Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
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</div>
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{{#lst:Section editor transclusions|tcl}}
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{{#lst:Section editor transclusions|anhl}}
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
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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>
+
|<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>
+
<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>
 
|}
 
|}
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
−
''Note: a variant of this disease, aggressive NK-cell leukemia, is usually considered a separate entity (somewhat analogous to [[plasma cell leukemia]] and [[multiple myeloma]]). There are no prospective trials reported for this variant.''
+
''Transformed lymphoma, often referred to as Richter's transformation, most commonly arises from a preceding indolent lymphoma - usually [[Follicular lymphoma|follicular lymphoma]] or [[Chronic lymphocytic leukemia|chronic lymphocytic leukemia]]. It is typically treated as per the histologic subtype, which is usually [[Diffuse large B-cell lymphoma|DLBCL]]. However, some regimens specific to transformed lymphoma have been developed and are included here.''
−
=Guidelines=
+
=All lines of therapy=
−
==[http://www.esmo.org/ ESMO]==
+
==Axicabtagene ciloleucel monotherapy {{#subobject:78231d|Regimen=1}}==
−
*'''2015:''' d'Amore et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Peripheral-T-Cell-Lymphomas Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
=="How I Treat"==
 
−
*'''2013:''' Tse E, Kwong YL. How I treat NK/T-cell lymphomas. Blood. 2013 Jun 20;121(25):4997-5005. Epub 2013 May 7. [http://www.bloodjournal.org/content/121/25/4997.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/23652805 PubMed]
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf NCCN Guidelines - T-cell Lymphomas]
 
−
=Untreated=
 
−
==DDGP {{#subobject:abc3fd|Regimen=1}}==
 
−
DDGP: '''<u>D</u>'''examethasone, '''<u>D</u>'''DP (Cisplatin), '''<u>G</u>'''emcitabine, '''<u>P</u>'''egaspargase
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:d2e0fd|Variant=1}}===
+
===Regimen {{#subobject:e3e516|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| 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/PMC5363293/ Locke et al. 2017 (ZUMA-1)]
 +
|2015-2016
 +
|style="background-color:#ffffbe"|Phase 1/2, <20 pts in subgroup (RT)
 +
| style="background-color:#e0ecf4" |ORR: 82%
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Lymphodepletion with [[Autologous_HSCT#FC|FC]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Axicabtagene ciloleucel (Yescarta)]] target dose of 2 × 10<sup>6</sup> CAR T cells/kg IV once on day 0
 +
====Supportive therapy====
 +
*[[Acetaminophen (Tylenol)]] 650 mg PO once on day 0, approximately 60 minutes prior to [[Axicabtagene ciloleucel (Yescarta)]]
 +
*[[Diphenhydramine (Benadryl)]] 12.5 mg IV or PO once on day 0, approximately 60 minutes prior to [[Axicabtagene ciloleucel (Yescarta)]]
 +
 +
'''One course; patients with initial response and disease progression at least 3 months later could be retreated'''
 +
</div></div>
 +
===References===
 +
#'''ZUMA-1:''' Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. [https://doi.org/10.1016/j.ymthe.2016.10.020 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28129122 PubMed] NCT02348216
 +
##'''Update:''' Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. [https://doi.org/10.1056/NEJMoa1707447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29226797 PubMed]
 +
##'''Update:''' Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. [https://doi.org/10.1016/S1470-2045(18)30864-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733402/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30518502 PubMed]
 +
==Bendamustine monotherapy {{#subobject:40b6d7|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:2806ae|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/10.1200/jco.2007.12.5070 Friedberg et al. 2008]
 +
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
 +
'''21-day cycle for up to 12 cycles'''
 +
</div></div>
 +
===References===
 +
<!-- Presented in part at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, Florida -->
 +
# Friedberg JW, Cohen P, Chen L, Robinson KS, Forero-Torres A, La Casce AS, Fayad LE, Bessudo A, Camacho ES, Williams ME, van der Jagt RH, Oliver JW, Cheson BD. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol. 2008 Jan 10;26(2):204-10. Erratum in: J Clin Oncol. 2008 Apr 10;26(11) 1911. [https://doi.org/10.1200/jco.2007.12.5070 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18182663 PubMed]
 +
==<sup>131</sup>Iodine-Tositumomab monotherapy {{#subobject:4f79a4|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1c0cb9|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/10.1200/jco.2000.18.6.1316 Vose et al. 2000]
 +
|style="background-color:#91cf61"|Phase 2
 +
|-
 +
|}
 +
''Also evaluated in low-grade NHL but subtype was not specified. Now obsolete as this drug has been discontinued.''
 +
====Radioconjugate therapy, dosimetric step====
 +
*On Day 0, infusions of:
 +
**Tositumomab 450 mg IV over 1 hour
 +
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
 +
**First scan of whole body dosimetry & redistribution
 +
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 +
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 +
====Radioconjugate therapy, therapