ahmadi T, Voorhees PM. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016 Apr 9;387(10027):1551-60. Epub 2016 Jan 7. [https://doi.org/10.1016/s0140-6736(15)01120-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26778538 PubMed] NCT01985126
 
−
## '''Pooled update:''' Usmani SZ, Weiss BM, Plesner T, Bahlis NJ, Belch A, Lonial S, Lokhorst HM, Voorhees PM, Richardson PG, Chari A, Sasser AK, Axel A, Feng H, Uhlar CM, Wang J, Khan I, Ahmadi T, Nahi H. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood. 2016 Jul 7;128(1):37-44. Epub 2016 May 23. [http://www.bloodjournal.org/content/128/1/37.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937359/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27216216 PubMed]
 
−
## '''Pooled update:''' Usmani SZ, Nahi H, Plesner T, Weiss BM, Bahlis NJ, Belch A, Voorhees PM, Laubach JP, van de Donk NWCJ, Ahmadi T, Uhlar CM, Wang J, Feng H, Qi M, Richardson PG, Lonial S. Daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma: final results from the phase 2 GEN501 and SIRIUS trials. Lancet Haematol. 2020 Jun;7(6):e447-e455. [https://doi.org/10.1016/s2352-3026(20)30081-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32470437/ PubMed]
 
−
#'''COLUMBA:''' Mateos MV, Nahi H, Legiec W, Grosicki S, Vorobyev V, Spicka I, Hungria V, Korenkova S, Bahlis N, Flogegard M, Bladé J, Moreau P, Kaiser M, Iida S, Laubach J, Magen H, Cavo M, Hulin C, White D, De Stefano V, Clemens PL, Masterson T, Lantz K, O'Rourke L, Heuck C, Qin X, Parasrampuria DA, Yuan Z, Xu S, Qi M, Usmani SZ. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020 May;7(5):e370-e380. Epub 2020 Mar 23. [https://doi.org/10.1016/s2352-3026(20)30070-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32213342 PubMed] NCT03277105
 
−
##'''Update:''' Usmani SZ, Nahi H, Legiec W, Grosicki S, Vorobyev V, Spicka I, Hungria V, Korenkova S, Bahlis NJ, Flogegard M, Bladé J, Moreau P, Kaiser M, Iida S, Laubach J, Magen H, Cavo M, Hulin C, White D, De Stefano V, Lantz K, O'Rourke L, Heuck C, Delioukina M, Qin X, Nnane I, Qi M, Mateos MV. Final analysis of the phase 3 non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma. Haematologica. 2022 Mar 31. Epub ahead of print. [https://doi.org/10.3324/haematol.2021.279459 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35354247/ PubMed]
 
−
==Daratumumab and hyaluronidase monotherapy {{#subobject:d45623y|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:fcaub1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s2352-3026(20)30070-3 Mateos et al. 2020 (COLUMBA)]
 
−
|2017-2018
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Daratumumab_monotherapy|Daratumumab]]
 
−
| style="background-color:#eeee01" |Non-inferior ORR<br>ORR: 41% vs 37%<br>(RR 1.11, 95% CI 0.89-1.37)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*At least 3 lines of therapy including proteasome inhibitors and immunomodulatory drugs or refractory to both proteasome inhibitors and immunomodulatory drugs
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab and hyaluronidase (Darzalex Faspro)]] as follows:
 
−
**Cycles 1 & 2: 1800 mg SC once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 1800 mg SC once per day on days 1 & 15
 
−
**Cycle 7 onwards: 1800 mg SC once on day 1
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''COLUMBA:''' Mateos MV, Nahi H, Legiec W, Grosicki S, Vorobyev V, Spicka I, Hungria V, Korenkova S, Bahlis N, Flogegard M, Bladé J, Moreau P, Kaiser M, Iida S, Laubach J, Magen H, Cavo M, Hulin C, White D, De Stefano V, Clemens PL, Masterson T, Lantz K, O'Rourke L, Heuck C, Qin X, Parasrampuria DA, Yuan Z, Xu S, Qi M, Usmani SZ. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020 May;7(5):e370-e380. Epub 2020 Mar 23. [https://doi.org/10.1016/s2352-3026(20)30070-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32213342 PubMed] NCT03277105
 
−
##'''Update:''' Usmani SZ, Nahi H, Legiec W, Grosicki S, Vorobyev V, Spicka I, Hungria V, Korenkova S, Bahlis NJ, Flogegard M, Bladé J, Moreau P, Kaiser M, Iida S, Laubach J, Magen H, Cavo M, Hulin C, White D, De Stefano V, Lantz K, O'Rourke L, Heuck C, Delioukina M, Qin X, Nnane I, Qi M, Mateos MV. Final analysis of the phase 3 non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma. Haematologica. 2022 Mar 31. Epub ahead of print. [https://doi.org/10.3324/haematol.2021.279459 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35354247/ PubMed]
 
−
==Idecabtagene vicleucel monotherapy {{#subobject:uigh81|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b49ifj|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1817226 Raje et al. 2019 (CRB-401)]
 
−
|2016-2018
 
−
|style="background-color:#91cf61"|Phase 1, >20 pts
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2024850 Munshi et al. 2021 (KarMMa)]
 
−
|2017-2018
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|Awaiting publication (KarMMa-3)
 
−
|2019-2026
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|Investigator's choice of:<br>1. [[#Dara-Pd|Dara-Pd]]<br>2. [[#Dara-Vd|Dara-Vd]]<br>3. [[#IRd|IRd]]<br>4. [[#Carfilzomib_.26_Dexamethasone_.28Kd.29|Kd]]<br>5. [[#Elo-Pd|Elo-Pd]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Idecabtagene vicleucel (Abecma)]]
 
−
</div></div>
 
−
===References===
 
−
# '''CRB-401:''' Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, Liedtke M, Rosenblatt J, Maus MV, Turka A, Lam LP, Morgan RA, Friedman K, Massaro M, Wang J, Russotti G, Yang Z, Campbell T, Hege K, Petrocca F, Quigley MT, Munshi N, Kochenderfer JN. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019 May 2;380(18):1726-1737. [https://doi.org/10.1056/NEJMoa1817226 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31042825 PubMed] NCT02658929
 
−
# '''KarMMa:''' Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, Raje N, Lin Y, Siegel D, Oriol A, Moreau P, Yakoub-Agha I, Delforge M, Cavo M, Einsele H, Goldschmidt H, Weisel K, Rambaldi A, Reece D, Petrocca F, Massaro M, Connarn JN, Kaiser S, Patel P, Huang L, Campbell TB, Hege K, San-Miguel J. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021 Feb 25;384(8):705-716. [https://doi.org/10.1056/nejmoa2024850 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33626253/ PubMed] NCT03361748
 
−
#'''KarMMa-3:''' NCT03651128
 
−
==Ixazomib monotherapy {{#subobject:3fe8c1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, bi-weekly, 2 out of 3 weeks {{#subobject:b49446|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574453/ Richardson et al. 2014 (C16003)]
 
−
|2009-2012
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|-
 
−
|}
 
−
''Note: this is the dosing used in the expansion cohort.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ixazomib (Ninlaro)]] 2 mg/m<sup>2</sup> PO once per day on days 1, 4, 8, 11
 
−
'''21-day cycle for up to 12 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 3 out of 4 weeks {{#subobject:37950f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558585/ Kumar et al. 2015 (MC1181)]
 
−
|2012
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*At least 1 prior line of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ixazomib (Ninlaro)]] 5.5 mg PO once per day on days 1, 8, 15
 
−
'''28-day cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with no minor response by end of cycle 2, no PR by end of cycle 4, or progression: [[#Ixazomib_.26_Dexamethasone|Ixazomib & Dexamethasone]]
 
−
</div></div>
 
−
===References===
 
−
# '''C16003:''' Richardson PG, Baz R, Wang M, Jakubowiak AJ, Laubach JP, Harvey RD, Talpaz M, Berg D, Liu G, Yu J, Gupta N, Di Bacco A, Hui AM, Lonial S. Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma patients. Blood. 2014 Aug 14;124(7):1038-46. Epub 2014 Jun 11. [http://www.bloodjournal.org/content/124/7/1038.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574453/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24920586 PubMed] NCT00932698
 
−
# '''MC1181:''' Kumar SK, LaPlant B, Roy V, Reeder CB, Lacy MQ, Gertz MA, Laumann K, Thompson MA, Witzig TE, Buadi FK, Rivera CE, Mikhael JR, Bergsagel PL, Kapoor P, Hwa L, Fonseca R, Stewart AK, Chanan-Khan A, Rajkumar SV, Dispenzieri A. Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib. Blood Cancer J. 2015 Aug 14;5:e338. [https://doi.org/10.1038/bcj.2015.60 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558585/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26275080 PubMed] NCT01415882
 
−
## '''Update:''' Kumar SK, LaPlant BR, Reeder CB, Roy V, Halvorson AE, Buadi F, Gertz MA, Bergsagel PL, Dispenzieri A, Thompson MA, Crawley J, Kapoor P, Mikhael J, Stewart K, Hayman SR, Hwa YL, Gonsalves W, Witzig TE, Ailawadhi S, Dingli D, Go RS, Lin Y, Rivera CE, Rajkumar SV, Lacy MQ. Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib. Blood. 2016 Nov 17;128(20):2415-2422. [https://doi.org/10.1182/blood-2016-05-717769 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114487/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27702799 PubMed]
 
−
==Lenalidomide monotherapy {{#subobject:ea18d8|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:96b9ec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895441/ Richardson et al. 2006]
 
−
|2002-2003
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic)
 
−
|[[#Lenalidomide_monotherapy|Lenalidomide]]; 15 mg PO twice per day
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|[http://www.bloodjournal.org/content/114/4/772.long Richardson et al. 2009 (CC-5013-MM-014)]
 
−
|2003-2004
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|}
 
−
''Note: This regimen is essentially of historical interest, as neither dosing of lenalidomide is in common use now.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 30 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Richardson et al. 2006, patients with SD or progression after 2 cycles: Escalation to [[#Lenalidomide_.26_Dexamethasone_.28Rd.29_3|Rd]]
 
−
</div></div>
 
−
===References===
 
−
# Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M, Schlossman RL, Rajkumar SV, Desikan KR, Hideshima T, Munshi NC, Kelly-Colson K, Doss D, McKenney ML, Gorelik S, Warren D, Freeman A, Rich R, Wu A, Olesnyckyj M, Wride K, Dalton WS, Zeldis J, Knight R, Weller E, Anderson KC. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood. 2006 Nov 15;108(10):3458-64. Epub 2006 Jul 13. [http://www.bloodjournal.org/content/108/10/3458.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895441/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16840727 PubMed]
 
−
# '''CC-5013-MM-014:''' Richardson P, Jagannath S, Hussein M, Berenson J, Singhal S, Irwin D, Williams SF, Bensinger W, Badros AZ, Vescio R, Kenvin L, Yu Z, Olesnyckyj M, Zeldis J, Knight R, Anderson KC. Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood. 2009 Jul 23;114(4):772-8. Epub 2009 May 26. [http://www.bloodjournal.org/content/114/4/772.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19471019 PubMed] NCT00065351
 
−
==Pomalidomide monotherapy {{#subobject:0e409f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a946bf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962162/ Richardson et al. 2014 (CC-4047-MM-002)]
 
−
|2009-NR
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (C)
 
−
|[[#Pomalidomide_.26_Dexamethasone_.28Pd.29|Pd]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*At least 2 lines of therapy including lenalidomide and bortezomib
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 81 to 100 mg PO once per day (unless contraindicated)
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''CC-4047-MM-002:''' Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, Chen C, Lonial S, Jakubowiak A, Bahlis N, Song K, Belch A, Raje N, Shustik C, Lentzsch S, Lacy M, Mikhael J, Matous J, Vesole D, Chen M, Zaki MH, Jacques C, Yu Z, Anderson K. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014 Mar 20;123(12):1826-32. Epub 2014 Jan 13. Erratum in: Blood. 2014 May 15;123(20):3208-9. [http://www.bloodjournal.org/content/123/12/1826.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962162/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24421329 PubMed] NCT00833833
 
−
==Thalidomide monotherapy {{#subobject:ff02e1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:43a4e3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199911183412102 Singhal et al. 1999]
 
−
|1997-1998
 
−
|style="background-color:#91cf61"|Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Thalidomide (Thalomid)]] 200 mg PO once per day, increased by 200 mg every two weeks for six weeks, to final dose of 800 mg per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeldis J, Siegel D, Crowley J, Barlogie B. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999 Nov 18;341(21):1565-71. Erratum in: N Engl J Med 2000 Feb 3;342(5):364. [https://doi.org/10.1056/NEJM199911183412102 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10564685 PubMed]
 
−
# Yakoub-Agha I, Mary JY, Hulin C, Doyen C, Marit G, Benboubker L, Voillat L, Moreau P, Berthou C, Stoppa AM, Maloisel F, Rodon P, Dib M, Pegourie B, Casassus P, Slama B, Damaj G, Zerbib R, Harousseau JL, Mohty M, Facon T; Intergroupe Francophone du Myélome (IFM). Low-dose vs. high-dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome. Eur J Haematol. 2012 Mar;88(3):249-59. Epub 2012 Jan 4. [https://doi.org/10.1111/j.1600-0609.2011.01729.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/22023551/ PubMed]
 
−
==Vemurafenib monotherapy {{#subobject:c957e9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5b6425|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ Hyman et al. 2015 (VE-BASKET)]
 
−
|2012-2014
 
−
|style="background-color:#ffffbe"|Basket trial, <20 pts in subgroup
 
−
|-
 
−
|}
 
−
''Note: Andrulis et al. 2013 is a single patient case report with a good response. Sharman et al. reports two patients with good response. In the Hyman et al. 2015 trial, there were 5 patients with multiple myeloma; "No patients with multiple myeloma have had a response to date."''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Vemurafenib (Zelboraf)]] 960 mg PO twice per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''Case report:''' Andrulis M, Lehners N, Capper D, Penzel R, Heining C, Huellein J, Zenz T, von Deimling A, Schirmacher P, Ho AD, Goldschmidt H, Neben K, Raab MS. Targeting the BRAF V600E mutation in multiple myeloma. Cancer Discov. 2013 Aug;3(8):862-9. Epub 2013 Apr 23. [http://cancerdiscovery.aacrjournals.org/content/3/8/862.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23612012 PubMed]
 
−
# '''Case series:''' Sharman JP, Chmielecki J, Morosini D, Palmer GA, Ross JS, Stephens PJ, Stafl J, Miller VA, Ali SM. Vemurafenib response in 2 patients with posttransplant refractory BRAF V600E-mutated multiple myeloma. Clin Lymphoma Myeloma Leuk. 2014 Oct;14(5):e161-3. Epub 2014 Jun 11. [https://doi.org/10.1016/j.clml.2014.06.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24997557 PubMed]
 
−
# '''VE-BASKET:''' Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015 Aug 20;373(8):726-36. [https://doi.org/10.1056/NEJMoa1502309 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26287849 PubMed] NCT01524978
 
−
==Venetoclax monotherapy {{#subobject:cjguzb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1ughz25|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1182/blood-2017-06-788786 Kumar et al. 2017 (M13-367)]
 
−
|2012-NR
 
−
| style="background-color:#91cf61" |Phase 1, >20 pts in this cohort
 
−
|-
 
−
|}
 
−
''Note: This is the safety expansion cohort dosing.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*t(11;14)
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Venetoclax (Venclexta)]] as follows:
 
−
**Week -2 (lead-in): 400 mg PO once per day
 
−
**Week -1 (lead-in): 800 mg PO once per day
 
−
**Cycle 1 onwards: 1200 mg PO once per day
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''M13-367:''' Kumar S, Kaufman JL, Gasparetto C, Mikhael J, Vij R, Pegourie B, Benboubker L, Facon T, Amiot M, Moreau P, Punnoose EA, Alzate S, Dunbar M, Xu T, Agarwal SK, Enschede SH, Leverson JD, Ross JA, Maciag PC, Verdugo M, Touzeau C. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood. 2017 Nov 30;130(22):2401-2409. Epub 2017 Oct 10. [https://doi.org/10.1182/blood-2017-06-788786 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29018077/ PubMed] NCT01794520
 
−
=Relapsed or refractory, doublets=
 
−
==Bortezomib & Dexamethasone (Vd) {{#subobject:899402|Regimen=1}}==
 
−
Vd: '''<u>V</u>'''elcade (Bortezomib) & low-dose '''<u>d</u>'''examethasone
 
−
<br>BD: '''<u>B</u>'''ortezomib & '''<u>D</u>'''examethasone
 
−
<br>Bd: '''<u>B</u>'''ortezomib & low-dose '''<u>d</u>'''examethasone
 
−
<br>Bort-Dex: '''<u>Bort</u>'''ezomib & '''<u>Dex</u>'''amethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, indefinite 21-day then 28-day cycles {{#subobject:a29ce5 |Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900953/ Jakubowiak et al. 2016 (CA204-009)]
 
−
|2012-2013
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (C)
 
−
|[[#Elo-Vd|Elo-Vd]]
 
−
|style="background-color:#fee08b"|Might have inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(20)30525-8 Kumar et al. 2020 (BELLINI)]
 
−
|2016-2017
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29_.26_Venetoclax_99|Vd & Venetoclax]]
 
−
|style="background-color:#d73027"|Inferior PFS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Despite meeting the primary endpoint, there was increased mortality in the experimental group, due to increased infections.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*CA204-009 & BELLINI: 1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] as follows:
 
−
**Cycles 1 to 8: 1.3 mg/m<sup>2</sup> IV or SC once per day on days 1, 4, 8, 11
 
−
**Cycle 9 onwards: 1.3 mg/m<sup>2</sup> IV or SC once per day on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 8: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
**Cycle 9 onwards: 20 mg PO once per day on days 1, 2, 8, 9, 15, 16
 
−
'''21-day cycle for 8 cycles, then 28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, SC 21-day cycles (8 total) {{#subobject:c5b78f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(11)70081-X Moreau et al. 2011 (MMY-3021)]
 
−
|2008-2010
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Bort-Dex]]; IV
 
−
|style="background-color:#eeee01"|Non-inferior ORR<br>ORR: 42% vs 42%
 
−
|-
 
−
|[https://doi.org/10.1111/ejh.12937 Terpos et al. 2017 (OPTIMRETREAT)]
 
−
|2013-2016
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Bort-Dex]] x 6, then bortezomib maint.
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1606038 Palumbo et al. 2016 (CASTOR)]
 
−
|2014-2015
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Dara-Vd|Dara-Vd]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: In MMY-3021, patients who were "evolving" towards CR after 8 cycles could receive 2 additional cycles.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*MMY-3021: 1 to 3 prior lines of therapy
 
−
*CASTOR: At least 1 prior line of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*MMY-3021: [[Multiple_myeloma_-_historical#Bortezomib_monotherapy|Bortezomib]] x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> SC once per day on days 1, 4, 8, 11
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
'''21-day cycle for 8 cycles (see note)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
  
−
===Regimen variant #3, IV 21-day cycles (16 total) {{#subobject:c68433|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70440-1 San-Miguel et al. 2014 (PANORAMA 1)]
 
−
|2010-2012
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29_.26_Panobinostat|Vd & Panobinostat]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: Patients who had clinical benefit per the modified European Group for Blood and Marrow Transplantation [EBMT] criteria on day 1 of cycle 8 proceeded to the last 8 cycles.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] as follows:
 
−
**Cycles 1 to 8: 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
**Cycles 9 to 16: 1.3 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 8: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
**Cycles 9 to 16: 20 mg PO once per day on days 1, 2, 8, 9
 
−
'''21-day cycle for 16 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 21-day cycles, response-adapted {{#subobject:47b011|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492844/ Hjorth et al. 2012 (NMSG 17/07)]
 
−
|2007-2010
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
−
|[[#Thalidomide_.26_Dexamethasone_.28TD.29|Thal-Dex]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729908/ Dimopoulos et al. 2013 (CR013165)]
 
−
|2008-2009
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|style="background-color:#d3d3d3"|Not evaluable
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*NMSG 17/07: Failure of melphalan with no prior exposure to bortezomib or thalidomide
 
−
*CR013165: 1 prior line of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
====Supportive therapy====
 
−
*"Antithrombotic prophylaxis and [[Acyclovir (Zovirax)|acyclovir]] prophylaxis were not mandatory according to the study protocol but used routinely in an increasing proportion of participating centers during the study period."
 
−
'''21-day cycles until progression or best response, which would then be followed by 1 to 2 additional cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, IV 21-day cycles (8 total) {{#subobject:5d8a03|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2004.05188.x Jagannath et al. 2004 (CREST)]
 
−
|2001-2002
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Bort-Dex]]; low-dose
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(11)70081-X Moreau et al. 2011 (MMY-3021)]
 
−
|2008-2010
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Bort-Dex]]; SC
 
−
|style="background-color:#eeee01"|Non-inferior ORR
 
−
|-
 
−
|[https://doi.org/10.1007/s00277-017-3065-z Kropff et al. 2017 (CR015247)]
 
−
|2008-2010
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#VDC|VCD]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
''Note: In MMY-3021, patients who were "evolving" towards CR after 8 cycles could receive 2 additional cycles.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*CREST: Failure of frontline chemotherapy
 
−
*MMY-3021 & CR015247: 1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*CREST: [[Multiple_myeloma_-_historical#Bortezomib_monotherapy|Bortezomib]] x 2 to 4 cycles
 
−
*MMY-3021: [[Multiple_myeloma_-_historical#Bortezomib_monotherapy|Bortezomib]] x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 8, 11
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
'''21-day cycle for 8 cycles (see note)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
 
−
===Regimen variant #6, low-dose IV 21-day cycles (8 total) {{#subobject:823e44|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2004.05188.x Jagannath et al. 2004 (CREST)]
 
−
|2001-2002
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-de-esc)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Bort-Dex]]; standard-dose
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*CREST: Failure of frontline chemotherapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Multiple_myeloma_-_historical#Bortezomib_monotherapy|Bortezomib]] x 2 to 4 cycles
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 8, 11
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #7, IV indefinite 21-day cycles {{#subobject:0e7bc2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa030288 Richardson et al. 2003 (SUMMIT)]
 
−
|2001
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#8c6bb1" |RR: 35%
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00464-7 Dimopoulos et al. 2015 (ENDEAVOR)]
 
−
|2012-2014
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Carfilzomib_.26_Dexamethasone_.28Kd.29|Kd]]
 
−
| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for ENDEAVOR is based on the 2019 update.''<br>
 
−
''Note: SUMMIT & MMY-3001 specified a total of 8 cycles, but those who were deriving clinical benefit could continue beyond this.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*ENDEAVOR: 1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*SUMMIT & MMY-3001: [[Multiple_myeloma_-_historical#Bortezomib_monotherapy|Bortezomib]] x 2 to 4 cycles
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 8, 11
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #8, SC indefinite 21-day cycles {{#subobject:6696bc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00464-7 Dimopoulos et al. 2015 (ENDEAVOR)]
 
−
|2012-2014
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Carfilzomib_.26_Dexamethasone_.28Kd.29|Kd]]
 
−
| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for ENDEAVOR is based on the 2019 update.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*ENDEAVOR: 1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> SC once per day on days 1, 4, 8, 11
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #9, SC indefinite 21-day then 35-day cycles {{#subobject:6696bc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(20)32292-3 Grosicki et al. 2020 (BOSTON)]
 
−
|2017-2019
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#SVd|SVd]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*1 to 3 prior lines of therapy, including proteasome inhibitors
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] as follows:
 
−
**Cycles 1 to 8: 1.3 mg/m<sup>2</sup> SC once per day on days 1, 4, 8, 11
 
−
**Cycle 9 onwards: 1.3 mg/m<sup>2</sup> SC once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 8: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
**Cycle 9 onwards: 20 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23, 29, 30
 
−
'''21-day cycle for 8 cycles, then 35-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #10, indefinite 35-day cycles {{#subobject:ed7a2d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[http://ar.iiarjournals.org/content/31/6/2297.long Fukushima et al. 2011]
 
−
|2007-2010
 
−
| style="background-color:#ffffbe" |Retrospective
 
−
| style="background-color:#e0ecf4" |ORR: 77%
 
−
|-
 
−
|}
 
−
''Note: treatment could be stopped if CR was achieved.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
'''35-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''SUMMIT:''' Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003 Jun 26;348(26):2609-17. [https://doi.org/10.1056/NEJMoa030288 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12826635 PubMed]
 
−
## '''Subgroup analysis:''' Jagannath S, Richardson PG, Barlogie B, Berenson JR, Singhal S, Irwin D, Srkalovic G, Schenkein DP, Esseltine DL, Anderson KC; SUMMIT/CREST Investigators. Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Haematologica. 2006 Jul;91(7):929-34. [http://www.haematologica.org/content/91/7/929.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16818280 PubMed]
 
−
## '''Pooled subgroup analysis:''' Jagannath S, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Cowan JM, Anderson KC. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia. 2007 Jan;21(1):151-7. Epub 2006 Nov 9. [https://www.nature.com/articles/2404442 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17096017 PubMed]
 
−
# '''CREST:''' Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Adams J, Kauffman M, Esseltine DL, Schenkein DP, Anderson KC. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004 Oct;127(2):165-72. [https://doi.org/10.1111/j.1365-2141.2004.05188.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15461622 PubMed]
 
−
## '''Subgroup Analysis:''' Jagannath S, Richardson PG, Barlogie B, Berenson JR, Singhal S, Irwin D, Srkalovic G, Schenkein DP, Esseltine DL, Anderson KC; SUMMIT/CREST Investigators. Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Haematologica. 2006 Jul;91(7):929-34. [http://www.haematologica.org/content/91/7/929.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16818280 PubMed]
 
−
## '''Update:''' Jagannath S, Barlogie B, Berenson JR, Siegel DS, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Esseltine DL, Anderson KC. Updated survival analyses after prolonged follow-up of the phase 2, multicenter CREST study of bortezomib in relapsed or refractory multiple myeloma. Br J Haematol. 2008 Nov;143(4):537-40. Epub 2008 Sep 6. [https://doi.org/10.1111/j.1365-2141.2008.07359.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/18783399 PubMed]
 
−
# '''MMY-3001:''' Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hajek R, Spencer A, San Miguel J, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Zhuang SH, Parekh T, Xiu L, Yuan Z, Rackoff W, Harousseau JL. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007 Sep 1;25(25):3892-901. Epub 2007 Aug 6. [https://doi.org/10.1200/jco.2006.10.5460 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17679727 PubMed] NCT00103506
 
−
## '''Update:''' Mikhael JR, Belch AR, Prince HM, Lucio MN, Maiolino A, Corso A, Petrucci MT, Musto P, Komarnicki M, Stewart AK. High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program. Br J Haematol. 2009 Jan;144(2):169-75. Epub 2008 Nov 19. [https://doi.org/10.1111/j.1365-2141.2008.07409.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19036114 PubMed]
 
−
## '''Update:''' Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hajek R, Spencer A, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Xiu L, Cakana A, Parekh T, San-Miguel JF. Final overall survival results of a randomized trial comparing bortezomib plus pegylated liposomal doxorubicin with bortezomib alone in patients with relapsed or refractory multiple myeloma. Cancer. 2016 Jul 1;122(13):2050-6. Epub 2016 May 18. [https://doi.org/10.1002/cncr.30026 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5701574/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27191689 PubMed]
 
−
# '''MMY-3021:''' Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M, Rekhtman G, Masliak Z, Robak T, Shubina A, Arnulf B, Kropff M, Cavet J, Esseltine DL, Feng H, Girgis S, van de Velde H, Deraedt W, Harousseau JL. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011 May;12(5):431-40. Epub 2011 Apr 18. [https://doi.org/10.1016/S1470-2045(11)70081-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21507715 PubMed] NCT00722566
 
−
## '''Update:''' Arnulf B, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, van de Velde H, Feng H, Cakana A, Deraedt W, Moreau P. Updated survival analysis of a randomized phase III study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma. Haematologica. 2012 Dec;97(12):1925-8. Epub 2012 Jun 11. [http://www.haematologica.org/content/97/12/1925.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685287/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22689676 PubMed]
 
−
## '''Subgroup analysis:''' Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Rekhtman G, Masliak Z, Robak P, Esseltine DL, Feng H, Deraedt W, van de Velde H, Arnulf B. Subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma: subanalysis of patients with renal impairment in the phase III MMY-3021 study. Haematologica. 2015 May;100(5):e207-10. Epub 2015 Jan 16. [http://www.haematologica.org/content/100/5/e207.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420234/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25596270 PubMed]
 
−
# '''Retrospective:''' Fukushima T, Nakamura T, Iwao H, Nakajima A, Miki M, Sato T, Sakai T, Sawaki T, Fujita Y, Tanaka M, Masaki Y, Nakajima H, Motoo Y, Umehara H. Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Anticancer Res. 2011 Jun;31(6):2297-302. [http://ar.iiarjournals.org/content/31/6/2297.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21737655 PubMed]
 
−
# '''NMSG 17/07:''' Hjorth M, Hjertner Ø, Knudsen LM, Gulbrandsen N, Holmberg E, Pedersen PT, Andersen NF, Andréasson B, Billström R, Carlson K, Carlsson MS, Flogegård M, Forsberg K, Gimsing P, Karlsson T, Linder O, Nahi H, Othzén A, Swedin A; Nordic Myeloma Study Group. Thalidomide and dexamethasone vs bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study. Eur J Haematol. 2012 Jun;88(6):485-96. Epub 2012 Mar 30. [https://doi.org/10.1111/j.1600-0609.2012.01775.x link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492844/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22404182 PubMed] NCT00602511
 
−
# '''CR013165:''' Dimopoulos MA, Beksac M, Benboubker L, Roddie H, Allietta N, Broer E, Couturier C, Mazier MA, Angermund R, Facon T. Phase 2 study of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide for sub-optimal response as second-line treatment for patients with multiple myeloma. Haematologica. 2013 Aug;98(8):1264-72. Epub 2013 May 28. [http://www.haematologica.org/content/98/8/1264.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729908/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23716559 PubMed] NCT00908232
 
−
<!-- Presented in abstract form at the American Society of Hematology Annual Meeting, Atlanta, GA, December 8-11, 2012. -->
 
−
# '''PANORAMA 1:''' San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Günther A, Nakorn TN, Siritanaratkul N, Corradini P, Chuncharunee S, Lee JJ, Schlossman RL, Shelekhova T, Yong K, Tan D, Numbenjapon T, Cavenagh JD, Hou J, LeBlanc R, Nahi H, Qiu L, Salwender H, Pulini S, Moreau P, Warzocha K, White D, Bladé J, Chen W, de la Rubia J, Gimsing P, Lonial S, Kaufman JL, Ocio EM, Veskovski L, Sohn SK, Wang MC, Lee JH, Einsele H, Sopala M, Corrado C, Bengoudifa BR, Binlich F, Richardson PG. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1195-206. Epub 2014 Sep 18. Erratum in: Lancet Oncol. 2015 Jan;16(1):e6. [https://doi.org/10.1016/S1470-2045(14)70440-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25242045 PubMed] NCT01023308
 
−
## '''Subgroup analysis:''' Richardson PG, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Guenther A, Nakorn TN, Siritanaratkul N, Schlossman RL, Hou J, Moreau P, Lonial S, Lee JH, Einsele H, Sopala M, Bengoudifa BR, Corrado C, Binlich F, San-Miguel JF. Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment. Blood. 2016 Feb 11;127(6):713-21. Epub 2015 Dec 2. [http://www.bloodjournal.org/content/127/6/713.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760132/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26631116 PubMed]
 
−
## '''Update:''' San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Günther A, Nakorn TN, Siritanaratkul N, Schlossman RL, Hou J, Moreau P, Lonial S, Lee JH, Einsele H, Sopala M, Bengoudifa BR, Binlich F, Richardson PG. Overall survival of patients with relapsed multiple myeloma treated with panobinostat or placebo plus bortezomib and dexamethasone (the PANORAMA 1 trial): a randomised, placebo-controlled, phase 3 trial. Lancet Haematol. 2016 Nov;3(11):e506-e515. Epub 2016 Oct 14. [https://doi.org/10.1016/S2352-3026(16)30147-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27751707 PubMed]
 
−
# '''ENDEAVOR:''' Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hájek R, Facon T, Ludwig H, Oriol A, Goldschmidt H, Rosiñol L, Straub J, Suvorov A, Araujo C, Rimashevskaya E, Pika T, Gaidano G, Weisel K, Goranova-Marinova V, Schwarer A, Minuk L, Masszi T, Karamanesht I, Offidani M, Hungria V, Spencer A, Orlowski RZ, Gillenwater HH, Mohamed N, Feng S, Chng WJ; ENDEAVOR investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016 Jan;17(1):27-38. Epub 2015 Dec 5. [https://doi.org/10.1016/S1470-2045(15)00464-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26671818 PubMed] NCT01568866
 
−
## '''Subgroup analysis:''' Chng WJ, Goldschmidt H, Dimopoulos MA, Moreau P, Joshua D, Palumbo A, Facon T, Ludwig H, Pour L, Niesvizky R, Oriol A, Rosiñol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Gillenwater HH, Mohamed N, Feng S, Aggarwal S, Hájek R. Carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed or refractory multiple myeloma by cytogenetic risk in the phase 3 study ENDEAVOR. Leukemia. 2017 Jun;31(6):1368-1374. Epub 2016 Dec 27. [https://www.nature.com/articles/leu2016390 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467042/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28025582 PubMed]
 
−
## '''Update:''' Dimopoulos MA, Goldschmidt H, Niesvizky R, Joshua D, Chng WJ, Oriol A, Orlowski RZ, Ludwig H, Facon T, Hajek R, Weisel K, Hungria V, Minuk L, Feng S, Zahlten-Kumeli A, Kimball AS, Moreau P. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1327-1337. Epub 2017 Aug 23. [https://doi.org/10.1016/S1470-2045(17)30578-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28843768 PubMed]
 
−
## '''Update:''' Orlowski RZ, Moreau P, Niesvizky R, Ludwig H, Oriol A, Chng WJ, Goldschmidt H, Yang Z, Kimball AS, Dimopoulos M. Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Overall Survival, Safety, and Subgroups. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):522-530.e1. Epub 2019 May 2. [https://doi.org/10.1016/j.clml.2019.04.018 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31160237 PubMed]
 
−
# '''CA204-009:''' Jakubowiak A, Offidani M, Pégourie B, De La Rubia J, Garderet L, Laribi K, Bosi A, Marasca R, Laubach J, Mohrbacher A, Carella AM, Singhal AK, Tsao LC, Lynch M, Bleickardt E, Jou YM, Robbins M, Palumbo A. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood. 2016 Jun 9;127(23):2833-40. Epub 2016 Apr 18. [http://www.bloodjournal.org/content/127/23/2833.long link to original article] '''contains dosing details in supplement''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900953/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27091875 PubMed] NCT01478048
 
−
<!-- # ASCO 2016 Abstract LBA4 -->
 
−
# '''CASTOR:''' Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Qi M, Schecter J, Amin H, Qin X, Deraedt W, Ahmadi T, Spencer A, Sonneveld P; CASTOR Investigators. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016 Aug 25;375(8):754-66. [https://doi.org/10.1056/NEJMoa1606038 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1606038/suppl_file/nejmoa1606038_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27557302 PubMed] NCT02136134
 
−
## '''Update:''' Spencer A, Lentzsch S, Weisel K, Avet-Loiseau H, Mark TM, Spicka I, Masszi T, Lauri B, Levin MD, Bosi A, Hungria V, Cavo M, Lee JJ, Nooka AK, Quach H, Lee C, Barreto W, Corradini P, Min CK, Scott EC, Chanan-Khan AA, Horvath N, Capra M, Beksac M, Ovilla R, Jo JC, Shin HJ, Sonneveld P, Soong D, Casneuf T, Chiu C, Amin H, Qi M, Thiyagarajah P, Sasser AK, Schecter JM, Mateos MV. Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Haematologica. 2018 Dec;103(12):2079-87. Epub 2018 Sep 20. [http://www.haematologica.org/content/103/12/2079 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6269293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30237264 PubMed]
 
−
## '''Update:''' Mateos MV, Sonneveld P, Hungria V, Nooka AK, Estell JA, Barreto W, Corradini P, Min CK, Medvedova E, Weisel K, Chiu C, Schecter JM, Amin H, Qin X, Ukropec J, Kobos R, Spencer A. Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR. Clin Lymphoma Myeloma Leuk. 2020 Aug;20(8):509-518. Epub 2019 Oct 9. [https://doi.org/10.1016/j.clml.2019.09.623 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32482541/ PubMed]
 
−
# '''CR015247:''' Kropff M, Vogel M, Bisping G, Schlag R, Weide R, Knauf W, Fiechtner H, Kojouharoff G, Kremers S, Berdel WE. Bortezomib and low-dose dexamethasone with or without continuous low-dose oral cyclophosphamide for primary refractory or relapsed multiple myeloma: a randomized phase III study. Ann Hematol. 2017 Nov;96(11):1857-1866. Epub 2017 Sep 14. [https://doi.org/10.1007/s00277-017-3065-z link to original article] [https://pubmed.ncbi.nlm.nih.gov/28905189 PubMed] NCT00813150
 
−
# '''OPTIMRETREAT:''' Terpos E, Gobbi M, Potamianou A, Lahaye M, Couturier C, Cavo M. Retreatmentvand prolonged therapy with subcutaneous bortezomib in patients with relapsed multiple myeloma: a randomized, controlled, phase III study. Eur J Haematol. 2018 Jan;100(1):10-19. Epub 2017 Oct 30. [https://doi.org/10.1111/ejh.12937 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28801967 PubMed] NCT01910987
 
−
# '''BELLINI:''' Kumar SK, Harrison SJ, Cavo M, de la Rubia J, Popat R, Gasparetto C, Hungria V, Salwender H, Suzuki K, Kim I, Punnoose EA, Hong WJ, Freise KJ, Yang X, Sood A, Jalaluddin M, Ross JA, Ward JE, Maciag PC, Moreau P. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2020 Dec;21(12):1630-1642. Epub 2020 Oct 29. [https://doi.org/10.1016/s1470-2045(20)30525-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33129376/ PubMed] NCT02755597
 
−
# '''BOSTON:''' Grosicki S, Simonova M, Spicka I, Pour L, Kriachok I, Gavriatopoulou M, Pylypenko H, Auner HW, Leleu X, Doronin V, Usenko G, Bahlis NJ, Hajek R, Benjamin R, Dolai TK, Sinha DK, Venner CP, Garg M, Gironella M, Jurczyszyn A, Robak P, Galli M, Wallington-Beddoe C, Radinoff A, Salogub G, Stevens DA, Basu S, Liberati AM, Quach H, Goranova-Marinova VS, Bila J, Katodritou E, Oliynyk H, Korenkova S, Kumar J, Jagannath S, Moreau P, Levy M, White D, Gatt ME, Facon T, Mateos MV, Cavo M, Reece D, Anderson LD Jr, Saint-Martin JR, Jeha J, Joshi AA, Chai Y, Li L, Peddagali V, Arazy M, Shah J, Shacham S, Kauffman MG, Dimopoulos MA, Richardson PG, Delimpasi S. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020 Nov 14;396(10262):1563-1573. [https://doi.org/10.1016/s0140-6736(20)32292-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33189178/ PubMed] NCT03110562
 
−
# '''BENCH:''' NCT04939142
 
−
# '''Perifosine 339:''' NCT01002248
 
−
 
−
==Bortezomib & Pegylated liposomal doxorubicin {{#subobject:2a0373|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bef7d6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.10.5460 Orlowski et al. 2007 (MMY-3001)]
 
−
|2004-2006
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[Multiple_myeloma_-_historical#Bortezomib_monotherapy|Bortezomib]]
 
−
|style="background-color:#1a9850"|Superior TTP<br>Median TTP: 9.3 vs 6.5 mo<br>(HR 0.55, 95% CI 0.43-0.71)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*1 to 3 prior lines of therapy, not including bortezomib
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 8, 11
 
−
====Chemotherapy====
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 30 mg/m<sup>2</sup> IV over at least 1 hour once on day 4, '''given second'''
 
−
====Supportive therapy====
 
−
*[[:Category:Bisphosphonates|Bisphosphonates]] were used according to established guidelines
 
−
'''21-day cycle for 8 or more cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MMY-3001:''' Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hajek R, Spencer A, San Miguel J, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Zhuang SH, Parekh T, Xiu L, Yuan Z, Rackoff W, Harousseau JL. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007 Sep 1;25(25):3892-901. Epub 2007 Aug 6. [https://doi.org/10.1200/jco.2006.10.5460 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17679727 PubMed] NCT00103506
 
−
## '''Update:''' Mikhael JR, Belch AR, Prince HM, Lucio MN, Maiolino A, Corso A, Petrucci MT, Musto P, Komarnicki M, Stewart AK. High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program. Br J Haematol. 2009 Jan;144(2):169-75. Epub 2008 Nov 19. [https://doi.org/10.1111/j.1365-2141.2008.07409.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19036114 PubMed]
 
−
## '''Update:''' Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hajek R, Spencer A, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Xiu L, Cakana A, Parekh T, San-Miguel JF. Final overall survival results of a randomized trial comparing bortezomib plus pegylated liposomal doxorubicin with bortezomib alone in patients with relapsed or refractory multiple myeloma. Cancer. 2016 Jul 1;122(13):2050-6. Epub 2016 May 18. [https://doi.org/10.1002/cncr.30026 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5701574/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27191689 PubMed]
 
−
==Bortezomib & Vorinostat {{#subobject:2a5b7f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a5c93b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(13)70398-X Dimopoulos et al. 2013 (VANTAGE 088)]
 
−
|2008-2011
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Multiple_myeloma_-_historical#Bortezomib_monotherapy|Bortezomib]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 7.6 vs 6.8 mo<br>(HR 0.77, 95% CI 0.64-0.94)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 8, 11
 
−
*[[Vorinostat (Zolinza)]] 400 mg PO once per day on days 1 to 14
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''VANTAGE 088:''' Dimopoulos M, Siegel DS, Lonial S, Qi J, Hajek R, Facon T, Rosinol L, Williams C, Blacklock H, Goldschmidt H, Hungria V, Spencer A, Palumbo A, Graef T, Eid JE, Houp J, Sun L, Vuocolo S, Anderson KC. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncol. 2013 Oct;14(11):1129-1140. Epub 2013 Sep 19. [https://doi.org/10.1016/S1470-2045(13)70398-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24055414 PubMed] NCT00773747
 
−
==Carfilzomib & Dexamethasone (Kd) {{#subobject:0823d6|Regimen=1}}==
 
−
Kd: '''<u>K</u>'''yprolis (Carfilzomib) & low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 20/27 {{#subobject:9a649a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30354-1 Moreau et al. 2018 (ARROW<sub>MM</sub>)]
 
−
|2015-2016
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Carfilzomib_.26_Dexamethasone_.28Kd.29|Kd]]; weekly
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: this trial is denoted as ARROW<sub>MM</sub> to distinguish from other trials of the same name.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*2 or 3 lines of therapy, including a proteasome inhibitor and an immunomodulatory agent
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1 & 2, then 27 mg/m<sup>2</sup> IV over 10 minutes once per day on days 8, 9, 15, 16
 
−
**Cycle 2 onwards: 27 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 8: 40 mg IV or PO once per day on days 1, 8, 15, 22
 
−
**Cycle 10 onwards: 40 mg IV or PO once per day on days 1, 8, 15
 
−
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 20/56 dosing {{#subobject:9bd940|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00464-7 Dimopoulos et al. 2015 (ENDEAVOR)]
 
−
|2012-2014
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Vd]]
 
−
|style="background-color:#1a9850"|Superior OS<sup>1</sup><br>Median OS: 47.8 vs 38.8 mo<br>(HR 0.76, 95% CI 0.63-0.92)
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(21)00592-4 Moreau et al. 2021 (IKEMA)]
 
−
|2017-2019
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Isa-Kd|Isa-Kd]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for ENDEAVOR is based on the 2019 update.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*ENDEAVOR & IKEMA: 1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 2, then 56 mg/m<sup>2</sup> IV over 30 minutes once per day on days 8, 9, 15, 16
 
−
**Cycle 2 onwards: 56 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9, 15, 16
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 20/70 dosing (weekly) {{#subobject:5322cb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929927/ Berenson et al. 2016 (CHAMPION-1)]
 
−
|2012-2014
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30354-1 Moreau et al. 2018 (ARROW<sub>MM</sub>)]
 
−
|2015-2016
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
 
−
|[[#Carfilzomib_.26_Dexamethasone_.28Kd.29|Kd]]; twice-weekly
 
−
|style="background-color:#1a9850"|Superior PFS<br>Median PFS: 11.2 vs 7.6 mo<br>(HR 0.69, 95% CI 0.54-0.83)
 
−
|-
 
−
|}
 
−
''Note: this trial is denoted as ARROW<sub>MM</sub> to distinguish from other trials of the same name.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*ARROW<sub>MM</sub>: 2 or 3 lines of therapy, including a proteasome inhibitor and an immunomodulatory agent
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV over 30 minutes once on day 1, then 70 mg/m<sup>2</sup> IV over 30 minutes once per day on days 8 & 15
 
−
**Cycle 2 onwards: 70 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 8: 40 mg IV or PO once per day on days 1, 8, 15, 22
 
−
**Cycle 10 onwards: 40 mg IV or PO once per day on days 1, 8, 15
 
−
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 27 dosing {{#subobject:2b988e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740399/ Badros et al. 2013 (PX-171-005)]
 
−
|2008-2010
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Carfilzomib_monotherapy|Carfilzomib]] x 2 to 4 cycles (carfilzomib dose escalation attained during this period)
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] 27 mg/m<sup>2</sup> IV over 2 to 10 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg (route not specified) once per day on days 1, 2, 8, 9, 15, 16, '''given first'''
 
−
'''28-day cycle for 12 cycles or longer if deriving clinical benefit'''
 
−
</div></div>
 
−
===References===
 
−
# '''PX-171-005:''' Badros AZ, Vij R, Martin T, Zonder JA, Kunkel L, Wang Z, Lee S, Wong AF, Niesvizky R. Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety. Leukemia. 2013 Aug;27(8):1707-14. Epub 2013 Jan 31. [https://doi.org/10.1038/leu.2013.29 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740399/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23364621 PubMed] NCT00721734
 
−
# '''ENDEAVOR:''' Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hájek R, Facon T, Ludwig H, Oriol A, Goldschmidt H, Rosiñol L, Straub J, Suvorov A, Araujo C, Rimashevskaya E, Pika T, Gaidano G, Weisel K, Goranova-Marinova V, Schwarer A, Minuk L, Masszi T, Karamanesht I, Offidani M, Hungria V, Spencer A, Orlowski RZ, Gillenwater HH, Mohamed N, Feng S, Chng WJ; ENDEAVOR investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016 Jan;17(1):27-38. Epub 2015 Dec 5. [https://doi.org/10.1016/S1470-2045(15)00464-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26671818 PubMed] NCT01568866
 
−
## '''Subgroup analysis:''' Chng WJ, Goldschmidt H, Dimopoulos MA, Moreau P, Joshua D, Palumbo A, Facon T, Ludwig H, Pour L, Niesvizky R, Oriol A, Rosiñol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Gillenwater HH, Mohamed N, Feng S, Aggarwal S, Hájek R. Carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed or refractory multiple myeloma by cytogenetic risk in the phase 3 study ENDEAVOR. Leukemia. 2017 Jun;31(6):1368-1374. Epub 2016 Dec 27. [https://www.nature.com/articles/leu2016390 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467042/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28025582 PubMed]
 
−
## '''Update:''' Dimopoulos MA, Goldschmidt H, Niesvizky R, Joshua D, Chng WJ, Oriol A, Orlowski RZ, Ludwig H, Facon T, Hajek R, Weisel K, Hungria V, Minuk L, Feng S, Zahlten-Kumeli A, Kimball AS, Moreau P. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1327-1337. Epub 2017 Aug 23. [https://doi.org/10.1016/S1470-2045(17)30578-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28843768 PubMed]
 
−
## '''Update:''' Orlowski RZ, Moreau P, Niesvizky R, Ludwig H, Oriol A, Chng WJ, Goldschmidt H, Yang Z, Kimball AS, Dimopoulos M. Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Overall Survival, Safety, and Subgroups. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):522-530.e1. Epub 2019 May 2. [https://doi.org/10.1016/j.clml.2019.04.018 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31160237 PubMed]
 
−
# '''CHAMPION-1:''' Berenson JR, Cartmell A, Bessudo A, Lyons RM, Harb W, Tzachanis D, Agajanian R, Boccia R, Coleman M, Moss RA, Rifkin RM, Patel P, Dixon S, Ou Y, Anderl J, Aggarwal S, Berdeja JG. CHAMPION-1: a phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma. Blood. 2016 Jun 30;127(26):3360-8. Epub 2016 May 12. [http://www.bloodjournal.org/content/127/26/3360.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929927/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27207788 PubMed] NCT01677858
 
−
# '''ARROW<sub>MM</sub>:''' Moreau P, Mateos MV, Berenson JR, Weisel K, Lazzaro A, Song K, Dimopoulos MA, Huang M, Zahlten-Kumeli A, Stewart AK. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (ARROW): interim analysis results of a randomised, phase 3 study. Lancet Oncol. 2018 Jul;19(7):953-964. Epub 2018 Jun 1. Erratum in: Lancet Oncol. 2018 Aug;19(8):e382. [https://doi.org/10.1016/S1470-2045(18)30354-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29866475 PubMed] NCT02412878
 
−
#'''CANDOR:''' Dimopoulos M, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Yang H, Klippel Z, Zahlten-Kumeli A, Usmani SZ. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020 Jul 18;396(10245):186-197. [https://doi.org/10.1016/s0140-6736(20)30734-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32682484 PubMed] NCT03158688
 
−
##'''Update:''' Usmani SZ, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Gavriatopoulou M, Oriol A, Rabin N, Nooka A, Qi M, Beksac M, Jakubowiak A, Ding B, Zahlten-Kumeli A, Yusuf A, Dimopoulos M. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol. 2022 Jan;23(1):65-76. Epub 2021 Dec 3. [https://doi.org/10.1016/s1470-2045(21)00579-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34871550/ PubMed]
 
−
#'''IKEMA:''' Moreau P, Dimopoulos MA, Mikhael J, Yong K, Capra M, Facon T, Hajek R, Špička I, Baker R, Kim K, Martinez G, Min CK, Pour L, Leleu X, Oriol A, Koh Y, Suzuki K, Risse ML, Asset G, Macé S, Martin T; IKEMA study group. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021 Jun 19;397(10292):2361-2371. Epub 2021 Jun 4. [https://doi.org/10.1016/s0140-6736(21)00592-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34097854/ PubMed] NCT03275285
 
−
##'''Update:''' Martin T, Dimopoulos MA, Mikhael J, Yong K, Capra M, Facon T, Hajek R, Špička I, Casca F, Macé S, Risse ML, Moreau P. MM-064 Updated Progression-Free Survival and Depth of Response in IKEMA, a Randomized Phase 3 Trial of Isatuximab, Carfilzomib, and Dexamethasone (Isa-Kd) Versus Kd in Relapsed Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S403-S404. [https://doi.org/10.1016/s2152-2650(22)01586-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36164137/ PubMed]
 
−
#'''KarMMa-3:''' NCT03651128
 
−
==Carfilzomib & Panobinostat {{#subobject:9d99ab|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:69e42c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420216/ Berdeja et al. 2015 (SCRI MM 27)]
 
−
|2012-2013
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 45 mg/m<sup>2</sup> IV over 30 minutes once per day on days 8, 9, 15, 16
 
−
**Cycle 2 onwards: 45 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9, 15, 16
 
−
*[[Panobinostat (Farydak)]] 30 mg PO once per day on days 1, 3, 5, 15, 17, 19
 
−
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''SCRI MM 27:''' Berdeja JG, Hart LL, Mace JR, Arrowsmith ER, Essell JH, Owera RS, Hainsworth JD, Flinn IW. Phase I/II Study of the Combination of Panobinostat and Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma. Haematologica. 2015 May;100(5):670-6. Epub 2015 Feb 20. [http://www.haematologica.org/content/100/5/670 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420216/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25710456 PubMed] NCT01496118
 
−
==Cyclophosphamide & Dexamethasone {{#subobject:2c713a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5a653e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220126/ Hájek et al. 2016 (FOCUS)]
 
−
|2010-2012
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Carfilzomib_monotherapy|Carfilzomib]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: cyclophosphamide was described as optional for the control arm but 95% of patients received it. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*At least 3 lines of therapy including bortezomib, lenalidomide or thalidomide, an alkylating agent, and corticosteroids
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 6 mg PO once every other day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''FOCUS:''' Hájek R, Masszi T, Petrucci MT, Palumbo A, Rosiñol L, Nagler A, Yong KL, Oriol A, Minarik J, Pour L, Dimopoulos MA, Maisnar V, Rossi D, Kasparu H, Van Droogenbroeck J, Yehuda DB, Hardan I, Jenner M, Calbecka M, Dávid M, de la Rubia J, Drach J, Gasztonyi Z, Górnik S, Leleu X, Munder M, Offidani M, Zojer N, Rajangam K, Chang YL, San-Miguel JF, Ludwig H. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Leukemia. 2017 Jan;31(1):107-114. Epub 2016 Jun 24. [https://doi.org/10.1038/leu.2016.176 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220126/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27416912 PubMed] NCT01302392
 
−
==Cyclophosphamide & Prednisone {{#subobject:969973|Regimen=1}}==
 
−
CP: '''<u>C</u>'''yclophosphamide & '''<u>P</u>'''rednisone
 
−
<br>CyPred: '''<u>Cy</u>'''clophosphamide & '''<u>Pred</u>'''nisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:bcd1ee|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220126/ Hájek et al. 2016 (FOCUS)]
 
−
|2010-2012
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Carfilzomib_monotherapy|Carfilzomib]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: cyclophosphamide was described as optional for the control arm but 95% of patients received it. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*At least 3 lines of therapy including bortezomib, lenalidomide or thalidomide, an alkylating agent, and corticosteroids
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 30 mg PO once every other day
 
−
'''Continued indefinitely'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:0a11f4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0300-2977(01)00140-1 de Weerdt et al. 2001]
 
−
|NR in abstract
 
−
|style="background-color:#91cf61"|Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg PO once per day
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 10 to 20 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# de Weerdt O, van de Donk NW, Veth G, Bloem AC, Hagenbeek A, Lokhorst HM. Continuous low-dose cyclophosphamide-prednisone is effective and well tolerated in patients with advanced multiple myeloma. Neth J Med. 2001 Aug;59(2):50-6. [https://doi.org/10.1016/s0300-2977(01)00140-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11476912 PubMed]
 
−
# '''FOCUS:''' Hájek R, Masszi T, Petrucci MT, Palumbo A, Rosiñol L, Nagler A, Yong KL, Oriol A, Minarik J, Pour L, Dimopoulos MA, Maisnar V, Rossi D, Kasparu H, Van Droogenbroeck J, Yehuda DB, Hardan I, Jenner M, Calbecka M, Dávid M, de la Rubia J, Drach J, Gasztonyi Z, Górnik S, Leleu X, Munder M, Offidani M, Zojer N, Rajangam K, Chang YL, San-Miguel JF, Ludwig H. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Leukemia. 2017 Jan;31(1):107-114. Epub 2016 Jun 24. [https://doi.org/10.1038/leu.2016.176 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220126/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27416912 PubMed] NCT01302392
 
−
==Ixazomib & Dexamethasone {{#subobject:af43a2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 4/20 {{#subobject:0ec76c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558585/ Kumar et al. 2015 (MC1181)]
 
−
|2013-2015
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-de-esc)
 
−
|[[#Ixazomib_.26_Dexamethasone|Ixazomib & Dexamethasone]]; 5.5/20
 
−
|style="background-color:#fee08b"|Might have inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*At least 1 prior line of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ixazomib (Ninlaro)]] 4 mg PO once per day on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 8, 9, 15, 16
 
−
====Supportive therapy====
 
−
*Herpes zoster prophylaxis
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 5.5/20 {{#subobject:55fb47|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558585/ Kumar et al. 2015 (MC1181)]
 
−
|2013-2015
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
 
−
|[[#Ixazomib_.26_Dexamethasone|Ixazomib & Dexamethasone]]; 4/20
 
−
|style="background-color:#d9ef8b"|Might have superior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*At least 1 prior line of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ixazomib (Ninlaro)]] 5.5 mg PO once per day on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 8, 9, 15, 16
 
−
====Supportive therapy====
 
−
*Herpes zoster prophylaxis
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MC1181:''' Kumar SK, LaPlant B, Roy V, Reeder CB, Lacy MQ, Gertz MA, Laumann K, Thompson MA, Witzig TE, Buadi FK, Rivera CE, Mikhael JR, Bergsagel PL, Kapoor P, Hwa L, Fonseca R, Stewart AK, Chanan-Khan A, Rajkumar SV, Dispenzieri A. Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib. Blood Cancer J. 2015 Aug 14;5:e338. [https://doi.org/10.1038/bcj.2015.60 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558585/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26275080 PubMed] NCT01415882
 
−
## '''Update:''' Kumar SK, LaPlant BR, Reeder CB, Roy V, Halvorson AE, Buadi F, Gertz MA, Bergsagel PL, Dispenzieri A, Thompson MA, Crawley J, Kapoor P, Mikhael J, Stewart K, Hayman SR, Hwa YL, Gonsalves W, Witzig TE, Ailawadhi S, Dingli D, Go RS, Lin Y, Rivera CE, Rajkumar SV, Lacy MQ. Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib. Blood. 2016 Nov 17;128(20):2415-2422. [https://doi.org/10.1182/blood-2016-05-717769 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114487/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27702799 PubMed]
 
−
==Lenalidomide & Dexamethasone (Rd) {{#subobject:d6803b|Regimen=1}}==
 
−
Rd: '''<u>R</u>'''evlimid (Lenalidomide) & low-dose '''<u>d</u>'''examethasone
 
−
<br>RevDex: '''<u>Rev</u>'''limid (Lenalidomide) & '''<u>Dex</u>'''amethasone
 
−
<br>Ld: '''<u>L</u>'''enalidomide & low-dose '''<u>d</u>'''examethasone
 
−
<br>LenDex: '''<u>L</u>'''enalidomide & '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, Len @ 25 mg 21/28 {{#subobject:107197|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1411321 Stewart et al. 2014 (ASPIRE)]
 
−
|2010-2012
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#KRd|KRd]]
 
−
|style="background-color:#d73027"|Inferior OS<sup>1</sup>
 
−
|style="background-color:#d73027"|Inferior GHS/QoL
 
−
|-
 
−
|[https://doi.org/10.1038/s41375-020-0948-0 Goldschmidt et al. 2020 (ReLApsE)]
 
−
|2010-2016
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]] x 3, then [[#Melphalan.2C_then_auto_HSCT|Melphalan auto HSCT]], then Lenalidomide
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1505654 Lonial et al. 2015 (ELOQUENT-2)]
 
−
|2011-2012
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Elo-Rd|Elo-Rd]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior OS<sup>2</sup>
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1516282 Moreau et al. 2016 (TOURMALINE-MM1)]
 
−
|2012-2014
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#IRd|IRd]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1607751 Dimopoulos et al. 2016 (POLLUX)]
 
−
|2014-2015
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Dara-Rd|Dara-Rd]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500972/ Hou et al. 2017 (TOURMALINE-MM1 China Continuation)]
 
−
|2014-2015
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#IRd|IRd]]
 
−
|style="background-color:#d73027"|Inferior OS
 
−
|
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for ASPIRE is based on the 2018 update.''<br>
 
−
''<sup>2</sup>Reported efficacy for ELOQUENT-2 is based on the 2020 update.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*ASPIRE, ReLApsE, ELOQUENT-2, TOURMALINE-MM1, POLLUX, TOURMALINE-MM1 China Continuation: 1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
**'''POLLUX:''' Patients with CrCl of 30 to 60 mL/min/1.73m<sup>2</sup> received 10 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
**'''POLLUX:''' Patients older than 75 years or underweight (BMI less than 18.5) could receive 20 mg
 
−
====Supportive therapy====
 
−
''Best described by ASPIRE:''
 
−
*[[Valacyclovir (Valtrex)]] (dose not specified) or equivalent [[:Category:Antivirals|antiviral]] while taking [[Lenalidomide (Revlimid)]]
 
−
*[[Aspirin]] (dose not specified) or other [[:Category:Anticoagulants|anticoagulant]] or [[:Category:Antiplatelet_agents|antiplatelet]] medication such as [[Clopidogrel (Plavix)]], [[:Category:Low_molecular_weight_heparins|low-molecular-weight heparin]] or [[Warfarin (Coumadin)]] while taking [[Lenalidomide (Revlimid)]]
 
−
*[[:Category:Bisphosphonates|Bisphosphonates]] while taking [[Dexamethasone (Decadron)]]
 
−
*[[Lansoprazole (Prevacid)]] (dose not specified) or other [[:Category:Proton_pump_inhibitors|proton pump inhibitor]] while taking [[Dexamethasone (Decadron)]]
 
−
*A prophylactic antibiotic ([[Ciprofloxacin (Cipro)]], [[Amoxicillin]], [[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] are given as examples)
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, Len @ 25 mg 21/28, with high-dose dex lead-in {{#subobject:60e23c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa070596 Weber et al. 2007 (MM-009)]
 
−
|2003-2004
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[Multiple_myeloma_-_historical#Dexamethasone_monotherapy_3|Dexamethasone]]
 
−
|style="background-color:#91cf60"|Seems to have superior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa070594 Dimopoulos et al. 2007 (MM-010)]
 
−
|2003-2004
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[Multiple_myeloma_-_historical#Dexamethasone_monotherapy_3|Dexamethasone]]
 
−
|style="background-color:#91cf60"|Seems to have superior OS<br>Median OS: NYR vs 20.6 mo<br>(HR 0.66, 95% CI 0.45-0.96)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy of MM-009 is based on the 2009 pooled update.''<br>
 
−
''Note: MM-009 is "Study 1" and MM-010 is "Study 2" listed in the package insert.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*MM-009 & MM-010: At least 1 prior line of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 4: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycle 5 onwards: 40 mg PO once per day on days 1 to 4
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, Len @ 30 mg 21/28 {{#subobject:94d1ca|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895441/ Richardson et al. 2006]
 
−
|2002-2003
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic)
 
−
|[[#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]]; twice-daily Lenalidomide
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: This regimen variant is essentially of historical interest.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*Relapse after prior chemotherapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Lenalidomide_monotherapy|Lenalidomide]] x 2
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 30 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 15 to 18
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
 
−
===Regimen variant #4, Len @ 15 mg 21/28 ("RevLite") {{#subobject:f184d5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.14562 Quach et al. 2017 (RevLite)]
 
−
|2007-NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 4: 20 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycle 5 onwards: 20 mg PO once per day on days 1 to 4
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M, Schlossman RL, Rajkumar SV, Desikan KR, Hideshima T, Munshi NC, Kelly-Colson K, Doss D, McKenney ML, Gorelik S, Warren D, Freeman A, Rich R, Wu A, Olesnyckyj M, Wride K, Dalton WS, Zeldis J, Knight R, Weller E, Anderson KC. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood. 2006 Nov 15;108(10):3458-64. Epub 2006 Jul 13. [http://www.bloodjournal.org/content/108/10/3458.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895441/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16840727 PubMed]
 
−
# '''MM-010:''' Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foà R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32. [https://doi.org/10.1056/NEJMoa070594 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18032762 PubMed] NCT00424047
 
−
## '''Pooled update:''' Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009 Nov;23(11):2147-52. Epub 2009 Jul 23. [https://doi.org/10.1038/leu.2009.147 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19626046 PubMed]
 
−
# '''MM-009:''' Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD; Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007 Nov 22;357(21):2133-42. [https://doi.org/10.1056/NEJMoa070596 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18032763 PubMed] NCT00056160
 
−
## '''Pooled update:''' Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009 Nov;23(11):2147-52. Epub 2009 Jul 23. [https://doi.org/10.1038/leu.2009.147 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19626046 PubMed]
 
−
# '''ASPIRE:''' Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, Hájek R, Rosiñol L, Siegel DS, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Wang M, Maisnar V, Minarik J, Bensinger WI, Mateos MV, Ben-Yehuda D, Kukreti V, Zojwalla N, Tonda ME, Yang X, Xing B, Moreau P, Palumbo A; ASPIRE Investigators. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015 Jan 8;372(2):142-52. Epub 2014 Dec 6. [https://doi.org/10.1056/NEJMoa1411321 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25482145 PubMed] NCT01080391
 
−
## '''Subgroup analysis:''' Avet-Loiseau H, Fonseca R, Siegel D, Dimopoulos MA, Špička I, Masszi T, Hájek R, Rosiñol L, Goranova-Marinova V, Mihaylov G, Maisnar V, Mateos MV, Wang M, Niesvizky R, Oriol A, Jakubowiak A, Minarik J, Palumbo A, Bensinger W, Kukreti V, Ben-Yehuda D, Stewart AK, Obreja M, Moreau P. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma. Blood. 2016 Sep 1;128(9):1174-80. Epub 2016 Jul 20. [http://www.bloodjournal.org/content/128/9/1174.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009511/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27439911 PubMed]
 
−
## '''HRQoL analysis:''' Stewart AK, Dimopoulos MA, Masszi T, Špička I, Oriol A, Hájek R, Rosiñol L, Siegel DS, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Buchanan J, Cocks K, Yang X, Xing B, Zojwalla N, Tonda M, Moreau P, Palumbo A. Health-related quality-of-life results from the open-label, randomized, phase III ASPIRE trial evaluating carfilzomib, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed multiple myeloma. J Clin Oncol. 2016 Nov 10;34(32):3921-3930. [https://doi.org/10.1200/JCO.2016.66.9648 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27601539 PubMed]
 
−
## '''Update:''' Siegel DS, Dimopoulos MA, Ludwig H, Facon T, Goldschmidt H, Jakubowiak A, San-Miguel J, Obreja M, Blaedel J, Stewart AK. Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol. 2018 Mar 10;36(8):728-734. Epub 2018 Jan 17. [https://doi.org/10.1200/JCO.2017.76.5032 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29341834 PubMed]
 
−
# '''ELOQUENT-2:''' Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, Walter-Croneck A, Moreau P, Mateos MV, Magen H, Belch A, Reece D, Beksac M, Spencer A, Oakervee H, Orlowski RZ, Taniwaki M, Röllig C, Einsele H, Wu KL, Singhal A, San-Miguel J, Matsumoto M, Katz J, Bleickardt E, Poulart V, Anderson KC, Richardson P; ELOQUENT-2 Investigators. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015 Aug 13;373(7):621-31. Epub 2015 Jun 2. [https://doi.org/10.1056/NEJMoa1505654 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26035255 PubMed] NCT01239797
 
−
## '''Update:''' Dimopoulos MA, Lonial S, White D, Moreau P, Palumbo A, San-Miguel J, Shpilberg O, Anderson K, Grosicki S, Spicka I, Walter-Croneck A, Magen H, Mateos MV, Belch A, Reece D, Beksac M, Bleickardt E, Poulart V, Sheng J, Sy O, Katz J, Singhal A, Richardson P. Elotuzumab plus lenalidomide/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT-2 follow-up and post-hoc analyses on progression-free survival and tumour growth. Br J Haematol. 2017 Sep;178(6):896-905. Epub 2017 Jul 5. [https://doi.org/10.1111/bjh.14787 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28677826 PubMed]
 
−
## '''Update:''' Dimopoulos MA, Lonial S, Betts KA, Chen C, Zichlin ML, Brun A, Signorovitch JE, Makenbaeva D, Mekan S, Sy O, Weisel K, Richardson PG. Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended 4-year follow-up and analysis of relative progression-free survival from the randomized ELOQUENT-2 trial. Cancer. 2018 Oct 15;124(20):4032-4043. Epub 2018 Sep 11. [https://doi.org/10.1002/cncr.31680 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30204239 PubMed]
 
−
## '''Update:''' Dimopoulos MA, Lonial S, White D, Moreau P, Weisel K, San-Miguel J, Shpilberg O, Grosicki S, Špička I, Walter-Croneck A, Magen H, Mateos MV, Belch A, Reece D, Beksac M, Spencer A, Oakervee H, Orlowski RZ, Taniwaki M, Röllig C, Einsele H, Matsumoto M, Wu KL, Anderson KC, Jou YM, Ganetsky A, Singhal AK, Richardson PG. Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study. Blood Cancer J. 2020 Sep 4;10(9):91. [https://doi.org/10.1038/s41408-020-00357-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474076/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32887873/ PubMed]
 
−
<!-- # '''Abstract:''' Philippe Moreau, MD, Tamás Masszi, MD, Norbert Grzasko, MD, PhD, Nizar J Bahlis, MD, Markus Hansson, Ludek Pour, MD, Irwindeep Sandhu, MD, Peter Ganly, BMBCh, PhD, Bartrum W Baker, MBChB, FRACP, FRCPA, Sharon Jackson, MBChB, FRACP, FRCPA, Anne-Marie Stoppa, MD, David R Simpson, MBChB, FRACP, FRCPA, Peter Gimsing, MD, DMSci, Antonio Palumbo, Laurent Garderet, MD, Michele Cavo, Shaji K. Kumar, MD, Cyrille Touzeau, MD, Francis Buadi, MD, Jacob P. Laubach, MD, Jianchang Lin, PhD, Deborah Berg, RN, MSN, Alessandra DiBacco, PhD, Ai-Min Hui, MD, PhD and Paul G. Richardson, MD. Ixazomib, an Investigational Oral Proteasome Inhibitor (PI), in Combination with Lenalidomide and Dexamethasone (IRd), Significantly Extends Progression-Free Survival (PFS) for Patients (Pts) with Relapsed and/or Refractory Multiple Myeloma (RRMM): The Phase 3 Tourmaline-MM1 Study (NCT01564537). ASH Annual Meeting 2015 Abstract 727 [https://ash.confex.com/ash/2015/webprogram/Paper79829.html link to abstract] -->
 
−
# '''TOURMALINE-MM1:''' Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Simpson DR, Gimsing P, Palumbo A, Garderet L, Cavo M, Kumar S, Touzeau C, Buadi FK, Laubach JP, Berg DT, Lin J, Di Bacco A, Hui AM, van de Velde H, Richardson PG; TOURMALINE-MM1 Study Group. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016 Apr 28;374(17):1621-1634. [https://doi.org/10.1056/NEJMoa1516282 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27119237 PubMed] NCT01564537
 
−
## '''Subgroup analysis:''' Avet-Loiseau H, Bahlis NJ, Chng WJ, Masszi T, Viterbo L, Pour L, Ganly P, Palumbo A, Cavo M, Langer C, Pluta A, Nagler A, Kumar S, Ben-Yehuda D, Rajkumar SV, San-Miguel J, Berg D, Lin J, van de Velde H, Esseltine DL, di Bacco A, Moreau P, Richardson PG. Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. Blood. 2017 Dec 14;130(24):2610-2618. Epub 2017 Oct 20. [http://www.bloodjournal.org/content/130/24/2610.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/29054911 PubMed]
 
−
## '''Update:''' Richardson PG, Kumar SK, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Gimsing P, Garderet L, Touzeau C, Buadi FK, Laubach JP, Cavo M, Darif M, Labotka R, Berg D, Moreau P. Final Overall Survival Analysis of the TOURMALINE-MM1 Phase III Trial of Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma. J Clin Oncol. 2021 Aug 1;39(22):2430-2442. Epub 2021 Jun 11. [https://doi.org/10.1200/jco.21.00972 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34111952/ PubMed]
 
−
# '''POLLUX:''' Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P; POLLUX Investigators. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016 Oct 6;375(14):1319-1331. [https://doi.org/10.1056/NEJMoa1607751 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1607751/suppl_file/nejmoa1607751_protocol.pdf link to original protocol] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27705267 PubMed] NCT02076009
 
−
## '''Update:''' Dimopoulos MA, San-Miguel J, Belch A, White D, Benboubker L, Cook G, Leiba M, Morton J, Ho PJ, Kim K, Takezako N, Moreau P, Kaufman JL, Sutherland HJ, Lalancette M, Magen H, Iida S, Kim JS, Prince HM, Cochrane T, Oriol A, Bahlis NJ, Chari A, O' Rourke L, Wu K, Schecter JM, Casneuf T, Chiu C, Soong D, Sasser AK, Khokhar NZ, Avet-Loiseau H, Usmani SZ. Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Haematologica. 2018 Dec;103(12):2088-96. Epub 2018 Sep 20. [https://doi.org/10.3324/haematol.2018.194282 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6269302/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30237262 PubMed]
 
−
## '''Update:''' Bahlis NJ, Dimopoulos MA, White DJ, Benboubker L, Cook G, Leiba M, Ho PJ, Kim K, Takezako N, Moreau P, Kaufman JL, Krevvata M, Chiu C, Qin X, Okonkwo L, Trivedi S, Ukropec J, Qi M, San-Miguel J. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia. 2020 Jul;34(7):1875-1884. Epub 2020 Jan 30. [https://doi.org/10.1038/s41375-020-0711-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7326710/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32001798 PubMed]
 
−
# '''RevLite:''' Quach H, Fernyhough L, Henderson R, Corbett G, Baker B, Browett P, Blacklock H, Forsyth C, Underhill C, Cannell P, Trotman J, Neylon A, Harrison S, Link E, Swern A, Cowan L, Dimopoulos MA, Miles Prince H. Upfront lower dose lenalidomide is less toxic and does not compromise efficacy for vulnerable patients with relapsed refractory multiple myeloma: final analysis of the phase II RevLite study. Br J Haematol. 2017 May;177(3):441-448. Epub 2017 Feb 15. [https://doi.org/10.1111/bjh.14562 link to original article]'''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28197996 PubMed] NCT00482261
 
−
# '''TOURMALINE-MM1 China Continuation:''' Hou J, Jin J, Xu Y, Wu D, Ke X, Zhou D, Lu J, Du X, Chen X, Li J, Liu J, Gupta N, Hanley MJ, Li H, Hua Z, Wang B, Zhang X, Wang H, van de Velde H, Richardson PG, Moreau P. Randomized, double-blind, placebo-controlled phase III study of ixazomib plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma: China Continuation study. J Hematol Oncol. 2017 Jul 6;10(1):137. [https://doi.org/10.1186/s13045-017-0501-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500972/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28683766 PubMed] NCT01564537
 
−
# '''ReLApsE:''' Goldschmidt H, Baertsch MA, Schlenzka J, Becker N, Habermehl C, Hielscher T, Raab MS, Hillengass J, Sauer S, Müller-Tidow C, Luntz S, Jauch A, Hose D, Seckinger A, Brossart P, Goerner M, Klein S, Schmidt-Hieber M, Reimer P, Graeven U, Fenk R, Haenel M, Martin H, Lindemann HW, Scheid C, Nogai A, Salwender H, Noppeney R, Besemer B, Weisel K; German Myeloma Multicenter Group (GMMG). Salvage autologous transplant and lenalidomide maintenance vs lenalidomide/dexamethasone for relapsed multiple myeloma: the randomized GMMG phase III trial ReLApsE. Leukemia. 2021 Apr;35(4):1134-1144. Epub 2020 Jul 21. [https://doi.org/10.1038/s41375-020-0948-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32694619/ PubMed] ISRCTN16345835
 
−
==Pomalidomide & Dexamethasone (Pd) {{#subobject:06b435|Regimen=1}}==
 
−
Pd: '''<u>P</u>'''omalidomide & low-dose '''<u>d</u>'''examethasone
 
−
<br>PomDex: '''<u>Pom</u>'''alidomide & '''<u>Dex</u>'''amethasone
 
−
<br>Pom + LoDEX: '''<u>Pom</u>'''alidomide & '''<u>Lo</u>'''w-dose '''<u>Dex</u>'''amethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 4 mg 21/28 {{#subobject:ed2ee6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/121/11/1968.long Leleu et al. 2013 (IFM 2009-02)]
 
−
|2009-2010
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-de-esc)
 
−
|[[#Pomalidomide_.26_Dexamethasone_.28Pd.29|Pd]]; 28/28
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962162/ Richardson et al. 2014 (CC-4047-MM-002)]
 
−
|2009-NR
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-RT-esc)
 
−
|[[#Pomalidomide_monotherapy|Pomalidomide]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 4.2 vs 2.7 mo<br>(HR 0.68, 95% CI 0.51-0.90)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(13)70380-2 San Miguel et al. 2013 (NIMBUS)]
 
−
|2011-2012
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[Multiple_myeloma_-_historical#Dexamethasone_monotherapy_3|Dexamethasone]]
 
−
|style="background-color:#1a9850"|Superior OS<sup>1</sup><br>Median OS: 13.1 vs 8.1 mo<br>(HR 0.72)
 
−
|-
 
−
|[http://www.bloodjournal.org/content/127/21/2561.long Baz et al. 2016 (PO-MM-PI-0039)]
 
−
|2011-2014
 
−
|style="background-color:#1a9851"|Randomized Phase 1/2 (C)
 
−
|[[#PCD|PomCyDex]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior ORR rate
 
−
|-
 
−
|[http://www.bloodjournal.org/content/125/9/1411.long Leleu et al. 2015 (IFM 2010-02)]
 
−
|2012-2013
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009959/ Dimopoulos et al. 2016 (STRATUS)]
 
−
|2012-2014
 
−
|style="background-color:#91cf61"|Phase 3b
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://doi.org/10.1016/S2352-3026(19)30110-3 Mateos et al. 2019 (KEYNOTE-183)]
 
−
|2016-2017
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Stub#PD_.26_Pembrolizumab|PD & Pembrolizumab]]
 
−
| style="background-color:#1a9850" |Superior PFS<sup>2</sup><br>Median PFS: 8.4 vs 5.6 mo<br>(HR 0.65, 95% CI 0.45-0.95)
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(19)32556-5 Attal et al. 2019 (ICARIA-MM)]
 
−
|2017-2018
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Isa-Pd|Isa-Pd]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00128-5 Dimopoulos et al. 2021 (APOLLO)]
 
−
|2017-2019
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[#Dara-Pd|Dara-Pd]]<br> 2. [[#Dara-Pd_.28SC_daratumumab.29|Dara-Pd (SC daratumumab)]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1016/s2352-3026(21)00381-1 Schjesvold et al. 2022 (OCEAN)]
 
−
|2017-2020
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma_-_historical#Melphalan_flufenamide_.26_Dexamethasone|Melflufen flufenamide & Dexamethasone]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>efficacy reported for NIMBUS is based on the 2015 update.''<br>
 
−
''<sup>2</sup>KEYNOTE-183 was not designed to evaluate superiority in the control arm; nevertheless, an unplanned interim analysis found that the control arm had superior PFS.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*IFM 2009-02: At least 1 prior line of therapy
 
−
*CC-4047-MM-002 & NIMBUS: At least 2 prior lines of therapy including lenalidomide and bortezomib
 
−
*PO-MM-PI-0039: At least 2 prior lines of therapy including an immunomodulator; patients were required to be lenalidomide-refractory
 
−
*KEYNOTE-183: At least 2 prior lines of therapy not including pomalidomide
 
−
*ICARIA-MM: At least 2 prior lines of therapy including lenalidomide and a proteasome inhibitor
 
−
*APOLLO: At least 1 prior line of therapy including lenalidomide and a proteasome inhibitor
 
−
*OCEAN: 2 to 4 prior lines of therapy including lenalidomide and a proteasome inhibitor
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] by the following age-based criteria:
 
−
**75 or younger: 40 mg PO once per day on days 1, 8, 15, 22
 
−
**Older than 75: 20 mg PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*NIMBUS: Thromboprohpylaxis required. "Choice of thromboprophylaxis and use of myeloid and erythroid growth factors was left to the physician's discretion."
 
−
*IFM 2009-02: Thromboprophylaxis "at the physician's discretion"
 
−
*CC-4047-MM-002: [[Aspirin]] 81 to 100 mg PO once per day unless contraindicated
 
−
*PO-MM-PI-0039: [[Aspirin]] 81 mg PO once per day unless contraindicated
 
−
*STRATUS: Thromboprophylaxis with low-dose [[Aspirin]], [[:Category:Low_molecular_weight_heparins||LMWH]], or equivalent was required
 
−
*IFM 2009-02: [[Filgrastim (Neupogen) | G-CSF]] allowed beginning with cycle 2 and on
 
−
*ICARIA-MM: mandatory [[Aspirin]] or [[:Category:Low_molecular_weight_heparins||LMWH]]
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 4 mg continuous {{#subobject:306c08|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291492/ Lacy et al. 2011 (MC0789-2)]
 
−
|2009
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[http://www.bloodjournal.org/content/121/11/1968.long Leleu et al. 2013 (IFM 2009-02)]
 
−
|2009-2010
 
−
|style="background-color:#1a9851"|Randomized Phase 2, >20 patients (E-esc)
 
−
|[[#Pomalidomide_.26_Dexamethasone_.28Pd.29|Pd]]; 21/28
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: Lacy et al. 2011 is registered under MC0789 but is described as a sequential phase 2 trial, distinct from Lacy et al. 2009.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*IFM 2009-02: At least 1 prior line of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 28
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*MC0789-2: [[Aspirin]] 325 mg PO once per day
 
−
**[[:Category:Low_molecular_weight_heparins|low molecular weight heparin]] or [[Warfarin (Coumadin)]] could be substituted at physician discretion
 
−
*IFM 2009-02: Thromboprophylaxis "at the physician's discretion"
 
−
*IFM 2009-02: [[Filgrastim (Neupogen) | G-CSF]] allowed beginning with cycle 2 and on
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 2 mg continuous {{#subobject:567775|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2009.23.6802 Lacy et al. 2009 (MC0789)]
 
−
|2007-2008
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]] 2 mg PO once per day on days 1 to 28
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 325 mg PO once per day
 
−
**[[:Category:Low_molecular_weight_heparins|Low molecular weight heparin]] or [[Warfarin (Coumadin)]] could be substituted at physician discretion
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MC0789:''' Lacy MQ, Hayman SR, Gertz MA, Dispenzieri A, Buadi F, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Kyle RA, Fonseca R, Bergsagel PL, Roy V, Mikhael JR, Stewart AK, Laumann K, Allred JB, Mandrekar SJ, Rajkumar SV. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol. 2009 Oct 20;27(30):5008-14. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.23.6802 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19720894 PubMed] NCT00558896
 
−
## '''Update:''' Lacy MQ, Hayman SR, Gertz MA, Short KD, Dispenzieri A, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Zeldenrust S, Fonseca R, Bergsagel PL, Roy V, Mikhael JR, Stewart AK, Laumann K, Allred JB, Mandrekar SJ, Rajkumar SV, Buadi F. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia. 2010 Nov;24(11):1934-9. Epub 2010 Sep 9. [https://doi.org/10.1038/leu.2010.190 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978257/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20827286 PubMed]
 
−
## '''Update:''' Lacy MQ, Allred JB, Gertz MA, Hayman SR, Short KD, Buadi F, Dispenzieri A, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Zeldenrust S, Fonseca R, Bergsagel PL, Roy V, Stewart AK, Laumann K, Mandrekar SJ, Reeder C, Rajkumar SV, Mikhael JR. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood. 2011 Sep 15;118(11):2970-5. Epub 2011 Jun 20. [http://www.bloodjournal.org/content/118/11/2970.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291492/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21690557 PubMed]
 
−
# '''IFM 2009-02:''' Leleu X, Attal M, Arnulf B, Moreau P, Traulle C, Marit G, Mathiot C, Petillon MO, Macro M, Roussel M, Pegourie B, Kolb B, Stoppa AM, Hennache B, Bréchignac S, Meuleman N, Thielemans B, Garderet L, Royer B, Hulin C, Benboubker L, Decaux O, Escoffre-Barbe M, Michallet M, Caillot D, Fermand JP, Avet-Loiseau H, Facon T. Pomalidomide plus low dose dexamethasone is active and well tolerated in bortezomib and lenalidomide refractory multiple myeloma: IFM 2009-02. Blood. 2013 Mar 14;121(11):1968-1975. Epub 2013 Jan 14. [http://www.bloodjournal.org/content/121/11/1968.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23319574 PubMed] NCT01053949
 
−
# '''NIMBUS:''' San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-66. Epub 2013 Sep 3. [https://doi.org/10.1016/S1470-2045(13)70380-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24007748 PubMed] NCT01311687
 
−
## '''Update:''' Dimopoulos MA, Weisel KC, Song KW, Delforge M, Karlin L, Goldschmidt H, Moreau P, Banos A, Oriol A, Garderet L, Cavo M, Ivanova V, Alegre A, Martinez-Lopez J, Chen C, Spencer A, Knop S, Bahlis NJ, Renner C, Yu X, Hong K, Sternas L, Jacques C, Zaki MH, San Miguel JF. Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone. Haematologica. 2015 Oct;100(10):1327-33. Epub 2015 Aug 6. [http://www.haematologica.org/content/100/10/1327.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591765/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26250580 PubMed]
 
−
# '''CC-4047-MM-002:''' Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, Chen C, Lonial S, Jakubowiak A, Bahlis N, Song K, Belch A, Raje N, Shustik C, Lentzsch S, Lacy M, Mikhael J, Matous J, Vesole D, Chen M, Zaki MH, Jacques C, Yu Z, Anderson K. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014 Mar 20;123(12):1826-32. Epub 2014 Jan 13. Erratum in: Blood. 2014 May 15;123(20):3208-9. [http://www.bloodjournal.org/content/123/12/1826.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962162/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24421329 PubMed] NCT00833833
 
−
# '''IFM 2010-02:''' Leleu X, Karlin L, Macro M, Hulin C, Garderet L, Roussel M, Arnulf B, Pegourie B, Kolb B, Stoppa AM, Brechiniac S, Marit G, Thielemans B, Onraed B, Mathiot C, Banos A, Lacotte L, Tiab M, Dib M, Fuzibet JG, Petillon MO, Rodon P, Wetterwald M, Royer B, Legros L, Benboubker L, Decaux O, Escoffre-Barbe M, Caillot D, Fermand JP, Moreau P, Attal M, Avet-Loiseau H, Facon T; Intergroupe Francophone du Myélome. Pomalidomide plus low-dose dexamethasone in multiple myeloma with deletion 17p and/or translocation (4;14): IFM 2010-02 trial results. Blood. 2015 Feb 26;125(9):1411-7. Epub 2015 Jan 9. [http://www.bloodjournal.org/content/125/9/1411.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25575538 PubMed] NCT01745640
 
−
<!-- Presented in part at the annual meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
 
−
# '''PO-MM-PI-0039:''' Baz RC, Martin TG 3rd, Lin HY, Zhao X, Shain KH, Cho HJ, Wolf JL, Mahindra A, Chari A, Sullivan DM, Nardelli LA, Lau K, Alsina M, Jagannath S. Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 2016 May 26;127(21):2561-8. Epub 2016 Mar 1. Erratum in: Blood. 2016 Jul 21;128(3):461. [http://www.bloodjournal.org/content/127/21/2561.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26932802 PubMed] NCT01432600
 
−
# '''STRATUS:''' Dimopoulos MA, Palumbo A, Corradini P, Cavo M, Delforge M, Di Raimondo F, Weisel KC, Oriol A, Hansson M, Vacca A, Blanchard MJ, Goldschmidt H, Doyen C, Kaiser M, Petrini M, Anttila P, Cafro AM, Raymakers R, San-Miguel J, de Arriba F, Knop S, Röllig C, Ocio EM, Morgan G, Miller N, Simcock M, Peluso T, Herring J, Sternas L, Zaki MH, Moreau P. Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma. Blood. 2016 Jul 28;128(4):497-503. Epub 2016 May 25. [http://www.bloodjournal.org/content/128/4/497.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009959/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27226434 PubMed] NCT01712789
 
−
# '''ELOQUENT-3:''' Dimopoulos MA, Dytfeld D, Grosicki S, Moreau P, Takezako N, Hori M, Leleu X, LeBlanc R, Suzuki K, Raab MS, Richardson PG, Popa McKiver M, Jou YM, Shelat SG, Robbins M, Rafferty B, San-Miguel J. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018 Nov 8;379(19):1811-1822. [https://doi.org/10.1056/NEJMoa1805762 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30403938 PubMed] NCT02654132
 
−
# '''KEYNOTE-183:''' Mateos MV, Blacklock H, Schjesvold F, Oriol A, Simpson D, George A, Goldschmidt H, Larocca A, Chanan-Khan A, Sherbenou D, Avivi I, Benyamini N, Iida S, Matsumoto M, Suzuki K, Ribrag V, Usmani SZ, Jagannath S, Ocio EM, Rodriguez-Otero P, San Miguel J, Kher U, Farooqui M, Liao J, Marinello P, Lonial S; KEYNOTE-183 Investigators. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial. Lancet Haematol. 2019 Jul 18. [Epub ahead of print] [https://doi.org/10.1016/S2352-3026(19)30110-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31327687 PubMed] NCT02576977
 
−
# '''ICARIA-MM:''' Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Macé S, Corzo KP, Campana F, Le-Guennec S, Dubin F, Anderson KC; ICARIA-MM study group. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019 Dec 7;394(10214):2096-2107. Epub 2019 Nov 14. Erratum in: Lancet. 2019 Dec 7;394(10214):2072. [https://doi.org/10.1016/s0140-6736(19)32556-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31735560 PubMed] NCT02990338
 
−
##'''Update:''' Richardson PG, Perrot A, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Malinge L, Dubin F, van de Velde H, Anderson KC. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study. Lancet Oncol. 2022 Mar;23(3):416-427. Epub 2022 Feb 10. [https://doi.org/10.1016/s1470-2045(22)00019-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35151415/ PubMed]
 
−
# '''APOLLO:''' Dimopoulos MA, Terpos E, Boccadoro M, Delimpasi S, Beksac M, Katodritou E, Moreau P, Baldini L, Symeonidis A, Bila J, Oriol A, Mateos MV, Einsele H, Orfanidis I, Ahmadi T, Ukropec J, Kampfenkel T, Schecter JM, Qiu Y, Amin H, Vermeulen J, Carson R, Sonneveld P; APOLLO Trial Investigators. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Jun;22(6):801-812. [https://doi.org/10.1016/s1470-2045(21)00128-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34087126/ PubMed] NCT03180736
 
−
# '''OCEAN:''' Schjesvold FH, Dimopoulos MA, Delimpasi S, Robak P, Coriu D, Legiec W, Pour L, Špička I, Masszi T, Doronin V, Minarik J, Salogub G, Alekseeva Y, Lazzaro A, Maisnar V, Mikala G, Rosiñol L, Liberati AM, Symeonidis A, Moody V, Thuresson M, Byrne C, Harmenberg J, Bakker NA, Hájek R, Mateos MV, Richardson PG, Sonneveld P; OCEAN (OP-103) Investigators. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study. Lancet Haematol. 2022 Feb;9(2):e98-e110. Epub 2022 Jan 12. [https://doi.org/10.1016/s2352-3026(21)00381-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35032434/ PubMed] NCT03151811
 
−
# '''CANOVA:''' NCT03539744
 
−
# '''CheckMate 602:''' NCT02726581
 
−
==Selinexor & Dexamethasone (Sd) {{#subobject:gg99e1|Regimen=1}}==
 
−
Sd: '''<u>S</u>'''elinexor & low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:48b2e3|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6905485/ Vogl et al. 2018 (STORM)]
 
−
|2015-2018
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Selinexor (Xpovio)]] 80 mg PO once per day on days 1, 3, 8, 10, 15, 17, 22, 24
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 3, 8, 10, 15, 17, 22, 24
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''STORM:''' Vogl DT, Dingli D, Cornell RF, Huff CA, Jagannath S, Bhutani D, Zonder J, Baz R, Nooka A, Richter J, Cole C, Vij R, Jakubowiak A, Abonour R, Schiller G, Parker TL, Costa LJ, Kaminetzky D, Hoffman JE, Yee AJ, Chari A, Siegel D, Fonseca R, Van Wier S, Ahmann G, Lopez I, Kauffman M, Shacham S, Saint-Martin JR, Picklesimer CD, Choe-Juliak C, Stewart AK. Selective inhibition of nuclear export with oral selinexor for treatment of relapsed or refractory multiple myeloma. J Clin Oncol. 2018 Mar 20;36(9):859-866. Epub 2018 Jan 30. [https://doi.org/10.1200/JCO.2017.75.5207 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6905485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29381435 PubMed] NCT02336815
 
−
## '''Update:''' Chari A, Vogl DT, Gavriatopoulou M, Nooka AK, Yee AJ, Huff CA, Moreau P, Dingli D, Cole C, Lonial S, Dimopoulos M, Stewart AK, Richter J, Vij R, Tuchman S, Raab MS, Weisel KC, Delforge M, Cornell RF, Kaminetzky D, Hoffman JE, Costa LJ, Parker TL, Levy M, Schreder M, Meuleman N, Frenzel L, Mohty M, Choquet S, Schiller G, Comenzo RL, Engelhardt M, Illmer T, Vlummens P, Doyen C, Facon T, Karlin L, Perrot A, Podar K, Kauffman MG, Shacham S, Li L, Tang S, Picklesimer C, Saint-Martin JR, Crochiere M, Chang H, Parekh S, Landesman Y, Shah J, Richardson PG, Jagannath S. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019 Aug 22;381(8):727-738. [https://doi.org/10.1056/NEJMoa1903455 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31433920 PubMed]
 
−
==Thalidomide & Dexamethasone (TD) {{#subobject:13f920|Regimen=1}}==
 
−
TD: '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone
 
−
<br>Thal-Dex: '''<u>Thal</u>'''idomide, '''<u>Dex</u>'''amethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, thalidomide 200, with lead-in {{#subobject:518b17|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492844/ Hjorth et al. 2012 (NMSG 17/07)]
 
−
|2007-2010
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Bort-Dex]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: this is an experimental arm that did not meet its primary endpoint, likely due to premature close of the study; included here because it was eventually used to establish this regimen as a standard comparator.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*NMSG 17/07: Failure of melphalan with no prior exposure to bortezomib or thalidomide
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day, increased by 50 mg every 3 weeks to a maximum of 200 mg PO once per day
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*"Antithrombotic prophylaxis and acyclovir prophylaxis were not mandatory according to the study protocol but used routinely in an increasing proportion of participating centers during the study period."
 
−
'''21-day cycles until progression or best response, which would then be followed by 1 to 2 additional cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, thalidomide 200 {{#subobject:c91582|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2011.37.4918 Garderet et al. 2012 (MMVAR/IFM 2005-04)]
 
−
|2006-2010
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#VTD|VTD]]
 
−
|style="background-color:#d73027"|Inferior TTP
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*At least 1 autologous stem-cell transplant
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Thalidomide (Thalomid)]] 200 mg PO once per day
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*[[Enoxaparin (Lovenox)]] 40 mg SC once per day for primary prophylaxis
 
−
*[[Warfarin (Coumadin)]] for secondary prophylaxis
 
−
'''21-day cycle for 18 cycles (1 year)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, thalidomide 400, with lead-in {{#subobject:4ea478|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1023/a:1011132808904 Dimopoulos et al. 2001]
 
−
|1999-2000
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Thalidomide (Thalomid)]] as follows:
 
−
**Cycle 1: 200 mg PO once per day for 14 days, then 400 mg PO once per day
 
−
**Cycle 2 onwards: 400 mg PO once per day
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycle 1: 20 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycle 2 onwards: 20 mg PO once per day on days 1 to 4
 
−
'''1-month cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Dimopoulos MA, Zervas K, Kouvatseas G, Galani E, Grigoraki V, Kiamouris C, Vervessou E, Samantas E, Papadimitriou C, Economou O, Gika D, Panayiotidis P, Christakis I, Anagnostopoulos N. Thalidomide and dexamethasone combination for refractory multiple myeloma. Ann Oncol. 2001 Jul;12(7):991-5. [https://doi.org/10.1023/a:1011132808904 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11521808 PubMed]
 
−
# '''NMSG 17/07:''' Hjorth M, Hjertner Ø, Knudsen LM, Gulbrandsen N, Holmberg E, Pedersen PT, Andersen NF, Andréasson B, Billström R, Carlson K, Carlsson MS, Flogegård M, Forsberg K, Gimsing P, Karlsson T, Linder O, Nahi H, Othzén A, Swedin A; Nordic Myeloma Study Group. Thalidomide and dexamethasone vs bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study. Eur J Haematol. 2012 Jun;88(6):485-96. Epub 2012 Mar 30. [https://doi.org/10.1111/j.1600-0609.2012.01775.x link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492844/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22404182 PubMed] NCT00602511
 
−
<!-- Presented at the 37th Annual Meeting of the European Group for Blood and Marrow Transplantation, Paris, France, April, 3-6, 2011. -->
 
−
# '''MMVAR/IFM 2005-04:''' Garderet L, Iacobelli S, Moreau P, Dib M, Lafon I, Niederwieser D, Masszi T, Fontan J, Michallet M, Gratwohl A, Milone G, Doyen C, Pegourie B, Hajek R, Casassus P, Kolb B, Chaleteix C, Hertenstein B, Onida F, Ludwig H, Ketterer N, Koenecke C, van Os M, Mohty M, Cakana A, Gorin NC, de Witte T, Harousseau JL, Morris C, Gahrton G. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 randomized phase III trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2012 Jul 10;30(20):2475-82. Epub 2012 May 14. Erratum in: J Clin Oncol. 2012 Sep 20;30(27):3429. [https://doi.org/10.1200/jco.2011.37.4918 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22585692 PubMed] NCT00256776
 
−
=Relapsed or refractory, triplets=
 
−
==BBD {{#subobject:adb507|Regimen=1}}==
 
−
BBD: '''<u>B</u>'''endamustine, '''<u>B</u>'''ortezomib, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:cc2b7d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924931/ Ludwig et al. 2013 (AFAC BBD)]
 
−
|2010-2012
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 70 mg/m<sup>2</sup> IV once per day on days 1 & 4
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg (route not specified) once per day on days 1, 4, 8, 11
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
'''28-day cycle for up to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''AFAC BBD:''' Ludwig H, Kasparu H, Leitgeb C, Rauch E, Linkesch W, Zojer N, Greil R, Seebacher A, Pour L, Weißmann A, Adam Z. Bendamustine-bortezomib-dexamethasone is an active and well tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood. 2014 Feb 13;123(7):985-91. Epub 2013 Nov 13. [http://www.bloodjournal.org/content/123/7/985.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924931/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24227817 PubMed] EudraCT 2008-006421-13
 
−
==BID {{#subobject:e877g5|Regimen=1}}==
 
−
BID: '''<u>B</u>'''endamustine, '''<u>I</u>'''xazomib, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:edc6yy|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663939/ Dhakal et al. 2019 (PRO00024991)]
 
−
|2015-2018
 
−
|style="background-color:#ffffbe"|Phase 1/2, <20 pts in MTD cohort
 
−
|-
 
−
|}
 
−
''Note: Dosages listed are the determined maximally tolerated doses (MTD) of this phase 1/2 trial. Note that dexamethasone is not given in week 4; this has been confirmed with the authors.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 80 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] by the following age-based criteria:
 
−
**Up to 75 years: 40 mg PO once per day on days 1, 8, 15
 
−
**Older than 75: 20 mg PO once per day on days 1, 8, 15
 
−
====Targeted therapy====
 
−
*[[Ixazomib (Ninlaro)]] 4 mg PO once per day on days 1, 8, 15
 
−
'''28-day cycle for up to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''PRO00024991:''' Dhakal B, D'Souza A, Hamadani M, Arce-Lara C, Schroeder K, Chhabra S, Shah NN, Gauger K, Keaton T, Pasquini M, Hari P. Phase I/II trial of bendamustine, ixazomib, and dexamethasone in relapsed/refractory multiple myeloma. Blood Cancer J. 2019 Jul 29;9(8):56. [https://www.nature.com/articles/s41408-019-0219-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663939/ link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31358733 PubMed] NCT02477215
 
−
 
−
==BLD {{#subobject:e8445|Regimen=1}}==
 
−
BLD: '''<u>B</u>'''endamustine, '''<u>L</u>'''enalidomide, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:edc866|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392072/ Lentzsch et al. 2012 (UPMC 07-089)]
 
−
|2008-2011
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|-
 
−
|}
 
−
''Note: Dosages listed are the determined maximally tolerated doses (MTD) of this phase 1/2 trial.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 75 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg (no route specified) once per day on days 1, 8, 15, 22
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 325 mg PO once per day
 
−
*"Gastroprotectant" ([[:Category:H2-receptor antagonists|H2-blocker]] or [[:Category:Proton pump inhibitors|PPI]])
 
−
'''28-day cycle for up to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Preliminary results were presented at the 53rd Annual Meeting of the American Society of Hematology, December 12, 2011, Orlando, FL. -->
 
−
# '''UPMC 07-089:''' Lentzsch S, O'Sullivan A, Kennedy RC, Abbas M, Dai L, Pregja SL, Burt S, Boyiadzis M, Roodman GD, Mapara MY, Agha M, Waas J, Shuai Y, Normolle D, Zonder JA. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood. 2012 May 17;119(20):4608-13. Epub 2012 Mar 26. [http://www.bloodjournal.org/content/119/20/4608.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392072/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22451423 PubMed] NCT01042704
 
−
 
−
==Bortezomib & Dexamethasone (Vd) & Panobinostat {{#subobject:PYR1|Regimen=1}}==
 
−
Vd & Panobinostat: '''<u>V</u>'''elcade (Bortezomib), low-dose '''<u>d</u>'''examethasone, Panobinostat
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:PYV1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/122/14/2331.full Richardson et al. 2013 (PANORAMA 2)]
 
−
|2010-2011
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70440-1 San-Miguel et al. 2014 (PANORAMA 1)]
 
−
|2010-2012
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Vd]]
 
−
|style="background-color:#1a9850"|Superior PFS<br>Median PFS: 12 vs 8.1 mo<br>(HR 0.63, 95% CI 0.52-0.76)
 
−
|-
 
−
|}
 
−
''Patients who had clinical benefit per the modified European Group for Blood and Marrow Transplantation [EBMT] criteria on day 1 of cycle 8 proceeded to cycle 9:''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*PANORAMA 1: 1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] as follows:
 
−
**Cycles 1 to 8: 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
**Cycles 9 to 16: 1.3 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Panobinostat (Farydak)]] 20 mg PO once per day on days 1, 3, 5, 8, 10, 12
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 8: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
**Cycles 9 to 16: 20 mg PO once per day on days 1, 2, 8, 9
 
−
'''21-day cycle for 16 cycles (PANORAMA 1) or indefinitely (PANORAMA 2)'''
 
−
</div></div>
 
−
===References===
 
−
# '''PANORAMA 2:''' Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C, Mukhopadhyay S, Ondovik MS, Khan M, Paley CS, Lonial S. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013 Oct 3;122(14):2331-7. [http://www.bloodjournal.org/content/122/14/2331.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23950178 PubMed] NCT01083602
 
−
<!-- Presented in abstract form at the American Society of Hematology Annual Meeting, Atlanta, GA, December 8-11, 2012. -->
 
−
# '''PANORAMA 1:''' San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Günther A, Nakorn TN, Siritanaratkul N, Corradini P, Chuncharunee S, Lee JJ, Schlossman RL, Shelekhova T, Yong K, Tan D, Numbenjapon T, Cavenagh JD, Hou J, LeBlanc R, Nahi H, Qiu L, Salwender H, Pulini S, Moreau P, Warzocha K, White D, Bladé J, Chen W, de la Rubia J, Gimsing P, Lonial S, Kaufman JL, Ocio EM, Veskovski L, Sohn SK, Wang MC, Lee JH, Einsele H, Sopala M, Corrado C, Bengoudifa BR, Binlich F, Richardson PG. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1195-206. Epub 2014 Sep 18. Erratum in: Lancet Oncol. 2015 Jan;16(1):e6. [https://doi.org/10.1016/S1470-2045(14)70440-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25242045 PubMed] NCT01023308
 
−
## '''Subgroup analysis:''' Richardson PG, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Guenther A, Nakorn TN, Siritanaratkul N, Schlossman RL, Hou J, Moreau P, Lonial S, Lee JH, Einsele H, Sopala M, Bengoudifa BR, Corrado C, Binlich F, San-Miguel JF. Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment. Blood. 2016 Feb 11;127(6):713-21. Epub 2015 Dec 2. [http://www.bloodjournal.org/content/127/6/713.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760132/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26631116 PubMed]
 
−
## '''Update:''' San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Günther A, Nakorn TN, Siritanaratkul N, Schlossman RL, Hou J, Moreau P, Lonial S, Lee JH, Einsele H, Sopala M, Bengoudifa BR, Binlich F, Richardson PG. Overall survival of patients with relapsed multiple myeloma treated with panobinostat or placebo plus bortezomib and dexamethasone (the PANORAMA 1 trial): a randomised, placebo-controlled, phase 3 trial. Lancet Haematol. 2016 Nov;3(11):e506-e515. Epub 2016 Oct 14. [https://doi.org/10.1016/S2352-3026(16)30147-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27751707 PubMed]
 
−
==B-Pd {{#subobject:95u8g1|Regimen=1}}==
 
−
B-Pd: '''<u>B</u>'''ortezomib, '''<u>P</u>'''omalidomide, low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:57e4a5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Awaiting publication (DREAMM 8)
 
−
|2020-2023
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Pd_.26_Belantamab_mafodotin_66|Pd & Belantamab mafodotin]]
 
−
|style="background-color:#d3d3d3"|TBD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]]
 
−
*[[Pomalidomide (Pomalyst)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]]
 
−
</div></div>
 
−
===References===
 
−
#'''DREAMM 8:''' NCT04484623
 
−
==BTD {{#subobject:95a10c|Regimen=1}}==
 
−
BTD: '''<u>B</u>'''endamustine, '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:57e4a5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13435 Schey et al. 2015 (MUKone)]
 
−
|2011-2012
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-de-esc)
 
−
|[[#BTD|BTD]]; higher-dose benadmustine
 
−
|style="background-color:#d3d3d3"|Not reported<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>While this study was randomized, it was "not powered to directly compare the two arms for statistically significant superiority."''<br>
 
−
''Note: This study involved two doses of bendamustine but the higher dose was too toxic, leading to premature closure. Note that dosage listed is the lower dose. Also, the abstracts says that thalidomide is given days 1 to 21 but the body of the paper says days 1 to 28.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 8, 15, 22
 
−
====Targeted therapy====
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 21 (see note)
 
−
====Supportive therapy====
 
−
*Thromboprophylaxis (not specified)
 
−
*Anti-infective prophylaxis (not specified)
 
−
'''28-day cycle for 6 to 9 cycles (2 cycles past best response)'''
 
−
</div></div>
 
−
===References===
 
−
# '''MUKone:''' Schey S, Brown SR, Tillotson AL, Yong K, Williams C, Davies F, Morgan G, Cavenagh J, Cook G, Cook M, Orti G, Morris C, Sherratt D, Flanagan L, Gregory W, Cavet J; Myeloma UK Early Phase Clinical Trial Network. Bendamustine, thalidomide and dexamethasone combination therapy for relapsed/refractory myeloma patients: results of the MUKone randomized dose selection trial. Br J Haematol. 2015 Aug;170(3):336-48. Epub 2015 Apr 20. [https://doi.org/10.1111/bjh.13435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25891006 PubMed] ISRCTN90889843
 
−
 
−
==CPR {{#subobject:cbf3b8|Regimen=1}}==
 
−
CPR: '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone, '''<u>R</u>'''evlimid (Lenalidomide)
 
−
<br>REP: '''<u>R</u>'''evlimid (Lenalidomide), '''<u>E</u>'''ndoxan (Cyclophosphamide), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, "REP" {{#subobject:ea6c95|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/128/19/2297.long Nijhof et al. 2016 (REPEAT)]
 
−
|2011-2014
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|-
 
−
|}
 
−
''Note: Details are for the MTD/phase 2 portion of the published phase 1/2 trial.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 20 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, "CPR" {{#subobject:a8e16f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13100 Reece et al. 2014]
 
−
|2007-2009
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|-
 
−
|}
 
−
''Note: Details are for the phase 2 portion of the published phase 1/2 trial.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> PO on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once every other day
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Reece DE, Masih-Khan E, Atenafu EG, Jimenez-Zepeda VH, Anglin P, Chen C, Kukreti V, Mikhael JR, Trudel S. Phase I-II trial of oral cyclophosphamide, prednisone and lenalidomide for the treatment of patients with relapsed and refractory multiple myeloma. Br J Haematol. 2015 Jan;168(1):46-54. Epub 2014 Aug 22. [https://doi.org/10.1111/bjh.13100 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25146584 PubMed]
 
−
# '''REPEAT:''' Nijhof IS, Franssen LE, Levin MD, Bos GM, Broijl A, Klein SK, Koene HR, Bloem AC, Beeker A, Faber LM, van der Spek E, Ypma PF, Raymakers R, van Spronsen DJ, Westerweel PE, Oostvogels R, van Velzen J, van Kessel B, Mutis T, Sonneveld P, Zweegman S, Lokhorst HM, van de Donk NW. Phase 1/2 study of lenalidomide combined with low-dose cyclophosphamide and prednisone in lenalidomide-refractory multiple myeloma. Blood. 2016 Nov;128(19), 2297-2306. Epub 2016 Sep 19. [http://www.bloodjournal.org/content/128/19/2297.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27647864 PubMed] NCT01352338
 
−
 
−
==CRD {{#subobject:c9ad0a|Regimen=1}}==
 
−
CRD: '''<u>Cy</u>'''clophosphamide, '''<u>R</u>'''evlimid (Lenalidomide), '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:81692e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2010.08250.x Schey et al. 2010]
 
−
|NR
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|-
 
−
|}
 
−
''Note: This is the MTD of this phase 1/2 trial.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg PO once per day on days 1 & 8
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4, 8 to 11
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 75 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Schey SA, Morgan GJ, Ramasamy K, Hazel B, Ladon D, Corderoy S, Jenner M, Phekoo K, Boyd K, Davies FE. The addition of cyclophosphamide to lenalidomide and dexamethasone in multiply relapsed/refractory myeloma patients; a phase I/II study. Br J Haematol. 2010 Aug;150(3):326-33. [https://doi.org/10.1111/j.1365-2141.2010.08250.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20553268 PubMed]
 
−
==CTD {{#subobject:5d7a75|Regimen=1}}==
 
−
CTD: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:57a0c2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1038/sj.thj.6200326 Dimopoulos et al. 2004]
 
−
|NR in abstract
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 150 mg/m<sup>2</sup> PO every 12 hours (before meals) on days 1 to 5
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 3: 20 mg PO every morning after breakfast on days 1 to 5, 14 to 18
 
−
**Cycle 4 onwards: 20 mg PO every morning after breakfast on days 1 to 5
 
−
====Targeted therapy====
 
−
*[[Thalidomide (Thalomid)]] as follows:
 
−
**Cycles 1 to 3: 400 mg PO every evening on days 1 to 5, 14 to 18
 
−
**Cycle 4 onwards: 400 mg PO every evening on days 1 to 5
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Dimopoulos MA, Hamilos G, Zomas A, Gika D, Efstathiou E, Grigoraki V, Poziopoulos C, Xilouri I, Zorzou MP, Anagnostopoulos N, Anagnostopoulos A. Pulsed cyclophosphamide, thalidomide and dexamethasone: an oral regimen for previously treated patients with multiple myeloma. Hematol J. 2004;5(2):112-7. [https://doi.org/10.1038/sj.thj.6200326 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15048060 PubMed]
 
−
==Dara-Kd {{#subobject:0eug87|Regimen=1}}==
 
−
Dara-Kd: '''<u>Dara</u>'''tumumab, '''<u>K</u>'''yprolis (Carfilzomib), low-dose '''<u>d</u>'''examethasone
 
−
<br>D-Kd: '''<u>D</u>'''aratumumab, '''<u>K</u>'''yprolis (Carfilzomib), low-dose '''<u>d</u>'''examethasone
 
−
<br>KdD: '''<u>K</u>'''yprolis (Carfilzomib), low-dose '''<u>d</u>'''examethasone, '''<u>D</u>'''aratumumab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:5cbf82|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(20)30734-0 Dimopoulos et al. 2020 (CANDOR)]
 
−
|2017-2018
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#Carfilzomib_.26_Dexamethasone_.28Kd.29|Kd]]
 
−
|style="background-color:#1a9850"|Superior PFS<sup>1</sup><br>Median PFS: 28.6 vs 15.2 mo<br>(HR 0.59, 95% CI 0.45-0.78)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update.''<br>
 
−
''Note: this dosing if for patients 75 or younger; the steroid dosing is fairly complex; refer to page 45 of the protocol for additional details.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab (Darzalex)]] as follows:
 
−
**Cycle 1: 8 mg/kg IV once per day on days 1 & 2, then 16 mg/kg IV once per day on days 8, 15, 22
 
−
**Cycle 2: 16 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 16 mg/kg IV once per day on days 1 & 15
 
−
**Cycle 7 onwards: 16 mg/kg IV once on day 1
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 2, then 56 mg/m<sup>2</sup> IV over 30 minutes once per day on days 8, 9, 15, 16
 
−
**Cycle 2 onwards: 56 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:5cbf82|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(20)30734-0 Dimopoulos et al. 2020 (CANDOR)]
 
−
|2017-2018
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#Carfilzomib_.26_Dexamethasone_.28Kd.29|Kd]]
 
−
|style="background-color:#1a9850"|Superior PFS<sup>1</sup><br>Median PFS: 28.6 vs 15.2 mo<br>(HR 0.59, 95% CI 0.45-0.78)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update.''<br>
 
−
''Note: this dosing if for patients older than 75; the steroid dosing is fairly complex; refer to page 45 of the protocol for additional details.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab (Darzalex)]] as follows:
 
−
**Cycle 1: 8 mg/kg IV once per day on days 1 & 2, then 16 mg/kg IV once per day on days 8, 15, 22
 
−
**Cycle 2: 16 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 16 mg/kg IV once per day on days 1 & 15
 
−
**Cycle 7 onwards: 16 mg/kg IV once on day 1
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 2, then 56 mg/m<sup>2</sup> IV over 30 minutes once per day on days 8, 9, 15, 16
 
−
**Cycle 2 onwards: 56 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycle 1: 20 mg IV or PO once per day on days 1, 2, 8, then 8 mg IV or PO once on day 9, then 20 mg IV or PO once on day 15, then 8 mg IV or PO once on day 16, then 20 mg IV or PO once on day 22
 
−
**Cycle 2 onwards: 20 mg IV or PO once per day on days 1, 8, 15, 22
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3 {{#subobject:d6utcc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6676132/ Chari et al. 2019 (EQUULEUS)]
 
−
|2014-NR
 
−
|style="background-color:#91cf61"|Phase 1b (RT)
 
−
|ORR: 84%
 
−
|-
 
−
|}
 
−
''Note: this dosing is for patients 75 or younger.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab (Darzalex)]] as follows:
 
−
**Cycles 1 & 2: 16 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 16 mg/kg IV once per day on days 1 & 15
 
−
**Cycle 7 onwards: 16 mg/kg IV once on day 1
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV once on day 1, then 70 mg/m<sup>2</sup> IV once per day on days 8 & 15
 
−
**Cycle 2 onwards: 70 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per infusion, prior to [[Daratumumab (Darzalex)]]
 
−
**For patients receiving the 40 mg/wk dose, the remainder is given the day after the infusion
 
−
*[[Acetaminophen (Tylenol)]] once per infusion, prior to [[Daratumumab (Darzalex)]]
 
−
*[[Diphenhydramine (Benadryl)]] once per infusion, prior to [[Daratumumab (Darzalex)]]
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3 {{#subobject:d67tyg|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6676132/ Chari et al. 2019 (EQUULEUS)]
 
−
|2014-NR
 
−
|style="background-color:#91cf61"|Phase 1b (RT)
 
−
|ORR: 84%
 
−
|-
 
−
|}
 
−
''Note: this dosing is for patients older than 75.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab (Darzalex)]] as follows:
 
−
**Cycles 1 & 2: 16 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 16 mg/kg IV once per day on days 1 & 15
 
−
**Cycle 7 onwards: 16 mg/kg IV once on day 1
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV once on day 1, then 70 mg/m<sup>2</sup> IV once per day on days 8 & 15
 
−
**Cycle 2 onwards: 70 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per infusion, prior to [[Daratumumab (Darzalex)]]
 
−
**For patients receiving the 40 mg/wk dose, the remainder is given the day after the infusion
 
−
*[[Acetaminophen (Tylenol)]] once per infusion, prior to [[Daratumumab (Darzalex)]]
 
−
*[[Diphenhydramine (Benadryl)]] once per infusion, prior to [[Daratumumab (Darzalex)]]
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''EQUULEUS:''' Chari A, Martinez-Lopez J, Mateos MV, Bladé J, Benboubker L, Oriol A, Arnulf B, Rodriguez-Otero P, Pineiro L, Jakubowiak A, de Boer C, Wang J, Clemens PL, Ukropec J, Schecter J, Lonial S, Moreau P. Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Blood. 2019 Aug 1;134(5):421-431. Epub 2019 May 21. [http://www.bloodjournal.org/content/134/5/421.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6676132/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31113777 PubMed] NCT01998971
 
−
#'''CANDOR:''' Dimopoulos M, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Yang H, Klippel Z, Zahlten-Kumeli A, Usmani SZ. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020 Jul 18;396(10245):186-197. [https://doi.org/10.1016/s0140-6736(20)30734-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32682484 PubMed] NCT03158688
 
−
##'''Update:''' Usmani SZ, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Gavriatopoulou M, Oriol A, Rabin N, Nooka A, Qi M, Beksac M, Jakubowiak A, Ding B, Zahlten-Kumeli A, Yusuf A, Dimopoulos M. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol. 2022 Jan;23(1):65-76. Epub 2021 Dec 3. [https://doi.org/10.1016/s1470-2045(21)00579-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34871550/ PubMed]
 
−
#'''REMNANT:''' NCT04513639
 
−
==Dara-Kd (SC daratumumab) {{#subobject:geug87|Regimen=1}}==
 
−
Dara-Kd: '''<u>Dara</u>'''tumumab and hyaluronidase, '''<u>K</u>'''yprolis (Carfilzomib), low-dose '''<u>d</u>'''examethasone
 
−
<br>D-Kd: '''<u>D</u>'''aratumumab and hyaluronidase, '''<u>K</u>'''yprolis (Carfilzomib), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5cjzq2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|Awaiting publication (PLEIADES)
 
−
|2018-NR
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
''Note: the only published manuscript describing PLEIADES does not describe this regimen; FDA dosing information does not have full details either. We will fill these details if/when a manuscript is published.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab and hyaluronidase (Darzalex Faspro)]]
 
−
*[[Carfilzomib (Kyprolis)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]]
 
−
</div></div>
 
−
===References===
 
−
#'''PLEIADES:''' NCT03412565
 
−
==Dara-Pd {{#subobject:5538a8|Regimen=1}}==
 
−
Dara-Pd: '''<u>Dara</u>'''tumumab, '''<u>P</u>'''omalidomide, low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d6f1ac|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5570682/ Chari et al. 2017 (EQUULEUS)]
 
−
|2014-NR
 
−
|style="background-color:#91cf61"|Phase 1b (RT)
 
−
|
 
−
| style="background-color:#9ebcda" |ORR: 59% (95% CI, 49-69)
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00128-5 Dimopoulos et al. 2021 (APOLLO)]
 
−
|2017-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Pomalidomide_.26_Dexamethasone_.28Pd.29|Pd]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 12.4 vs 6.9 mo<br>(HR 0.63, 95% CI 0.47-0.85)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*APOLLO: At least 1 prior line of therapy including lenalidomide and a proteasome inhibitor
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab (Darzalex)]] as follows:
 
−
**Cycles 1 & 2: 16 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 16 mg/kg IV once per day on days 1 & 15
 
−
**Cycle 7 onwards: 16 mg/kg IV once on day 1
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] by the following criteria:
 
−
**Standard patients: 40 mg PO once per day on days 1, 8, 15, 22
 
−
**EQUULEUS; Patients older than 75 years or BMI less than 18.5: 20 mg PO once per day on days 1, 8, 15, 22
 
−
**APOLLO; Patients older than 75 years: 20 mg PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*Details are per EQUULEUS:
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per infusion, prior to [[Daratumumab (Darzalex)]]
 
−
**For patients receiving the 40 mg/wk dose, the remainder is given after the infusion on day of infusion
 
−
*[[Acetaminophen (Tylenol)]] once per infusion, prior to [[Daratumumab (Darzalex)]]
 
−
*An [[:Category:Antihistamines|antihistamine]] once per infusion, prior to [[Daratumumab (Darzalex)]]
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''EQUULEUS:''' Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ, Weiss BM, Krishnan A, Lentzsch S, Comenzo R, Wang J, Nottage K, Chiu C, Khokhar NZ, Ahmadi T, Lonial S. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017 Aug 24;130(8):974-981. Epub 2017 Jun 21. [http://www.bloodjournal.org/content/130/8/974.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5570682/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28637662 PubMed] NCT01998971
 
−
# '''APOLLO:''' Dimopoulos MA, Terpos E, Boccadoro M, Delimpasi S, Beksac M, Katodritou E, Moreau P, Baldini L, Symeonidis A, Bila J, Oriol A, Mateos MV, Einsele H, Orfanidis I, Ahmadi T, Ukropec J, Kampfenkel T, Schecter JM, Qiu Y, Amin H, Vermeulen J, Carson R, Sonneveld P; APOLLO Trial Investigators. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Jun;22(6):801-812. [https://doi.org/10.1016/s1470-2045(21)00128-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34087126/ PubMed] NCT03180736
 
−
#'''KarMMa-3:''' NCT03651128
 
−
#'''MAGNETISMM-5:''' NCT05020236
 
−
==Dara-Pd (SC daratumumab) {{#subobject:5gj2g8|Regimen=1}}==
 
−
Dara-Pd: '''<u>Dara</u>'''tumumab and hyaluronidase, '''<u>P</u>'''omalidomide, low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d6jg81|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00128-5 Dimopoulos et al. 2021 (APOLLO)]
 
−
|2017-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Pomalidomide_.26_Dexamethasone_.28Pd.29|Pd]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 12.4 vs 6.9 mo<br>(HR 0.63, 95% CI 0.47-0.85)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*APOLLO: At least 1 prior line of therapy including lenalidomide and a proteasome inhibitor
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab and hyaluronidase (Darzalex Faspro)]] as follows:
 
−
**Cycles 1 & 2: 1800 mg SC once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 1800 mg SC once per day on days 1 & 15
 
−
**Cycle 7 onwards: 1800 mg SC once on day 1
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] by the following criteria:
 
−
**Standard patients: 40 mg PO once per day on days 1, 8, 15, 22
 
−
**Patients older than 75 years: 20 mg PO once per day on days 1, 8, 15, 22
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''APOLLO:''' Dimopoulos MA, Terpos E, Boccadoro M, Delimpasi S, Beksac M, Katodritou E, Moreau P, Baldini L, Symeonidis A, Bila J, Oriol A, Mateos MV, Einsele H, Orfanidis I, Ahmadi T, Ukropec J, Kampfenkel T, Schecter JM, Qiu Y, Amin H, Vermeulen J, Carson R, Sonneveld P; APOLLO Trial Investigators. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Jun;22(6):801-812. [https://doi.org/10.1016/s1470-2045(21)00128-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34087126/ PubMed] NCT03180736
 
−
#'''MajesTEC-3:''' NCT05083169
 
−
==Dara-Rd {{#subobject:0e17f7|Regimen=1}}==
 
−
Dara-Rd: '''<u>Dara</u>'''tumumab, '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<br>D-Rd: '''<u>D</u>'''aratumumab, '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, limited duration {{#subobject:5cbf82|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054695/ Plesner et al. 2016 (GEN503)]
 
−
|2012-NR
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab (Darzalex)]] as follows:
 
−
**Cycles 1 & 2: 16 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 16 mg/kg IV once per day on days 1 & 15
 
−
**Cycle 7 onwards: 16 mg/kg IV once on day 1
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
'''28-day cycle for up to 26 cycles (2 years)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, indefinite {{#subobject:5chgz2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1607751 Dimopoulos et al. 2016 (POLLUX)]
 
−
|2014-2015
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]]
 
−
|style="background-color:#1a9850"|Superior PFS<sup>1</sup><br>Median PFS: 44.5 vs 17.5 mo<br>(HR 0.44, 95% CI 0.35-0.55)
 
−
|-
 
−
|}
 
−
<sup>1</sup>Reported efficacy is based on the 2020 update.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab (Darzalex)]] as follows:
 
−
**Cycles 1 & 2: 16 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 16 mg/kg IV once per day on days 1 & 15
 
−
**Cycle 7 onwards: 16 mg/kg IV once on day 1
 
−
*[[Lenalidomide (Revlimid)]] by the following criteria:
 
−
**Standard patients: 25 mg PO once per day on days 1 to 21
 
−
**Patients with CrCl of 30 to 60 mL/min/1.73m<sup>2</sup>: 10 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] by the following criteria:
 
−
**Standard patients: 40 mg PO once per day on days 1, 8, 15, 22
 
−
**Patients older than 75 years or underweight (BMI less than 18.5): 20 mg PO once per day on days 1, 8, 15, 22
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Torben Plesner, MD, Hendrik-Tobias Arkenau, MD, Henk M. Lokhorst, MD PhD, Peter Gimsing, MD, PhD, Jakub Krejcik, MD, Charlotte Lemech, MD, Monique C. Minnema, MD PhD, Ulrik Lassen, MD PhD, Jacob P. Laubach, MD, Tahamtan Ahmadi, MD, PhD, Howard Yeh, MD, Mary E Guckert, MSN, RN, Huaibao Feng, Nikolai Constantin Brun, MD PhD, Steen Lisby, Linda Basse, MD DMSc, Antonio Palumbo, MD. Safety and Efficacy of Daratumumab with Lenalidomide and Dexamethasone in Relapsed or Relapsed, Refractory Multiple Myeloma. ASH 2014 Abstract 84. [https://ash.confex.com/ash/2014/webprogram/Paper74400.html link to abstract]. -->
 
−
# '''GEN503:''' Plesner T, Arkenau HT, Gimsing P, Krejcik J, Lemech C, Minnema MC, Lassen U, Laubach JP, Palumbo A, Lisby S, Basse L, Wang J, Sasser AK, Guckert ME, de Boer C, Khokhar NZ, Yeh H, Clemens PL, Ahmadi T, Lokhorst HM, Richardson PG. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood. 2016 Oct 6;128(14):1821-8. Epub 2016 Aug 16. [http://www.bloodjournal.org/content/128/14/1821.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054695/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27531679 PubMed] NCT01615029
 
−
# '''POLLUX:''' Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P; POLLUX Investigators. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016 Oct 6;375(14):1319-1331. [https://doi.org/10.1056/NEJMoa1607751 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1607751/suppl_file/nejmoa1607751_protocol.pdf link to original protocol] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27705267 PubMed] NCT02076009
 
−
## '''Update:''' Dimopoulos MA, San-Miguel J, Belch A, White D, Benboubker L, Cook G, Leiba M, Morton J, Ho PJ, Kim K, Takezako N, Moreau P, Kaufman JL, Sutherland HJ, Lalancette M, Magen H, Iida S, Kim JS, Prince HM, Cochrane T, Oriol A, Bahlis NJ, Chari A, O' Rourke L, Wu K, Schecter JM, Casneuf T, Chiu C, Soong D, Sasser AK, Khokhar NZ, Avet-Loiseau H, Usmani SZ. Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Haematologica. 2018 Dec;103(12):2088-96. Epub 2018 Sep 20. [https://doi.org/10.3324/haematol.2018.194282 link to original article]  [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6269302/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30237262 PubMed]
 
−
## '''Update:''' Bahlis NJ, Dimopoulos MA, White DJ, Benboubker L, Cook G, Leiba M, Ho PJ, Kim K, Takezako N, Moreau P, Kaufman JL, Krevvata M, Chiu C, Qin X, Okonkwo L, Trivedi S, Ukropec J, Qi M, San-Miguel J. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia. 2020 Jul;34(7):1875-1884. Epub 2020 Jan 30. [https://doi.org/10.1038/s41375-020-0711-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7326710/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32001798 PubMed]
 
−
#'''CONFIRM<sub>MM</sub>:''' NCT03836014
 
−
==Dara-Rd (SC daratumumab) {{#subobject:5cugh1|Regimen=1}}==
 
−
Dara-Rd: '''<u>Dara</u>'''tumumab and hyaluronidase, '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<br>D-Rd: '''<u>D</u>'''aratumumab and hyaluronidase, '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e15b5d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.16980 Chari et al. 2020 (PLEIADES)]
 
−
|2018-NR
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab and hyaluronidase (Darzalex Faspro)]] as follows:
 
−
**Cycles 1 & 2: 1800 mg SC once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 1800 mg SC once per day on days 1 & 15
 
−
**Cycle 7 onwards: 1800 mg SC once on day 1
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''PLEIADES:''' Chari A, Rodriguez-Otero P, McCarthy H, Suzuki K, Hungria V, Sureda Balari A, Perrot A, Hulin C, Magen H, Iida S, Maisnar V, Karlin L, Pour L, Parasrampuria DA, Masterson T, Kosh M, Yang S, Delioukina M, Qi M, Carson R, Touzeau C. Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): an open-label Phase II study. Br J Haematol. 2021 Mar;192(5):869-878. Epub 2020 Jul 30. [https://doi.org/10.1111/bjh.16980 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33216361/ PubMed] NCT03412565
 
−
==Dara-Vd {{#subobject:5770be|Regimen=1}}==
 
−
Dara-Vd: '''<u>Dara</u>'''tumumab, '''<u>V</u>'''elcade (Bortezomib), low-dose '''<u>d</u>'''examethasone
 
−
<br>D-Vd: '''<u>D</u>'''aratumumab, '''<u>V</u>'''elcade (Bortezomib), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:18a80b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1606038 Palumbo et al. 2016 (CASTOR)]
 
−
|2014-2015
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Vd]]
 
−
|style="background-color:#1a9850"|Superior PFS<sup>1</sup><br>Median PFS: 16.7 vs 7.1 mo<br>(HR 0.31, 95% CI 0.25-0.40)
 
−
|-
 
−
|[https://doi.org/10.1016/j.clml.2021.04.012 Lu et al. 2021 (LEPUS)]
 
−
|2017-2019
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Vd]]
 
−
|style="background-color:#1a9850"|Superior PFS<br>Median PFS: NYR vs 6.3 mo<br>(HR 0.28, 95% CI 0.17-0.47)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2019 update.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*CASTOR & LEPUS: At least 1 prior line of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab (Darzalex)]] as follows:
 
−
**Cycles 1 to 3: 16 mg/kg IV once per day on days 1, 8, 15
 
−
**Cycle 4 onwards: 16 mg/kg IV once on day 1
 
−
*[[Bortezomib (Velcade)]] as follows:
 
−
**Cycles 1 to 8: 1.3 mg/m<sup>2</sup> SC once per day on days 1, 4, 8, 11
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 8: 20 mg IV or PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
***Can be dose-reduced to 20 mg IV or PO once per day on days 1, 8, 15 for patients greater than 75 years, with BMI less than 18.5, or with previous side effects
 
−
'''21-day cycle for 8 cycles, then 28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # ASCO 2016 Abstract LBA4 -->
 
−
# '''CASTOR:''' Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Qi M, Schecter J, Amin H, Qin X, Deraedt W, Ahmadi T, Spencer A, Sonneveld P; CASTOR Investigators. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016 Aug 25;375(8):754-66. [https://doi.org/10.1056/NEJMoa1606038 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1606038/suppl_file/nejmoa1606038_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27557302 PubMed] NCT02136134
 
−
## '''Update:''' Spencer A, Lentzsch S, Weisel K, Avet-Loiseau H, Mark TM, Spicka I, Masszi T, Lauri B, Levin MD, Bosi A, Hungria V, Cavo M, Lee JJ, Nooka AK, Quach H, Lee C, Barreto W, Corradini P, Min CK, Scott EC, Chanan-Khan AA, Horvath N, Capra M, Beksac M, Ovilla R, Jo JC, Shin HJ, Sonneveld P, Soong D, Casneuf T, Chiu C, Amin H, Qi M, Thiyagarajah P, Sasser AK, Schecter JM, Mateos MV. Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Haematologica. 2018 Dec;103(12):2079-87. Epub 2018 Sep 20. [http://www.haematologica.org/content/103/12/2079 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6269293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30237264 PubMed]
 
−
## '''Update:''' Mateos MV, Sonneveld P, Hungria V, Nooka AK, Estell JA, Barreto W, Corradini P, Min CK, Medvedova E, Weisel K, Chiu C, Schecter JM, Amin H, Qin X, Ukropec J, Kobos R, Spencer A. Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR. Clin Lymphoma Myeloma Leuk. 2020 Aug;20(8):509-518. Epub 2019 Oct 9. [https://doi.org/10.1016/j.clml.2019.09.623 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32482541/ PubMed]
 
−
# '''LEPUS:''' Lu J, Fu W, Li W, Hu J, An G, Wang Y, Fu C, Chen L, Jin J, Cen X, Ge Z, Cai Z, Niu T, Qi M, Sun S, Gai X, Liu W, Liu W, Yang X, Huang X. Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Chinese Patients with Relapsed or Refractory Multiple Myeloma: Phase 3 LEPUS (MMY3009) Study. Clin Lymphoma Myeloma Leuk. 2021 Sep;21(9):e699-e709. Epub 2021 Apr 24. [https://doi.org/10.1016/j.clml.2021.04.012 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34108127/ PubMed] NCT03234972
 
−
#'''EXCALIBER-RRMM:''' NCT04975997
 
−
#'''KarMMa-3:''' NCT03651128
 
−
==Dara-Vd (SC daratumumab) {{#subobject:5igjze|Regimen=1}}==
 
−
Dara-Vd: '''<u>Dara</u>'''tumumab and hyaluronidase, '''<u>V</u>'''elcade (Bortezomib), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:hqec0b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Awaiting publication (MajesTEC-3)
 
−
|2021-2024
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#SC_Daratumumab_.26_Teclistamab_77|Tec-Dara]]
 
−
|style="background-color:#d3d3d3"|TBD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Daratumumab and hyaluronidase (Darzalex Faspro)]]
 
−
*[[Bortezomib (Velcade)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]]
 
−
</div></div>
 
−
===References===
 
−
#'''MajesTEC-3:''' NCT05083169
 
−
==Elo-Pd {{#subobject:149a50 |Regimen=1}}==
 
−
Elo-Pd: '''<u>Elo</u>'''tuzumab, '''<u>P</u>'''omalidomide, low-dose '''<u>d</u>'''examethasone
 
−
<br>EPd: '''<u>E</u>'''lotuzumab, '''<u>P</u>'''omalidomide, low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, lower-dose dexamethasone {{#subobject:a22809 |Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1805762 Dimopoulos et al. 2018 (ELOQUENT-3)]
 
−
|2016-2017
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-RT-esc)
 
−
|[[#Pomalidomide_.26_Dexamethasone_.28Pd.29|Pd]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 10.3 vs 4.7 mo<br>(HR 0.54, 95% CI 0.34-0.86)
 
−
|-
 
−
|}
 
−
''Note: this variant was intended for patients older than 75 years.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*2 or more prior lines of therapy, including lenalidomide and a proteasome inhibitor
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Elotuzumab (Empliciti)]] as follows:
 
−
**Cycles 1 & 2: 10 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycle 3 onwards: 20 mg/kg IV once on day 1
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Weeks without elotuzumab: 20 mg PO once per week
 
−
**Weeks with elotuzumab: 8 mg PO once per infusion, prior to elotuzumab, then 8 mg IV once per infusion, on days when elotuzumab is administered
 
−
***According to the elotuzumab package insert, the first dose should be given between 3 and 24 hours before elotuzumab; the second dose should be given 45 to 90 minutes before elotuzumab.
 
−
====Supportive therapy====
 
−
*[[Diphenhydramine (Benadryl)]] 25 to 50 mg (route not specified) or its equivalent once per infusion, 45 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
*[[Ranitidine (Zantac)]] 50 mg (route not specified) or its equivalent once per infusion, 45 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
*[[Acetaminophen (Tylenol)]] 650 to 1000 mg (route not specified) once per infusion, 45 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
*"Thromboembolic prophylaxis was required "according to institutional guidelines or at the discretion of the investigator."
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, standard-dose dexamethasone {{#subobject:a33209 |Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1805762 Dimopoulos et al. 2018 (ELOQUENT-3)]
 
−
|2016-2017
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
 
−
|[[#Pomalidomide_.26_Dexamethasone_.28Pd.29|Pd]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 10.3 vs 4.7 mo<br>(HR 0.54, 95% CI 0.34-0.86)
 
−
|-
 
−
|}
 
−
''Note: this variant was intended for patients up to 75 years.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*2 or more prior lines of therapy, including lenalidomide and a proteasome inhibitor
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Elotuzumab (Empliciti)]] as follows:
 
−
**Cycles 1 & 2: 10 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycle 3 onwards: 20 mg/kg IV once on day 1
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Weeks without elotuzumab: 40 mg PO once per week
 
−
**Weeks with elotuzumab: 28 mg PO once per infusion, prior to elotuzumab, then 8 mg IV once per infusion, on days when elotuzumab is administered
 
−
***According to the elotuzumab package insert, the first dose should be given between 3 and 24 hours before elotuzumab; the second dose should be given 45 to 90 minutes before elotuzumab.
 
−
====Supportive therapy====
 
−
*[[Diphenhydramine (Benadryl)]] 25 to 50 mg (route not specified) or its equivalent once per infusion, 45 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
*[[Ranitidine (Zantac)]] 50 mg (route not specified) or its equivalent once per infusion, 45 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
*[[Acetaminophen (Tylenol)]] 650 to 1000 mg (route not specified) once per infusion, 45 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
*"Thromboembolic prophylaxis was required "according to institutional guidelines or at the discretion of the investigator."
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''ELOQUENT-3:''' Dimopoulos MA, Dytfeld D, Grosicki S, Moreau P, Takezako N, Hori M, Leleu X, LeBlanc R, Suzuki K, Raab MS, Richardson PG, Popa McKiver M, Jou YM, Shelat SG, Robbins M, Rafferty B, San-Miguel J. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018 Nov 8;379(19):1811-1822. [https://doi.org/10.1056/NEJMoa1805762 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30403938 PubMed] NCT02654132
 
−
#'''EMN29:''' NCT05028348
 
−
#'''KarMMa-3:''' NCT03651128
 
−
==Elo-Rd {{#subobject:b79daa |Regimen=1}}==
 
−
Elo-Rd: '''<u>Elo</u>'''tuzumab, '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<br>ELd: '''<u>E</u>'''lotuzumab, '''<u>L</u>'''enalidomide, low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f2d044 |Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2011.37.2649 Lonial et al. 2012 (1703 Study)]
 
−
|2008-NR
 
−
|style="background-color:#1a9851"|Phase 1b/2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1505654 Lonial et al. 2015 (ELOQUENT-2)]
 
−
|2011-2012
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]]
 
−
|style="background-color:#91cf60"|Seems to have superior OS<sup>1</sup><br>Median OS: 48.3 vs 39.6 mo<br>(HR 0.82, 95.4% CI 0.68-1.00)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for ELOQUENT-2 is based on the 2020 final update.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*ELOQUENT-2: 1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Elotuzumab (Empliciti)]] as follows:
 
−
**Cycles 1 & 2: 10 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycle 3 onwards: 10 mg/kg IV once per day on days 1 & 15
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Weeks without elotuzumab: 40 mg PO once per week
 
−
**Weeks with elotuzumab: 28 mg PO once per infusion, prior to elotuzumab, then 8 mg IV once per infusion, after elotuzumab is administered
 
−
***According to the elotuzumab package insert, the 28 mg PO dose should be given between 3 and 24 hours before elotuzumab; the 8 mg IV dose should be given 45 to 90 minutes before elotuzumab.
 
−
====Supportive therapy====
 
−
*[[Diphenhydramine (Benadryl)]] 25 to 50 mg (route not specified) or its equivalent once per infusion, 30 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
*[[Ranitidine (Zantac)]] 50 mg (route not specified) or its equivalent one per infusion, 30 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
*[[Acetaminophen (Tylenol)]] 650 to 1000 mg (route not specified) or its equivalent once per infusion, 30 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
*"Thromboembolic prophylaxis (e.g., aspirin, low-molecular-weight heparin, or vitamin K antagonists) was administered according to institutional guidelines or at the discretion of the investigator."
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Richardson, Paul G., Jagannath, Sundar, Moreau, Philippe, Jakubowiak, Andrzej, Raab, Marc S, Facon, Thierry, Vij, Ravi, White, Darrell J., Reece, Donna, Benboubker, Lotfi, Zonder, Jeffrey A., Deng, Wei, Kroog, Glenn, Singhal, Anil K, Lonial, Sagar. A Phase 2 Study of Elotuzumab (Elo) in Combination with Lenalidomide and Low-Dose Dexamethasone (Ld) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (R/R MM): Updated Results. ASH Annual Meeting Abstracts 2012 120: 202 -->
 
−
# '''1703 Study:''' Lonial S, Vij R, Harousseau JL, Facon T, Moreau P, Mazumder A, Kaufman JL, Leleu X, Tsao LC, Westland C, Singhal AK, Jagannath S. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol. 2012 Jun 1;30(16):1953-9. [https://doi.org/10.1200/jco.2011.37.2649 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22547589 PubMed] NCT00742560
 
−
<!-- ## '''Abstract: Update:''' Paul G. Richardson, Sundar Jagannath, MD, Philippe Moreau, MD, Andrzej Jakubowiak, MD, PhD, Marc S Raab, MD, PhD, Thierry Facon, MD, Ravi Vij, MBBS, MD, Darrell White, MD, Donna E. Reece, MD, Lotfi Benboubker, MD, PhD, Jeffrey Zonder, MD, L. Claire Tsao, PhD, Kenneth C. Anderson, MD, Eric Bleickardt, MD, Anil K Singhal, MD and Sagar Lonial, MD. Final Results for the 1703 Phase 1b/2 Study of Elotuzumab in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma. ASH 2014 Abstract 302 [https://ash.confex.com/ash/2014/webprogram/Paper74278.html link to abstract] -->
 
−
## '''Update:''' Richardson PG, Jagannath S, Moreau P, Jakubowiak AJ, Raab MS, Facon T, Vij R, White D, Reece DE, Benboubker L, Zonder J, Tsao LC, Anderson KC, Bleickardt E, Singhal AK, Lonial S; 1703 study investigators. Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation study. Lancet Haematol. 2015 Dec;2(12):e516-27. Epub 2015 Nov 16. [https://doi.org/10.1016/S2352-3026(15)00197-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26686406 PubMed]
 
−
# '''ELOQUENT-2:''' Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, Walter-Croneck A, Moreau P, Mateos MV, Magen H, Belch A, Reece D, Beksac M, Spencer A, Oakervee H, Orlowski RZ, Taniwaki M, Röllig C, Einsele H, Wu KL, Singhal A, San-Miguel J, Matsumoto M, Katz J, Bleickardt E, Poulart V, Anderson KC, Richardson P; ELOQUENT-2 Investigators. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015 Aug 13;373(7):621-31. Epub 2015 Jun 2. [https://doi.org/10.1056/NEJMoa1505654 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26035255 PubMed] NCT01239797
 
−
## '''Update:''' Dimopoulos MA, Lonial S, White D, Moreau P, Palumbo A, San-Miguel J, Shpilberg O, Anderson K, Grosicki S, Spicka I, Walter-Croneck A, Magen H, Mateos MV, Belch A, Reece D, Beksac M, Bleickardt E, Poulart V, Sheng J, Sy O, Katz J, Singhal A, Richardson P. Elotuzumab plus lenalidomide/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT-2 follow-up and post-hoc analyses on progression-free survival and tumour growth. Br J Haematol. 2017 Sep;178(6):896-905. Epub 2017 Jul 5. [https://doi.org/10.1111/bjh.14787 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28677826 PubMed]
 
−
## '''Update:''' Dimopoulos MA, Lonial S, Betts KA, Chen C, Zichlin ML, Brun A, Signorovitch JE, Makenbaeva D, Mekan S, Sy O, Weisel K, Richardson PG. Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended 4-year follow-up and analysis of relative progression-free survival from the randomized ELOQUENT-2 trial. Cancer. 2018 Oct 15;124(20):4032-4043. Epub 2018 Sep 11. [https://doi.org/10.1002/cncr.31680 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30204239 PubMed]
 
−
## '''Update:''' Dimopoulos MA, Lonial S, White D, Moreau P, Weisel K, San-Miguel J, Shpilberg O, Grosicki S, Špička I, Walter-Croneck A, Magen H, Mateos MV, Belch A, Reece D, Beksac M, Spencer A, Oakervee H, Orlowski RZ, Taniwaki M, Röllig C, Einsele H, Matsumoto M, Wu KL, Anderson KC, Jou YM, Ganetsky A, Singhal AK, Richardson PG. Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study. Blood Cancer J. 2020 Sep 4;10(9):91. [https://doi.org/10.1038/s41408-020-00357-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474076/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32887873/ PubMed]
 
−
==Elo-Vd {{#subobject:165bf3|Regimen=1}}==
 
−
Elo-Vd: '''<u>Elo</u>'''tuzumab, '''<u>V</u>'''elcade (Bortezomib), low-dose '''<u>d</u>'''examethasone
 
−
<br>EBd: '''<u>E</u>'''lotuzumab, '''<u>B</u>'''ortezomib, low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ad710b |Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900953/ Jakubowiak et al. 2016 (CA204-009)]
 
−
|2012-2013
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Vd]]
 
−
|style="background-color:#d9ef8b"|Might have superior PFS<br>(HR 0.72, 95% CI 0.49-1.06)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*CA204-009: 1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Elotuzumab (Empliciti)]] as follows:
 
−
**Cycles 1 & 2: 10 mg/kg IV once per day on days 1, 8, 15
 
−
**Cycles 3 to 8: 10 mg/kg IV once per day on days 1 & 11
 
−
**Cycle 9 onwards: 10 mg/kg IV once per day on days 1 & 15
 
−
*[[Bortezomib (Velcade)]] as follows:
 
−
**Cycles 1 to 8: 1.3 mg/m<sup>2</sup> IV or SC once per day on days 1, 4, 8, 11
 
−
**Cycle 9 onwards: 1.3 mg/m<sup>2</sup> IV or SC once per day on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 & 2 by the following split schedule:
 
−
***20 mg PO once per day on days 2, 4, 5, 9, 11, 12
 
−
***8 mg PO once per day on days 1, 8, 15, given 3 to 24 hours prior to elotuzumab
 
−
***8 mg IV once per day on days 1, 8, 15, given 45 minutes prior to elotuzumab
 
−
**Cycles 3 to 8 by the following split schedule:
 
−
***20 mg PO once per day on days 2, 4, 5, 8, 9, 12
 
−
***8 mg PO once per day on days 1 & 11, given 3 to 24 hours prior to elotuzumab
 
−
***8 mg IV once per day on days 1 & 11, given 45 minutes prior to elotuzumab
 
−
**Cycle 9 onwards by the following split schedule:
 
−
***20 mg PO once per day on days 2, 8, 9, 16
 
−
***8 mg PO once per day on days 1 & 15, given 3 to 24 hours prior to elotuzumab
 
−
***8 mg IV once per day on days 1 & 15, given 45 minutes prior to elotuzumab
 
−
====Supportive therapy====
 
−
*[[Diphenhydramine (Benadryl)]] 25 to 50 mg (route not specified) once per infusion, 30 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
*[[Ranitidine (Zantac)]] 50 mg (route not specified) once per infusion, 30 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
*[[Acetaminophen (Tylenol)]] 650 to 1000 mg PO once per infusion, 30 to 90 minutes prior to [[Elotuzumab (Empliciti)]]
 
−
'''21-day cycle for 8 cycles, then 28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''CA204-009:''' Jakubowiak A, Offidani M, Pégourie B, De La Rubia J, Garderet L, Laribi K, Bosi A, Marasca R, Laubach J, Mohrbacher A, Carella AM, Singhal AK, Tsao LC, Lynch M, Bleickardt E, Jou YM, Robbins M, Palumbo A. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood. 2016 Jun 9;127(23):2833-40. Epub 2016 Apr 18. [http://www.bloodjournal.org/content/127/23/2833.long link to original article] '''contains dosing details in supplement''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900953/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27091875 PubMed] NCT01478048
 
−
==FRD {{#subobject:69c2ac|Regimen=1}}==
 
−
FRD: '''<u>F</u>'''arydak (Panobinostat), '''<u>R</u>'''evlimid (Lenalidomide), '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:fe3761|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodadvances.org/content/1/19/1575 Chari et al. 2017 (GCO 12-0469)]
 
−
|2012-NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Panobinostat (Farydak)]] 20 mg PO once per day on days 1, 3, 5, 15, 17, 19
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''GCO 12-0469:''' Chari A, Cho HJ, Dhadwal A, Morgan G, La L, Zarychta K, Catamero D, Florendo E, Stevens N, Verina D, Chan E, Leshchenko V, Laganà A, Perumal D, Mei AH, Tung K, Fukui J, Jagannath S, Parekh S. A phase 2 study of panobinostat with lenalidomide and weekly dexamethasone in myeloma. Blood Adv. 2017 Aug 21;1(19):1575-1583. eCollection 2017 Aug 22. [http://www.bloodadvances.org/content/1/19/1575 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728465/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29296798 PubMed] NCT01651039
 
−
==IRd {{#subobject:PYR3|Regimen=1}}==
 
−
IRd: '''<u>I</u>'''xazomib, '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:PYV3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1516282 Moreau et al. 2016 (TOURMALINE-MM1)]
 
−
|2012-2014
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]]
 
−
|style="background-color:#1a9850"|Superior PFS <br>(HR 0.74, 95% CI 0.59-0.94)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500972/ Hou et al. 2017 (TOURMALINE-MM1 China Continuation)]
 
−
|2014-2015
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]]
 
−
|style="background-color:#1a9850"|Superior OS <br>(HR 0.42, 95% CI 0.24-0.73)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*TOURMALINE-MM1 & TOURMALINE-MM1 China Continuation: 1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ixazomib (Ninlaro)]] 4 mg PO once per day on days 1, 8, 15, taken at least one hour before or at least two hours after food
 
−
*[[Lenalidomide (Revlimid)]] by the following laboratory-based criteria:
 
−
**Normal renal function: 25 mg PO once per day on days 1 to 21
 
−
**CrCl of less than or equal to 60 mL/min/1.73m<sup>2</sup> or less than or equal to 50 mL/min/1.73m<sup>2</sup> (depends on local practice): 10 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*Thromboprophylaxis required
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Philippe Moreau, MD, Tamás Masszi, MD, Norbert Grzasko, MD, PhD, Nizar J Bahlis, MD, Markus Hansson, Ludek Pour, MD, Irwindeep Sandhu, MD, Peter Ganly, BMBCh, PhD, Bartrum W Baker, MBChB, FRACP, FRCPA, Sharon Jackson, MBChB, FRACP, FRCPA, Anne-Marie Stoppa, MD, David R Simpson, MBChB, FRACP, FRCPA, Peter Gimsing, MD, DMSci, Antonio Palumbo, Laurent Garderet, MD, Michele Cavo, Shaji K. Kumar, MD, Cyrille Touzeau, MD, Francis Buadi, MD, Jacob P. Laubach, MD, Jianchang Lin, PhD, Deborah Berg, RN, MSN, Alessandra DiBacco, PhD, Ai-Min Hui, MD, PhD and Paul G. Richardson, MD. Ixazomib, an Investigational Oral Proteasome Inhibitor (PI), in Combination with Lenalidomide and Dexamethasone (IRd), Significantly Extends Progression-Free Survival (PFS) for Patients (Pts) with Relapsed and/or Refractory Multiple Myeloma (RRMM): The Phase 3 Tourmaline-MM1 Study (NCT01564537). ASH Annual Meeting 2015 Abstract 727 [https://ash.confex.com/ash/2015/webprogram/Paper79829.html link to abstract] -->
 
−
# '''TOURMALINE-MM1:''' Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Simpson DR, Gimsing P, Palumbo A, Garderet L, Cavo M, Kumar S, Touzeau C, Buadi FK, Laubach JP, Berg DT, Lin J, Di Bacco A, Hui AM, van de Velde H, Richardson PG; TOURMALINE-MM1 Study Group. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016 Apr 28;374(17):1621-1634. [https://doi.org/10.1056/NEJMoa1516282 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27119237 PubMed] NCT01564537
 
−
## '''Subgroup analysis:''' Avet-Loiseau H, Bahlis NJ, Chng WJ, Masszi T, Viterbo L, Pour L, Ganly P, Palumbo A, Cavo M, Langer C, Pluta A, Nagler A, Kumar S, Ben-Yehuda D, Rajkumar SV, San-Miguel J, Berg D, Lin J, van de Velde H, Esseltine DL, di Bacco A, Moreau P, Richardson PG. Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. Blood. 2017 Dec 14;130(24):2610-2618. Epub 2017 Oct 20. [http://www.bloodjournal.org/content/130/24/2610.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/29054911 PubMed]
 
−
## '''Update:''' Richardson PG, Kumar SK, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Gimsing P, Garderet L, Touzeau C, Buadi FK, Laubach JP, Cavo M, Darif M, Labotka R, Berg D, Moreau P. Final Overall Survival Analysis of the TOURMALINE-MM1 Phase III Trial of Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma. J Clin Oncol. 2021 Aug 1;39(22):2430-2442. Epub 2021 Jun 11. [https://doi.org/10.1200/jco.21.00972 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34111952/ PubMed]
 
−
# '''TOURMALINE-MM1 China Continuation:''' Hou J, Jin J, Xu Y, Wu D, Ke X, Zhou D, Lu J, Du X, Chen X, Li J, Liu J, Gupta N, Hanley MJ, Li H, Hua Z, Wang B, Zhang X, Wang H, van de Velde H, Richardson PG, Moreau P. Randomized, double-blind, placebo-controlled phase III study of ixazomib plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma: China Continuation study. J Hematol Oncol. 2017 Jul 6;10(1):137. [https://doi.org/10.1186/s13045-017-0501-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500972/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28683766 PubMed] NCT01564537
 
−
#'''KarMMa-3:''' NCT03651128
 
−
==Isa-Kd {{#subobject:06bt45|Regimen=1}}==
 
−
Isa-Kd: '''<u>Isa</u>'''tuximab, '''<u>K</u>'''yprolis (Carfilzomib), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ed8yy1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(21)00592-4 Moreau et al. 2021 (IKEMA)]
 
−
|2017-2019
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#Carfilzomib_.26_Dexamethasone_.28Kd.29|Kd]]
 
−
| style="background-color:#1a9850" |Superior PFS<sup>1</sup><br>Median PFS: 35.7 vs 19.2 mo<br>(HR 0.58, 99% CI 0.42-0.79)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''<br>
 
−
''Note: Dosing details are from the FDA package insert.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Isatuximab (Sarclisa)]] '''given second''' as follows:
 
−
**Cycle 1: 10 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycle 2 onwards: 10 mg/kg IV once per day on days 1 & 15
 
−
*[[Carfilzomib (Kyprolis)]] '''given third''' as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 2, then 56 mg/m<sup>2</sup> IV over 30 minutes once per day on days 8, 9, 15, 16
 
−
**Cycle 2 onwards: 56 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO or IV once per day on days 1, 2, 8, 9, 15, 16, 22, 23, '''given first'''
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''IKEMA:''' Moreau P, Dimopoulos MA, Mikhael J, Yong K, Capra M, Facon T, Hajek R, Špička I, Baker R, Kim K, Martinez G, Min CK, Pour L, Leleu X, Oriol A, Koh Y, Suzuki K, Risse ML, Asset G, Macé S, Martin T; IKEMA study group. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021 Jun 19;397(10292):2361-2371. Epub 2021 Jun 4. [https://doi.org/10.1016/s0140-6736(21)00592-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34097854/ PubMed] NCT03275285
 
−
##'''Update:''' Martin T, Dimopoulos MA, Mikhael J, Yong K, Capra M, Facon T, Hajek R, Špička I, Casca F, Macé S, Risse ML, Moreau P. MM-064 Updated Progression-Free Survival and Depth of Response in IKEMA, a Randomized Phase 3 Trial of Isatuximab, Carfilzomib, and Dexamethasone (Isa-Kd) Versus Kd in Relapsed Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S403-S404. [https://doi.org/10.1016/s2152-2650(22)01586-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36164137/ PubMed]
 
−
==Isa-Pd {{#subobject:06ba85|Regimen=1}}==
 
−
Isa-Pd: '''<u>Isa</u>'''tuximab, '''<u>P</u>'''omalidomide, low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ed8uu6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(19)32556-5 Attal et al. 2019 (ICARIA-MM)]
 
−
|2017-2018
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#Pomalidomide_.26_Dexamethasone_.28Pd.29|Pd]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup><br>Median OS: 24.6 vs 17.7 mo<br>(HR 0.76, 95% CI 0.57-1.01)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*ICARIA-MM: At least 2 prior lines of therapy including lenalidomide and a proteasome inhibitor
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Isatuximab (Sarclisa)]] as follows:
 
−
**Cycle 1: 10 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycle 2 onwards: 10 mg/kg IV once per day on days 1 & 15
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] by the following age-based criteria:
 
−
**75 or younger: 40 mg PO once per day on days 1, 8, 15, 22
 
−
**Older than 75: 20 mg PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*Mandatory [[Aspirin]] or [[:Category:Low_molecular_weight_heparins||LMWH]]
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''ICARIA-MM:''' Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Macé S, Corzo KP, Campana F, Le-Guennec S, Dubin F, Anderson KC; ICARIA-MM study group. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019 Dec 7;394(10214):2096-2107. Epub 2019 Nov 14. Erratum in: Lancet. 2019 Dec 7;394(10214):2072. [https://doi.org/10.1016/s0140-6736(19)32556-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31735560 PubMed] NCT02990338
 
−
##'''Update:''' Richardson PG, Perrot A, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Malinge L, Dubin F, van de Velde H, Anderson KC. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study. Lancet Oncol. 2022 Mar;23(3):416-427. Epub 2022 Feb 10. [https://doi.org/10.1016/s1470-2045(22)00019-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35151415/ PubMed]
 
−
# '''EFC15951:''' NCT05405166
 
−
==KPD {{#subobject:c7d038|Regimen=1}}==
 
−
KPD: '''<u>K</u>'''yprolis (Carfilzomib), '''<u>P</u>'''omalidomide, '''<u>D</u>'''examethasone
 
−
<br>CPD: '''<u>C</u>'''arfilzomib, '''<u>P</u>'''omalidomide, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1a0484|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643003/ Shah et al. 2015 (PO-MM-PI-0034)]
 
−
|2011-NR
 
−
|style="background-color:#91cf61"|Phase 1
 
−
|-
 
−
|}
 
−
''Note: although this is described as a Phase 1 trial, an additional 20 patients were enrolled at the MTD, which is the dose reported here.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 2, then 27 mg/m<sup>2</sup> IV over 30 minutes once per day on days 8, 9, 15, 16
 
−
**Cycles 2 to 6: 27 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 4: 40 mg IV or PO once per day on days 1, 8, 15, 22
 
−
**Cycles 5 to 6: 20 mg IV or PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*"[[:Category:Antivirals|Anti-viral therapy]]"
 
−
*[[Aspirin]] 81 mg PO once per day
 
−
**[[:Category:Low molecular weight heparins|Low molecular weight heparin]] was used in patients intolerant of aspirin
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#KPD_2|KPD]] maintenance
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Jatin J. Shah, MD, Edward A. Stadtmauer, MD, Rafat Abonour, MD, Adam D. Cohen, MD, William I. Bensinger, MD, Cristina Gasparetto, MD, Jonathan L. Kaufman, MD, Suzanne Lentzsch, MD, Dan T. Vogl, MD, Robert Z. Orlowski, MD, PhD, Erica L. Kim, MPH, Marti McKinley, BSN, MBA, Brian G.M. Durie, MD. A Multi-Center Phase I/II Trial of Carfilzomib and Pomalidomide with Dexamethasone (Car-Pom-d) in Patients with Relapsed/Refractory Multiple Myeloma. 2013 ASH Annual Meeting abstract 690. [http://www.myelomabeacon.com/resources/mtgs/ash2013/abs/690/ link to abstract] [http://myeloma.org/pdfs/Shah-74-3909.pdf link to presentation] '''contains dosing details in manuscript''' -->
 
−
# '''PO-MM-PI-0034:''' Shah JJ, Stadtmauer EA, Abonour R, Cohen AD, Bensinger WI, Gasparetto C, Kaufman JL, Lentzsch S, Vogl DT, Gomes CL, Pascucci N, Smith DD, Orlowski RZ, Durie BG. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015 Nov 12;126(20):2284-90. Epub 2015 Sep 17. [http://www.bloodjournal.org/content/126/20/2284.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643003/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26384354 PubMed] NCT01464034
 
−
 
−
==KRd {{#subobject:dec1da|Regimen=1}}==
 
−
KRd: '''<u>K</u>'''yprolis (Carfilzomib), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<br>CRd: '''<u>C</u>'''arfilzomib, '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, bi-weekly carfilzomib {{#subobject:de433f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814729/ Wang et al. 2013 (PX-171-006)]
 
−
|2008-2010
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1411321 Stewart et al. 2014 (ASPIRE)]
 
−
|2010-2012
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]]
 
−
|style="background-color:#1a9850"|Superior OS<sup>1</sup> <br>(HR 0.79, 95% CI 0.67-0.95)
 
−
|style="background-color:#1a9850"|Superior GHS/QoL
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for ASPIRE is based on the 2018 update.''<br>
 
−
''Note: In PX-171-006, patients with at least SD after 4 cycles received up to 12 cycles; patients with at least SD after 12 cycles received up to 18 cycles.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*ASPIRE: 1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1 & 2, then 27 mg/m<sup>2</sup> IV over 10 minutes once per day on days 8, 9, 15, 16
 
−
**Cycles 2 to 12: 27 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1, 2, 8, 9, 15, 16
 
−
**Cycles 13 to 18: 27 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1, 2, 15, 16
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*[[Valacyclovir (Valtrex)]] (dose not specified) or equivalent [[:Category:Antivirals|antiviral]] while taking [[Lenalidomide (Revlimid)]]
 
−
*[[Aspirin]] (dose not specified) or other [[:Category:Anticoagulants|anticoagulant]] or [[:Category:Antiplatelet_agents|antiplatelet]] medication such as [[Clopidogrel (Plavix)]], [[:Category:Low_molecular_weight_heparins|low-molecular-weight heparin]] or [[Warfarin (Coumadin)]] while taking [[Lenalidomide (Revlimid)]]
 
−
*[[:Category:Bisphosphonates|Bisphosphonates]] while taking [[Dexamethasone (Decadron)]]
 
−
*[[Lansoprazole (Prevacid)]] (dose not specified) or other [[:Category:Proton_pump_inhibitors|proton pump inhibitor]] while taking [[Dexamethasone (Decadron)]]
 
−
*A prophylactic antibiotic ([[Ciprofloxacin (Cipro)]], [[Amoxicillin]], [[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] are given as examples)
 
−
'''28-day cycle for 18 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*ASPIRE, no progression: [[#Lenalidomide_.26_Dexamethasone_.28Rd.29_88|Rd]] maintenance
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, weekly carfilzomib {{#subobject:b40f55|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593978/ Biran et al. 2019 (CFZ013)]
 
−
|2015-2016
 
−
|style="background-color:#91cf61"|Phase 1b
 
−
|-
 
−
|}
 
−
''Note: this is the dose that is being explored in phase 3 studies.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV once on day 1, then 56 mg/m<sup>2</sup> IV once per day on days 8 & 15
 
−
**Cycles 2 to 18: 56 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 8: 40 mg PO once per day on days 1, 8, 15, 22
 
−
**Cycles 9 to 18: 40 mg PO once per day on days 1, 8, 15
 
−
'''28-day cycle for up to 18 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''PX-171-006:''' Wang M, Martin T, Bensinger W, Alsina M, Siegel DS, Kavalerchik E, Huang M, Orlowski RZ, Niesvizky R. Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood. 2013 Oct 31;122(18):3122-8. Epub 2013 Sep 6. [http://www.bloodjournal.org/content/122/18/3122.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814729/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24014245 PubMed] NCT00603447
 
−
# '''ASPIRE:''' Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, Hájek R, Rosiñol L, Siegel DS, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Wang M, Maisnar V, Minarik J, Bensinger WI, Mateos MV, Ben-Yehuda D, Kukreti V, Zojwalla N, Tonda ME, Yang X, Xing B, Moreau P, Palumbo A; ASPIRE Investigators. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015 Jan 8;372(2):142-52. Epub 2014 Dec 6. [https://doi.org/10.1056/NEJMoa1411321 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25482145 PubMed] NCT01080391
 
−
## '''Subgroup analysis:''' Avet-Loiseau H, Fonseca R, Siegel D, Dimopoulos MA, Špička I, Masszi T, Hájek R, Rosiñol L, Goranova-Marinova V, Mihaylov G, Maisnar V, Mateos MV, Wang M, Niesvizky R, Oriol A, Jakubowiak A, Minarik J, Palumbo A, Bensinger W, Kukreti V, Ben-Yehuda D, Stewart AK, Obreja M, Moreau P. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma. Blood. 2016 Sep 1;128(9):1174-80. Epub 2016 Jul 20. [http://www.bloodjournal.org/content/128/9/1174.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009511/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27439911 PubMed]
 
−
## '''HRQoL analysis:''' Stewart AK, Dimopoulos MA, Masszi T, Špička I, Oriol A, Hájek R, Rosiñol L, Siegel DS, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Buchanan J, Cocks K, Yang X, Xing B, Zojwalla N, Tonda M, Moreau P, Palumbo A. Health-related quality-of-life results from the open-label, randomized, phase III ASPIRE trial evaluating carfilzomib, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed multiple myeloma. J Clin Oncol. 2016 Nov 10;34(32):3921-3930. [https://doi.org/10.1200/JCO.2016.66.9648 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27601539 PubMed]
 
−
## '''Update:''' Siegel DS, Dimopoulos MA, Ludwig H, Facon T, Goldschmidt H, Jakubowiak A, San-Miguel J, Obreja M, Blaedel J, Stewart AK. Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol. 2018 Mar 10;36(8):728-734. Epub 2018 Jan 17. [https://doi.org/10.1200/JCO.2017.76.5032 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29341834 PubMed]
 
−
# '''CFZ013:''' Biran N, Siegel D, Berdeja JG, Raje N, Cornell RF, Alsina M, Kovacsovics T, Fang B, Kimball AS, Landgren O. Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: a phase 1b study. Am J Hematol. 2019 Jul;94(7):794-802. Epub 2019 May 13. [https://doi.org/full/10.1002/ajh.25498 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593978/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31021005 PubMed] NCT02335983
 
−
==PAD {{#subobject:0f85ca|Regimen=1}}==
 
−
PAD: '''<u>P</u>'''S-341 (Bortezomib), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone
 
−
<br>''Note that this regimen is sometimes called VAD but this can create a lot of confusion with the [[Multiple_myeloma_-_historical#VAD|"original" VAD which uses '''<u>V</u>'''incristine]].''
 
−
<br>VAD: '''<u>V</u>'''elcade (Bortezomib), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:34e46e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70245-1 Cook et al. 2014 (NCRI Myeloma X Relapse)]
 
−
|2008-2012
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: length of cycle is not reported in the manuscript, but presumably is 28 days, similar to other PAD regimens.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup> IV once per day on days 1 to 4
 
−
**Could be given as a 4-day continuous infusion or as bolus injections
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycle 1: 40 mg PO once per day on days 1 to 4, 8 to 11, 15 to 18
 
−
**Cycles 2 to 4: 40 mg PO once per day on days 1 to 4
 
−
'''28-day cycle for 2 to 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Melphalan.2C_then_auto_HSCT|High-dose melphalan & autologous hematopoietic cell transplant]] versus weekly oral [[#Cyclophosphamide_monotherapy_88|cyclophosphamide]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''NCRI Myeloma X Relapse:''' Cook G, Williams C, Brown JM, Cairns DA, Cavenagh J, Snowden JA, Ashcroft AJ, Fletcher M, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Chalmers A, O'Connor S, Drayson MT, Morris TC; National Cancer Research Institute Haemato-oncology Clinical Studies Group. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Jul;15(8):874-85. Epub 2014 Jun 16. Erratum in: Lancet Oncol. 2014 Aug;15(9):e365. Dosage error in article text. [https://doi.org/10.1016/S1470-2045(14)70245-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24948586 PubMed] NCT00747877
 
−
## '''Update:''' Cook G, Ashcroft AJ, Cairns DA, Williams CD, Brown JM, Cavenagh JD, Snowden JA, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Pratt G, Chown S, Heartin E, O'Connor S, Drayson MT, Hockaday A, Morris TC; National Cancer Research Institute Haemato-oncology Clinical Studies Group. The effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Lancet Haematol. 2016 Jul;3(7):e340-51. [https://doi.org/10.1016/S2352-3026(16)30049-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27374467 PubMed]
 
−
## '''Subgroup analysis:''' Cook G, Royle KL, O'Connor S, Cairns DA, Ashcroft AJ, Williams CD, Hockaday A, Cavenagh JD, Snowden JA, Ademokun D, Tholouli E, Andrews VE, Jenner M, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Pratt G, Drayson MT, Brown JM, Morris TCM; National Cancer Research Institute Haemato-oncology Clinical Studies Group. The impact of cytogenetics on duration of response and overall survival in patients with relapsed multiple myeloma (long-term follow-up results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Br J Haematol. 2019 May;185(3):450-467. Epub 2019 Feb 6. [https://doi.org/10.1111/bjh.15782 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519200/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30729512 PubMed]
 
−
==PCD {{#subobject:e75204|Regimen=1}}==
 
−
PCD: '''<u>P</u>'''omalidomide, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''examethasone
 
−
<br>PomCyDex: '''<u>Pom</u>'''alidomide, '''<u>Cy</u>'''clophosphamide, '''<u>Dex</u>'''amethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 4/300/40 {{#subobject:d700f5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/132/24/2555.long Garderet et al. 2018 (IC 2013-05)]
 
−
|2014-2017
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg PO once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 4: 40 mg PO once per day on days 1 to 4, 15 to 18
 
−
**Cycle 5 onwards: 40 mg PO once per day on days 1, 8, 15, 22
 
−
'''28-day cycle for 4 to 9 cycles, depending on plan for transplant'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Pomalidomide_.26_Dexamethasone_.28Pd.29_88|Pd]] maintenance
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 4/400/40 {{#subobject:abacf6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/127/21/2561.long Baz et al. 2016 (PO-MM-PI-0039)]
 
−
|2011-2014
 
−
|style="background-color:#1a9851"|Randomized Phase 1/2 (E-esc)
 
−
|[[#Pomalidomide_.26_Dexamethasone_.28Pd.29|Pd]]
 
−
|style="background-color:#91cf60"|Seems to have superior ORR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*PO-MM-PI-0039: At least 2 prior lines of therapy including an immunomodulator; patients were required to be lenalidomide-refractory
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg PO once per day on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] by the following age-based criteria:
 
−
**75 or younger: 40 mg PO once per day on days 1, 8, 15, 22
 
−
**Older than 75: 20 mg PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 81 mg PO once per day unless contraindicated
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the annual meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
 
−
# '''PO-MM-PI-0039:''' Baz RC, Martin TG 3rd, Lin HY, Zhao X, Shain KH, Cho HJ, Wolf JL, Mahindra A, Chari A, Sullivan DM, Nardelli LA, Lau K, Alsina M, Jagannath S. Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 2016 May 26;127(21):2561-8. Epub 2016 Mar 1. Erratum in: Blood. 2016 Jul 21;128(3):461. [http://www.bloodjournal.org/content/127/21/2561.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26932802 PubMed] NCT01432600
 
−
# '''IC 2013-05:''' Garderet L, Kuhnowski F, Berge B, Roussel M, Escoffre-Barbe M, Lafon I, Facon T, Leleu X, Karlin L, Perrot A, Moreau P, Marit G, Stoppa AM, Royer B, Chaleteix C, Tiab M, Araujo C, Lenain P, Macro M, Voog E, Benboubker L, Allangba O, Jourdan E, Orsini-Piocelle F, Brechignac S, Eveillard JR, Belhadj K, Wetterwald M, Pegourie B, Jaccard A, Eisenmann JC, Glaisner S, Mohty M, Hulin C, Loiseau HA, Mathiot C, Attal M. Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma. Blood. 2018 Dec 13;132(24):2555-2563. Epub 2018 Oct 3. [http://www.bloodjournal.org/content/132/24/2555.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30282798 PubMed] NCT02244125
 
−
==PCP {{#subobject:c3aaf2|Regimen=1}}==
 
−
PCP: '''<u>P</u>'''omalidomide, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4a5941|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/122/16/2799.full Larocca et al. 2013 (PO0023)]
 
−
|2010-2012
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|-
 
−
|}
 
−
''Note: Details are for the phase 2 portion of the published phase 1/2 trial.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]] 2.5 mg PO once per day
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once every other day
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 50 mg PO once every other day
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 100 mg PO once per day or [[:Category:Low_molecular_weight_heparins|low-molecular-weight heparin]] "according to patient risk"
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Pomalidomide_.26_Prednisone|Pomalidomide & prednisone]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''PO0023:''' Larocca A, Montefusco V, Bringhen S, Rossi D, Crippa C, Mina R, Galli M, Marcatti M, La Verde G, Giuliani N, Magarotto V, Guglielmelli T, Rota-Scalabrini D, Omedé P, Santagostino A, Baldi I, Carella AM, Boccadoro M, Corradini P, Palumbo A. Pomalidomide, cyclophosphamide and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open label study. Blood. 2013 Oct 17;122(16):2799-806. Epub 2013 Aug 16. [http://www.bloodjournal.org/content/122/16/2799.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23954889 PubMed] NCT01166113
 
−
 
−
==PVD {{#subobject:bf019d|Regimen=1}}==
 
−
PVD: '''<u>P</u>'''omalidomide, '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 21-day cycles {{#subobject:77f644|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(19)30152-4 Richardson et al. 2019 (OPTIMISMM)]
 
−
|2013-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Vd]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11.2 vs 7.1 mo<br>(HR 0.61, 95% CI 0.49-0.77)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*1 to 3 prior lines of therapy including lenalidomide
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 14
 
−
*[[Bortezomib (Velcade)]] as follows:
 
−
**Cycles 1 to 8: 1.3 mg/m<sup>2</sup> IV or SC once per day on days 1, 4, 8, 11
 
−
**Cycle 9 onwards: 1.3 mg/m<sup>2</sup> IV or SC once per day on days 1 & 8
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] by the following criteria:
 
−
**Age up to 75 years, cycles 1 to 8: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
**Age up to 75 years, cycle 9 onwards: 20 mg PO once per day on days 1, 2, 8, 9
 
−
**Older than 75 years, cycles 1 to 8: 10 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
**Older than 75 years, cycle 9 onwards: 10 mg PO once per day on days 1, 2, 8, 9
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 28-day cycles {{#subobject:77f633|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606008/ Paludo et al. 2017 (MC1082)]
 
−
|2012-2014
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
| style="background-color:#e0ecf4" |ORR: 86%
 
−
|-
 
−
|}
 
−
''Note: This is the MTD used in the phase 2 portion of the trial.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV or SC once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 325 mg PO once per day
 
−
**Full dose anticoagulation with [[:Category:Low molecular weight heparins|LMWH]] or [[Warfarin (Coumadin)]] could be substituted at physician discretion
 
−
*[[Acyclovir (Zovirax)]] or equivalent for VZV prophylaxis
 
−
'''28-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Optionally, [[#Pomalidomide_monotherapy_2|pomalidomide]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''MC1082:''' Paludo J, Mikhael JR, LaPlant BR, Halvorson AE, Kumar S, Gertz MA, Hayman SR, Buadi FK, Dispenzieri A, Lust JA, Kapoor P, Leung N, Russell SJ, Dingli D, Go RS, Lin Y, Gonsalves WI, Fonseca R, Bergsagel PL, Roy V, Sher T, Chanan-Khan AA, Ailawadhi S, Stewart AK, Reeder CB, Richardson PG, Rajkumar SV, Lacy MQ. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma. Blood. 2017 Sep 7;130(10):1198-1204. Epub 2017 Jul 6. [http://www.bloodjournal.org/content/130/10/1198.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606008/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28684537 PubMed] NCT01212952
 
−
# '''OPTIMISMM:''' Richardson PG, Oriol A, Beksac M, Liberati AM, Galli M, Schjesvold F, Lindsay J, Weisel K, White D, Facon T, San Miguel J, Sunami K, O'Gorman P, Sonneveld P, Robak P, Semochkin S, Schey S, Yu X, Doerr T, Bensmaine A, Biyukov T, Peluso T, Zaki M, Anderson K, Dimopoulos M; OPTIMISMM trial investigators. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Lancet Oncol. 2019 Jun;20(6):781-794. Epub 2019 May 13. [https://doi.org/10.1016/S1470-2045(19)30152-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31097405 PubMed] NCT01734928
 
−
==RVD {{#subobject:3f1c8e|Regimen=1}}==
 
−
RVD: '''<u>R</u>'''evlimid (Lenalidomide), '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone
 
−
<br>VDR: '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone, '''<u>R</u>'''evlimid (Lenalidomide)
 
−
<br>VRD: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), '''<u>D</u>'''examethasone
 
−
<br>VRd: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bf4291|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123434/ Richardson et al. 2014 (DFCI 06-147)]
 
−
|2006-2008
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|ORR: 64%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 14
 
−
*[[Bortezomib (Velcade)]] 1 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 4: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
**Cycles 5 to 8: 10 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 81 mg or 325 mg PO once per day
 
−
*[[:Category:Antivirals|Antiviral]] therapy for VZV prophylaxis
 
−
'''21-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with SD or better: [[#RVD_2|RVD]] maintenance at previously tolerated dose
 
−
</div></div>
 
−
===References===
 
−
# '''DFCI 06-147:''' Richardson PG, Xie W, Jagannath S, Jakubowiak A, Lonial S, Raje NS, Alsina M, Ghobrial IM, Schlossman RL, Munshi NC, Mazumder A, Vesole DH, Kaufman JL, Colson K, McKenney M, Lunde LE, Feather J, Maglio ME, Warren D, Francis D, Hideshima T, Knight R, Esseltine DL, Mitsiades CS, Weller E, Anderson KC. A phase II trial of lenalidomide, bortezomib and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood. 2014 Mar 6;123(10):1461-9. Epub 2014 Jan 15. [http://www.bloodjournal.org/content/123/10/1461.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123434/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24429336 PubMed] NCT00378209
 
−
==SDd {{#subobject:ghgjgu|Regimen=1}}==
 
−
SDd: '''<u>S</u>'''elinexor, '''<u>D</u>'''aratumumab, low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:48bigz|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9176052/ Gasparetto et al. 2020 (STOMP)]
 
−
|2017-2019
 
−
|style="background-color:#91cf61"|Phase 1/2b, >20 pts in this cohort
 
−
|-
 
−
|}
 
−
''Note: this is the dosing used in the expansion cohort.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Selinexor (Xpovio)]] 100 mg PO once per day on days 1, 8, 15, 22
 
−
*[[Daratumumab (Darzalex)]] as follows:
 
−
**Cycles 1 & 2: 16 mg/kg IV once per day on days 1, 8, 15, 22
 
−
**Cycles 3 to 6: 16 mg/kg IV once per day on days 1 & 15
 
−
**Cycle 7 onwards: 16 mg/kg IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg IV or PO once per day on days 1, 8, 15, 22
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''STOMP:''' Gasparetto C, Lentsch S, Schiller G, Callander N, Tuchman S, Chen C, White D, Kotb R, Sutherland H, Sebag M, Baljevic M, Bensinger W, LeBlanc R, Venner C, Bahlis N, Rossi A, Biran N, Sheehan H, Saint Martin JR, Van Domelen D, Kai K, Shah J, Shacham S, Kauffman M, Lipe B. Selinexor, daratumumab, and dexamethasone in patients with relapsed or refractory multiple myeloma. eJHaem. 2020 Nov 8;2(1):56-65. [https://doi.org/10.1002/jha2.122 link to original article] '''contains dosing details in manuscript''' [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9176052/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35846104/ PubMed] NCT02343042
 
−
==SKd {{#subobject:ghg8e1|Regimen=1}}==
 
−
SKd: '''<u>S</u>'''elinexor, '''<u>K</u>'''yprolis (Carfilzomib), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:48b8ga|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6772147/ Jakubowiak et al. 2019]
 
−
|2014-2016
 
−
| style="background-color:#ffffbe" |Phase 1, <20 pts in this cohort
 
−
|-
 
−
|}
 
−
''Note: this is the RP2D cohort (2b).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Selinexor (Xpovio)]] 60 mg PO once per day on days 1, 3, 8, 10, 15, 17
 
−
*[[Carfilzomib (Kyprolis)]] as follows:
 
−
**Cycle 1: 20 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 27 mg/m<sup>2</sup> IV once per day on days 8, 9, 15, 16
 
−
**Cycles 2 to 8: 27 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9, 15, 16
 
−
**Cycle 9 onwards: 27 mg/m<sup>2</sup> IV once per day on days 1, 2, 15, 16
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 4: 20 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
**Cycle 5 onwards: 10 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Jakubowiak AJ, Jasielec JK, Rosenbaum CA, Cole CE, Chari A, Mikhael J, Nam J, McIver A, Severson E, Stephens LA, Tinari K, Rosebeck S, Zimmerman TM, Hycner T, Turowski A, Karrison T, Zonder JA. Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma. Br J Haematol. 2019 Aug;186(4):549-560. Epub 2019 May 24. [https://doi.org/10.1111/bjh.15969 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6772147/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31124580/ PubMed] NCT02199665
 
−
==SVd {{#subobject:auh402|Regimen=1}}==
 
−
SVd: '''<u>S</u>'''elinexor, '''<u>V</u>'''elcade (Bortezomib), low-dose '''<u>d</u>'''examethasone
 
−
<br>XVd: '''<u>X</u>'''povio (Selinexor), '''<u>V</u>'''elcade (Bortezomib), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6ha3bc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(20)32292-3 Grosicki et al. 2020 (BOSTON)]
 
−
|2017-2019
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Vd]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 13.9 vs 9.5 mo<br>(HR 0.70, 95% CI 0.53-0.93)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*1 to 3 prior lines of therapy, including proteasome inhibitors
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> SC once per day on days 1, 8, 15, 22
 
−
*[[Selinexor (Xpovio)]] 100 mg PO once per day on days 1, 8, 15, 22, 29
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23, 29, 30
 
−
'''35-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''BOSTON:''' Grosicki S, Simonova M, Spicka I, Pour L, Kriachok I, Gavriatopoulou M, Pylypenko H, Auner HW, Leleu X, Doronin V, Usenko G, Bahlis NJ, Hajek R, Benjamin R, Dolai TK, Sinha DK, Venner CP, Garg M, Gironella M, Jurczyszyn A, Robak P, Galli M, Wallington-Beddoe C, Radinoff A, Salogub G, Stevens DA, Basu S, Liberati AM, Quach H, Goranova-Marinova VS, Bila J, Katodritou E, Oliynyk H, Korenkova S, Kumar J, Jagannath S, Moreau P, Levy M, White D, Gatt ME, Facon T, Mateos MV, Cavo M, Reece D, Anderson LD Jr, Saint-Martin JR, Jeha J, Joshi AA, Chai Y, Li L, Peddagali V, Arazy M, Shah J, Shacham S, Kauffman MG, Dimopoulos MA, Richardson PG, Delimpasi S. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020 Nov 14;396(10262):1563-1573. [https://doi.org/10.1016/s0140-6736(20)32292-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33189178/ PubMed] NCT03110562
 
−
# '''BENCH:''' NCT04939142
 
−
==VDC {{#subobject:d412fd|Regimen=1}}==
 
−
VDC: '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone, '''<u>C</u>'''yclophosphamide
 
−
<br>VCD: '''<u>V</u>'''elcade (Bortezomib), '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''examethasone
 
−
<br>CyBorD: '''<u>Cy</u>'''clophosphamide, '''<u>Bor</u>'''tezomib, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:c1252d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s00277-017-3065-z Kropff et al. 2017 (CR015247)]
 
−
|2008-2010
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[#Bortezomib_.26_Dexamethasone_.28Vd.29|Vd]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of TTP <br>(HR 1.41, 95% CI 0.84-2.33)
 
−
|-
 
−
|}
 
−
''Note: Treatment details are from the [https://clinicaltrials.gov/show/NCT00813150 NCT record]. This is an experimental arm that did not meet its primary endpoint.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*1 to 3 prior lines of therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:f35a43|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13653 de Waal et al. 2015]
 
−
|2009-2013
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*Bortezomib-naive
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] as follows:
 
−
**Cycles 1 to 3: 1.3 mg/m<sup>2</sup> IV or SC once per day on days 1, 4, 8, 11
 
−
**Cycles 4 to 6: 1.6 mg/m<sup>2</sup> IV or SC once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 3: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
**Cycles 4 to 6: 20 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day
 
−
====Supportive therapy====
 
−
*Pneumococccal and anti-fungal prophylaxis "according to local protocols"
 
−
*[[Valacyclovir (Valtrex)]] (dose not specified) for herpes prophylaxis
 
−
'''21-day cycle for 3 cycles then 35-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with PR/CR: [[#Bortezomib_.26_Cyclophosphamide|Bortezomib & cyclophosphamide]] maintenance
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3 {{#subobject:d34841|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2007.06656.x Kropff et al. 2007]
 
−
|2004-2005
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*Bortezomib-naive
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] as follows:
 
−
**Cycles 1 to 3: 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
**Cycles 4 to 6: 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 3: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
**Cycles 4 to 6: 20 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
'''21-day cycle for 3 cycles then 35-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Kropff M, Bisping G, Schuck E, Liebisch P, Lang N, Hentrich M, Dechow T, Kröger N, Salwender H, Metzner B, Sezer O, Engelhardt M, Wolf HH, Einsele H, Volpert S, Heinecke A, Berdel WE, Kienast J; Deutsche Studiengruppe Multiples Myelom,. Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br J Haematol. 2007 Aug;138(3):330-7. [https://doi.org/10.1111/j.1365-2141.2007.06656.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17614819 PubMed]
 
−
# de Waal EG, de Munck L, Hoogendoorn M, Woolthuis G, van der Velden A, Tromp Y, Vellenga E, Hovenga S. Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients. Br J Haematol. 2015 Dec;171(5):720-5. Epub 2015 Sep 11. [https://doi.org/10.1111/bjh.13653 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26358087 PubMed]
 
−
# '''CR015247:''' Kropff M, Vogel M, Bisping G, Schlag R, Weide R, Knauf W, Fiechtner H, Kojouharoff G, Kremers S, Berdel WE. Bortezomib and low-dose dexamethasone with or without continuous low-dose oral cyclophosphamide for primary refractory or relapsed multiple myeloma: a randomized phase III study. Ann Hematol. 2017 Nov;96(11):1857-1866. Epub 2017 Sep 14. [https://doi.org/10.1007/s00277-017-3065-z link to original article] [https://pubmed.ncbi.nlm.nih.gov/28905189 PubMed] NCT00813150
 
−
 
−
==VTD {{#subobject:96881b|Regimen=1}}==
 
−
VTD: '''<u>V</u>'''elcade (Bortezomib), '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5ad72e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2011.37.4918 Garderet et al. 2012 (MMVAR/IFM 2005-04)]
 
−
|2006-2010
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[#Thalidomide_.26_Dexamethasone_.28TD.29|TD]]
 
−
|style="background-color:#1a9850"|Superior TTP <br>(HR 0.59, 95% CI 0.44-0.80)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*At least 1 autologous stem-cell transplant
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] as follows:
 
−
**Cycles 1 to 8: 1.3 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 8, 11
 
−
**Cycles 9 to 12: 1.3 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22
 
−
*[[Thalidomide (Thalomid)]] 200 mg PO once per day
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*Primary prophylaxis: [[Enoxaparin (Lovenox)]] 40 mg SC once per day
 
−
*Secondary prophylaxis: [[Warfarin (Coumadin)]]
 
−
*Herpes zoster prophylaxis highly recommended
 
−
'''21-day cycle for 8 cycles, then 42-day cycle for 4 cycles (1 year)'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented at the 37th Annual Meeting of the European Group for Blood and Marrow Transplantation, Paris, France, April, 3-6, 2011. -->
 
−
# '''MMVAR/IFM 2005-04:''' Garderet L, Iacobelli S, Moreau P, Dib M, Lafon I, Niederwieser D, Masszi T, Fontan J, Michallet M, Gratwohl A, Milone G, Doyen C, Pegourie B, Hajek R, Casassus P, Kolb B, Chaleteix C, Hertenstein B, Onida F, Ludwig H, Ketterer N, Koenecke C, van Os M, Mohty M, Cakana A, Gorin NC, de Witte T, Harousseau JL, Morris C, Gahrton G. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 randomized phase III trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2012 Jul 10;30(20):2475-82. Epub 2012 May 14. Erratum in: J Clin Oncol. 2012 Sep 20;30(27):3429. [https://doi.org/10.1200/jco.2011.37.4918 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22585692 PubMed] NCT00256776
 
−
==ZRd {{#subobject:4e6061|Regimen=1}}==
 
−
ZRd: '''<u>Z</u>'''olinza (Vorinostat), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0c164a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.14429 Sanchez et al. 2016 (PRO-2580)]
 
−
|2012-2014
 
−
|style="background-color:#91cf61"|Phase 2b
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Vorinostat (Zolinza)]] 400 mg PO once per day on days 1 to 7, 15 to 21
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''PRO-2580:''' Sanchez L, Vesole DH, Richter JR, Biran N, Bilotti E, McBride L, Anand P, Ivanovski K, Siegel DS. A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide-containing regimens. Br J Haematol. 2017 Feb;176(3):440-447. Epub 2016 Nov 18. [https://doi.org/10.1111/bjh.14429 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27859001 PubMed] NCT01502085
 
−
=Relapsed or refractory, other combinations=
 
−
==Bortezomib, Thalidomide, Dexamethasone, Panobinostat {{#subobject:6c61d0|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1bf613|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S2352-3026(16)30165-X Popat et al. 2016 (MUK-six)]
 
−
|2013-2014
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|-
 
−
|}
 
−
''Note: this is the dose used in the phase 2 portion of the trial.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> SC once per day on days 1 & 8
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day
 
−
*[[Panobinostat (Farydak)]] 20 mg PO once per day on days 1, 3, 5, 8, 10, 12
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 8, 9
 
−
'''21-day cycle for 16 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MUK-six:''' Popat R, Brown SR, Flanagan L, Hall A, Gregory W, Kishore B, Streetly M, Oakervee H, Yong K, Cook G, Low E, Cavenagh J; Myeloma UK Early Phase Clinical Trial Network.. Bortezomib, thalidomide, dexamethasone, and panobinostat for patients with relapsed multiple myeloma (MUK-six): a multicentre, open-label, phase 1/2 trial. Lancet Haematol. 2016 Dec;3(12):e572-e580. [https://doi.org/10.1016/S2352-3026(16)30165-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27843120 PubMed] NCT02145715
 
−
==DCEP {{#subobject:6dd02a|Regimen=1}}==
 
−
DCEP: '''<u>D</u>'''examethasone, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:bba45e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1038/sj.bmt.1703240 Lazzarino et al. 2001]
 
−
|2000-2001
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: this protocol is reported as a mobilization regimen prior to high dose autologous transplant; all patients had received prior therapy.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 1600 mg/m<sup>2</sup>)
 
−
*[[Etoposide (Vepesid)]] 40 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 160 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 40 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting 48 hours after chemotherapy and continuing through stem cell collection
 
−
'''One course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:3b5550|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/17436400 Dadacaridou et al. 2007]
 
−
|NR in abstract
 
−
|style="background-color:#ffffbe"|Phase 2, <20 patients reported
 
−
|-
 
−
|}
 
−
''Note: These limited details are based on the abstract's description only. Full article was not available for review.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg IV bolus once per day on days 1 to 4
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1600 mg/m<sup>2</sup>)
 
−
*[[Etoposide (Vepesid)]] 40 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 160 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] 15 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 60 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen) | G-CSF]] SC once per day, starting on day 5, to continue until neutrophil recovery
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Lazzarino M, Corso A, Barbarano L, Alessandrino EP, Cairoli R, Pinotti G, Ucci G, Uziel L, Rodeghiero F, Fava S, Ferrari D, Fiumanò M, Frigerio G, Isa L, Luraschi A, Montanara S, Morandi S, Perego D, Santagostino A, Savarè M, Vismara A, Morra E. DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an effective regimen for peripheral blood stem cell collection in multiple myeloma. Bone Marrow Transplant. 2001 Nov;28(9):835-9. [https://doi.org/10.1038/sj.bmt.1703240 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11781643 PubMed]
 
−
# Dadacaridou M, Papanicolaou X, Maltesas D, Megalakaki C, Patos P, Panteli K, Repousis P, Mitsouli-Mentzikof C. Dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) for relapsed or refractory multiple myeloma patients. J BUON. 2007 Jan-Mar;12(1):41 to 4. [https://pubmed.ncbi.nlm.nih.gov/17436400 PubMed]
 
−
 
−
==DTPACE {{#subobject:e5c635|Regimen=1}}==
 
−
DTPACE: '''<u>D</u>'''examethasone, '''<u>T</u>'''halidomide, '''<u>P</u>'''latinol (Cisplatin), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:02d8a9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.01.055 Lee et al. 2003 (UARK-98035)]
 
−
|1998-2001
 
−
|style="background-color:#91cf61"|Prospective
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Thalidomide (Thalomid)]] 400 mg PO once per day, at night
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1600 mg/m<sup>2</sup>)
 
−
*[[Etoposide (Vepesid)]] 40 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 160 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day from day 5 until ANC greater than 1000/ul for two consecutive days
 
−
*[[Levofloxacin (Levaquin)]] 250 mg PO once per day from day 1 until ANC greater than 1000/ul for two consecutive days
 
−
*[[Fluconazole (Diflucan)]] 200 mg PO once per day from day 1 until ANC greater than 1000/ul for two consecutive days
 
−
*[[Acyclovir (Zovirax)]] 400 mg PO twice per day from day 1 until ANC greater than 1000/ul for two consecutive days
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 800/160 mg PO twice per day twice per week
 
−
'''4- to 6-week cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''UARK-98035:''' Lee CK, Barlogie B, Munshi N, Zangari M, Fassas A, Jacobson J, van Rhee F, Cottler-Fox M, Muwalla F, Tricot G. DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma. J Clin Oncol. 2003 Jul 15;21(14):2732-9. Erratum in: J Clin Oncol. 2008 Apr 20;26(12): 2066. [https://doi.org/10.1200/jco.2003.01.055 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12860952 PubMed]
 
−
==Hyper-CVAD {{#subobject:0df285|Regimen=1}}==
 
−
Hyper-CVAD: '''<u>Hyper</u>'''fractionated '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:62dcd6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1002/(SICI)1096-8652(199606)52:2%3C77::AID-AJH2%3E3.0.CO;2-2 Dimopoulos et al. 1996]
 
−
|NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 3 (total dose per cycle: 1800 mg/m<sup>2</sup>)
 
−
*[[Vincristine (Oncovin)]] 1 mg/day IV continuous infusion over 48 hours, started on day 4, '''12 hours after last dose of cyclophosphamide''', then 2 mg IV once on day 11
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours, started on day 4, '''12 hours after last dose of cyclophosphamide''' (total dose per cycle: 50 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup> PO once per day on days 1 to 5, 11 to 14
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 1800 mg/m<sup>2</sup>)
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day from day 6 until WBC count greater than 2000/uL for 2 consecutive days
 
−
*[[Ciprofloxacin (Cipro)]] 500 mg PO twice per day on days 8 to 18
 
−
*[[Fluconazole (Diflucan)]] 100 mg PO once per day on days 8 to 18
 
−
*[[Acyclovir (Zovirax)]] 200 mg PO three times per day on days 8 to 18
 
−
'''Up to 2 cycles (length not specified)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responding patients: [[#Cyclophosphamide_.26_Dexamethasone_2|Cyclophosphamide & Dexamethasone]] maintenance
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, modified {{#subobject:2fd9df|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.clml.2017.10.008 Saraceni et al. 2018]
 
−
|style="background-color:#ffffbe"|Retrospective
 
−
|-
 
−
|}
 
−
''Note: vincristine is a flat dose.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose per cycle: 2400 mg/m<sup>2</sup>)
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg)
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 5 or 6
 
−
*[[Mesna (Mesnex)]] 350 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1400 mg/m<sup>2</sup>)
 
−
*Antiviral prophylaxis with [[Valacyclovir (Valtrex)]] daily (dose not specified)
 
−
*"Most patients also received antifungal, antibacterial, and Pneumocysitc jiroveci pneumonia prophylaxis"
 
−
'''Duration of each cycle not specified; for most patients, treatment cycles were administered every 4 weeks'''
 
−
</div></div>
 
−
===References===
 
−
# Dimopoulos MA, Weber D, Kantarjian H, Delasalle KB, Alexanian R. HyperCVAD for VAD-resistant multiple myeloma. Am J Hematol. 1996 Jun;52(2):77-81. [https://doi.org/10.1002/(SICI)1096-8652(199606)52:2%3C77::AID-AJH2%3E3.0.CO;2-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8638645 PubMed]
 
−
# '''Retrospective:''' Saraceni MM, Scott E, Maziarz RT, Siegel MB, Bassale S, Jiing S, Medvedova E. Modified hyperCVAD versus bortezomib-hyperCAD in patients with relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2018 Jan;18(1):e77-e84. [https://doi.org/10.1016/j.clml.2017.10.008 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29169873 PubMed]
 
−
==KD-PACE {{#subobject:yg72na|Regimen=1}}==
 
−
KD-PACE: '''<u>K</u>'''yprolis (Carfilzomib), '''<u>D</u>'''examethasone, '''<u>P</u>'''latinol (Cisplatin), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide (Toposar)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:uldbe92|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.clml.2021.03.013 Alsouqi et al. 2021]
 
−
|style="background-color:#ffffbe"|Retrospective
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]]
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Etoposide (Vepesid)]]
 
−
</div></div>
 
−
===References===
 
−
#'''Retrospective:''' Alsouqi A, Khan M, Dhakal B, Du L, Harrell S, Hari P, Cornell RF. KD-PACE Salvage Therapy for Aggressive Relapsed Refractory Multiple Myeloma, Plasma Cell Leukemia and Extramedullary Myeloma. Clin Lymphoma Myeloma Leuk. 2021 Aug;21(8):526-535. Epub 2021 Apr 6. [https://doi.org/10.1016/j.clml.2021.03.013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33985931/ PubMed]
 
−
==KRD-PACE {{#subobject:0072na|Regimen=1}}==
 
−
KRD-PACE: '''<u>K</u>'''yprolis (Carfilzomib), '''<u>R</u>'''evlimid (Lenalidomide), '''<u>D</u>'''examethasone, '''<u>P</u>'''latinol (Cisplatin), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:0ndbe92|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.clml.2020.04.002 Cowan et al. 2020]
 
−
|style="background-color:#ffffbe"|Retrospective
 
−
|-
 
−
|}
 
−
''Note: PACE was administered as a continuous infusion.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9
 
−
*[[Lenalidomide (Revlimid)]] 10 to 25 mg PO once per day on days 1 to 4
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1600 mg/m<sup>2</sup>)
 
−
*[[Etoposide (Vepesid)]] 40 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 160 mg/m<sup>2</sup>)
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, modified {{#subobject:bdjd89|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.clml.2020.04.002 Cowan et al. 2020]
 
−
|style="background-color:#ffffbe"|Retrospective
 
−
|-
 
−
|}
 
−
''Note: PACE was administered as a continuous infusion.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 5, 6
 
−
*[[Lenalidomide (Revlimid)]] 10 to 25 mg PO once per day on days 5 to 8
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 5 to 8
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 5 (total dose per cycle: 40 mg/m<sup>2</sup>)
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 5 (total dose per cycle: 40 mg/m<sup>2</sup>)
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 5 (total dose per cycle: 1600 mg/m<sup>2</sup>)
 
−
*[[Etoposide (Vepesid)]] 40 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 5 (total dose per cycle: 160 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 10 mcg/kg per day S.C. was begun on day 10. Note that this regimen was used to mobilize autologous peripheral blood stem cells in the context of this manuscript.
 
−
*Antiviral prophylaxis with [[Valacyclovir (Valtrex)]] daily (dose not specified)
 
−
*"Most patients also received antifungal, antibacterial, and Pneumocysitc jiroveci pneumonia prophylaxis"
 
−
*All patients received anticoagulation therapy; individuals not receiving systemic therapeutic anticoagulation for another reason received enoxaparin 40 mg per day subcutaneously for DVT prophylaxis during chemotherapy
 
−
'''Duration of each cycle not specified; for most patients, treatment cycles were administered every 4 weeks'''
 
−
</div></div>
 
−
===References===
 
−
# '''Retrospective:''' Cowan AJ, Green DJ, Karami M, Becker PS, Tuazon S, Coffey DG, Hyun TS, Libby EN, Gopal AK, Holmberg LA. KRD-PACE Mobilization for Multiple Myeloma Patients With Significant Residual Disease Before Autologous Stem-Cell Transplantation. Clin Lymphoma Myeloma Leuk. 2020 Sep;20(9):602-609. [https://doi.org/10.1016/j.clml.2020.04.002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32457024 PubMed]
 
−
==V-HyperCAD {{#subobject:00a88b|Regimen=1}}==
 
−
V-HyperCAD: '''<u>V</u>'''elcade (Bortezomib), '''<u>Hyper</u>'''fractionated '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:48e7e9|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.clml.2017.10.008 Saraceni et al. 2018]
 
−
|style="background-color:#ffffbe"|Retrospective
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> SC once per day on days 1 & 4
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose per cycle: 2400 mg/m<sup>2</sup>)
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 5 or 6
 
−
*[[Mesna (Mesnex)]] 350 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1
 
−
*Antiviral prophylaxis with [[Acyclovir (Zovirax)]] daily (dose not specified)
 
−
*"Most patients also received antifungal, antibacterial, and Pneumocysitc jiroveci pneumonia prophylaxis"
 
−
'''Duration of each cycle not specified; for most patients, treatment cycles were administered every 4 weeks'''
 
−
</div></div>
 
−
===References===
 
−
# '''Retrospective:''' Saraceni MM, Scott E, Maziarz RT, Siegel MB, Bassale S, Jiing S, Medvedova E. Modified hyperCVAD versus bortezomib-hyperCAD in patients with relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2018 Jan;18(1):e77-e84. [https://doi.org/10.1016/j.clml.2017.10.008 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29169873 PubMed]
 
−
==VMPT {{#subobject:c7cda5|Regimen=1}}==
 
−
VMPT: '''<u>V</u>'''elcade (Bortezomib), '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone, '''<u>T</u>'''halidomide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d55f41|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/109/7/2767.full Palumbo et al. 2007]
 
−
|2004-2005
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|-
 
−
|}
 
−
''Note: This is the MTD dosing of this phase 1/2 trial.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 15, 22
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 35
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 6 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''35-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Palumbo A, Ambrosini MT, Benevolo G, Pregno P, Pescosta N, Callea V, Cangialosi C, Caravita T, Morabito F, Musto P, Bringhen S, Falco P, Avonto I, Cavallo F, Boccadoro M; Italian Multiple Myeloma Network; Gruppo Italiano Malattie Ematologicche dell'Adulto. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. Blood. 2007 Apr 1;109(7):2767-72. [http://www.bloodjournal.org/content/109/7/2767.full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17148584 PubMed]
 
−
<section end=rrmm />
 
−
<section begin=rrmm-consol />
 
−
=Consolidation after second-line therapy=
 
−
==Bortezomib monotherapy {{#subobject:bb5567|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ba71b2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa043445 Richardson et al. 2005 (APEX)]
 
−
|2002-2003
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
 
−
|[[Multiple_myeloma_-_historical#Dexamethasone_monotherapy_3|High-dose dexamethasone]]
 
−
|style="background-color:#91cf60"|Seems to have superior OS<sup>1</sup><br>(HR 0.77)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for APEX is based on the 2007 update.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Multiple_myeloma_-_historical#Bortezomib_monotherapy|Bortezomib]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*[[:Category:Bisphosphonates|Bisphosphonate]] IV therapy once every 3 to 4 weeks unless contraindicated
 
−
'''35-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''APEX:''' Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Bladé J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC; Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005 Jun 16;352(24):2487-98. [https://doi.org/10.1056/NEJMoa043445 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15958804 PubMed] NCT00048230
 
−
## '''Pooled subgroup analysis:''' Jagannath S, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Cowan JM, Anderson KC. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia. 2007 Jan;21(1):151-7. Epub 2006 Nov 9. [https://www.nature.com/articles/2404442 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17096017 PubMed]
 
−
## '''Update:''' Richardson PG, Sonneveld P, Schuster M, Irwin D, Stadtmauer E, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San Miguel J, Bladé J, Boccadoro M, Cavenagh J, Alsina M, Rajkumar SV, Lacy M, Jakubowiak A, Dalton W, Boral A, Esseltine DL, Schenkein D, Anderson KC. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood. 2007 Nov 15;110(10):3557-60. Epub 2007 Aug 9. [http://www.bloodjournal.org/content/110/10/3557.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17690257 PubMed]
 
−
==Melphalan, then auto HSCT {{#subobject:149d91|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:83243a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70245-1 Cook et al. 2014 (NCRI Myeloma X Relapse)]
 
−
|2008-2012
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[#Cyclophosphamide_monotherapy_88|Cyclophosphamide]]
 
−
|style="background-color:#91cf60"|Seems to have superior OS<sup>1</sup> <br>(HR 0.56, 95% CI 0.35-0.90)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2016 update.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#PAD|PAD]] x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m<sup>2</sup> IV once on day -2
 
−
'''Stem cells re-infused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
# '''NCRI Myeloma X Relapse:''' Cook G, Williams C, Brown JM, Cairns DA, Cavenagh J, Snowden JA, Ashcroft AJ, Fletcher M, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Chalmers A, O'Connor S, Drayson MT, Morris TC; National Cancer Research Institute Haemato-oncology Clinical Studies Group. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Jul;15(8):874-85. Epub 2014 Jun 16. Erratum in: Lancet Oncol. 2014 Aug;15(9):e365. Dosage error in article text. [https://doi.org/10.1016/S1470-2045(14)70245-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24948586 PubMed] NCT00747877
 
−
## '''Update:''' Cook G, Ashcroft AJ, Cairns DA, Williams CD, Brown JM, Cavenagh JD, Snowden JA, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Pratt G, Chown S, Heartin E, O'Connor S, Drayson MT, Hockaday A, Morris TC; National Cancer Research Institute Haemato-oncology Clinical Studies Group. The effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Lancet Haematol. 2016 Jul;3(7):e340-51. [https://doi.org/10.1016/S2352-3026(16)30049-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27374467 PubMed]
 
−
## '''Subgroup analysis:''' Cook G, Royle KL, O'Connor S, Cairns DA, Ashcroft AJ, Williams CD, Hockaday A, Cavenagh JD, Snowden JA, Ademokun D, Tholouli E, Andrews VE, Jenner M, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Pratt G, Drayson MT, Brown JM, Morris TCM; National Cancer Research Institute Haemato-oncology Clinical Studies Group. The impact of cytogenetics on duration of response and overall survival in patients with relapsed multiple myeloma (long-term follow-up results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Br J Haematol. 2019 May;185(3):450-467. Epub 2019 Feb 6. [https://doi.org/10.1111/bjh.15782 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519200/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30729512 PubMed]
 
−
=Maintenance after second-line therapy=
 
−
==Bortezomib & Cyclophosphamide {{#subobject:eaadfe|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5e9a21|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13653 de Waal et al. 2015]
 
−
|2009-2013
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#VDC|VDC]] x 6
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV or SC once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day
 
−
====Supportive therapy====
 
−
*Pneumococccal and anti-fungal prophylaxis "according to local protocols"
 
−
*[[Valacyclovir (Valtrex)]] (dose not specified) for herpes prophylaxis
 
−
'''14-day cycle for up to 26 cycles (1 year)'''
 
−
</div></div>
 
−
===References===
 
−
# de Waal EG, de Munck L, Hoogendoorn M, Woolthuis G, van der Velden A, Tromp Y, Vellenga E, Hovenga S. Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients. Br J Haematol. 2015 Dec;171(5):720-5. Epub 2015 Sep 11. [https://doi.org/10.1111/bjh.13653 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26358087 PubMed]
 
−
==KPD {{#subobject:bfa533|Regimen=1}}==
 
−
KPD: '''<u>K</u>'''yprolis (Carfilzomib), '''<u>P</u>'''omalidomide, '''<u>D</u>'''examethasone
 
−
<br>CPD: '''<u>C</u>'''arfilzomib, '''<u>P</u>'''omalidomide, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:edd05b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643003/ Shah et al. 2015 (PO-MM-PI-0034)]
 
−
|2011-NR
 
−
|style="background-color:#91cf61"|Phase 1
 
−
|-
 
−
|}
 
−
''Note, although this is described as a Phase 1 trial, an additional 20 patients were enrolled at the MTD, which is the dose reported here.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#KPD|KPD]] x 6
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Carfilzomib (Kyprolis)]] 27 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 15, 16
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*"[[:Category:Antivirals|Anti-viral therapy]]"
 
−
*[[Aspirin]] 81 mg PO once per day
 
−
**[[:Category:Low molecular weight heparins|Low molecular weight heparin]] was used in patients intolerant of aspirin
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Jatin J. Shah, MD, Edward A. Stadtmauer, MD, Rafat Abonour, MD, Adam D. Cohen, MD, William I. Bensinger, MD, Cristina Gasparetto, MD, Jonathan L. Kaufman, MD, Suzanne Lentzsch, MD, Dan T. Vogl, MD, Robert Z. Orlowski, MD, PhD, Erica L. Kim, MPH, Marti McKinley, BSN, MBA, Brian G.M. Durie, MD. A Multi-Center Phase I/II Trial of Carfilzomib and Pomalidomide with Dexamethasone (Car-Pom-d) in Patients with Relapsed/Refractory Multiple Myeloma. 2013 ASH Annual Meeting abstract 690. [http://www.myelomabeacon.com/resources/mtgs/ash2013/abs/690/ link to abstract] [http://myeloma.org/pdfs/Shah-74-3909.pdf link to presentation] '''contains dosing details in manuscript''' -->
 
−
# '''PO-MM-PI-0034:''' Shah JJ, Stadtmauer EA, Abonour R, Cohen AD, Bensinger WI, Gasparetto C, Kaufman JL, Lentzsch S, Vogl DT, Gomes CL, Pascucci N, Smith DD, Orlowski RZ, Durie BG. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015 Nov 12;126(20):2284-90. Epub 2015 Sep 17. [http://www.bloodjournal.org/content/126/20/2284.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643003/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26384354 PubMed] NCT01464034
 
−
==Pomalidomide monotherapy {{#subobject:5d4f4d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a3138c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/130/10/1198.long Paludo et al. 2017 (MC1082)]
 
−
|2012-2014
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|ORR: 86%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#PVD|PVD]] x 8
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 325 mg PO once per day
 
−
**Full dose anticoagulation with [[:Category:Low molecular weight heparins|LMWH]] or [[Warfarin (Coumadin)]] could be substituted at physician discretion
 
−
*[[Acyclovir (Zovirax)]] or equivalent for VZV prophylaxis
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MC1082:''' Paludo J, Mikhael JR, LaPlant BR, Halvorson AE, Kumar S, Gertz MA, Hayman SR, Buadi FK, Dispenzieri A, Lust JA, Kapoor P, Leung N, Russell SJ, Dingli D, Go RS, Lin Y, Gonsalves WI, Fonseca R, Bergsagel PL, Roy V, Sher T, Chanan-Khan AA, Ailawadhi S, Stewart AK, Reeder CB, Richardson PG, Rajkumar SV, Lacy MQ. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma. Blood. 2017 Sep 7;130(10):1198-1204. Epub 2017 Jul 6. [http://www.bloodjournal.org/content/130/10/1198.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606008/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28684537 PubMed] NCT01212952
 
−
==Pomalidomide & Prednisone {{#subobject:519843|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:171099|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/122/16/2799.full Larocca et al. 2013 (PO0023)]
 
−
|2010-2012
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|ORR: 51%
 
−
|-
 
−
|}
 
−
''Details are for the phase 2 portion of the published phase 1/2 trial.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#PCP|PCP]] x 6
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]] 1 mg PO once per day
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 25 mg PO once every other day
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 100 mg PO once per day or [[:Category:Low_molecular_weight_heparins|low-molecular-weight heparin]] "according to patient risk"
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''PO0023:''' Larocca A, Montefusco V, Bringhen S, Rossi D, Crippa C, Mina R, Galli M, Marcatti M, La Verde G, Giuliani N, Magarotto V, Guglielmelli T, Rota-Scalabrini D, Omedé P, Santagostino A, Baldi I, Carella AM, Boccadoro M, Corradini P, Palumbo A. Pomalidomide, cyclophosphamide and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open label study. Blood. 2013 Oct 17;122(16):2799-806. Epub 2013 Aug 16. [http://www.bloodjournal.org/content/122/16/2799.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23954889 PubMed] NCT01166113
 
−
==RVD {{#subobject:fe8a85|Regimen=1}}==
 
−
RVD: '''<u>R</u>'''evlimid (Lenalidomide), '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone
 
−
<br>VDR: '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone, '''<u>R</u>'''evlimid (Lenalidomide)
 
−
<br>VRD: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), '''<u>D</u>'''examethasone
 
−
<br>VRd: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0c163e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123434/ Richardson et al. 2014 (DFCI 06-147)]
 
−
|2006-2008
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#RVD|RVD]] salvage
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] (at previously tolerated dose) PO once per day on days 1 to 14
 
−
*[[Bortezomib (Velcade)]] (at previously tolerated dose) IV once per day on days 1 & 8
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 10 mg PO once per day on days 1, 2, 8, 9
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 81 mg or 325 mg PO once per day
 
−
*[[:Category:Antivirals|Antiviral]] therapy for VZV prophylaxis
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''DFCI 06-147:''' Richardson PG, Xie W, Jagannath S, Jakubowiak A, Lonial S, Raje NS, Alsina M, Ghobrial IM, Schlossman RL, Munshi NC, Mazumder A, Vesole DH, Kaufman JL, Colson K, McKenney M, Lunde LE, Feather J, Maglio ME, Warren D, Francis D, Hideshima T, Knight R, Esseltine DL, Mitsiades CS, Weller E, Anderson KC. A phase II trial of lenalidomide, bortezomib and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood. 2014 Mar 6;123(10):1461-9. Epub 2014 Jan 15. [http://www.bloodjournal.org/content/123/10/1461.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123434/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24429336 PubMed] NCT00378209
 
−
<section end=rrmm-consol />
 
−
{{#lst:Multiple myeloma|bottom}}
 
−
[[Category:Multiple myeloma regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Plasma cell dyscrasias]]
 

Latest revision as of 00:13, 18 June 2023

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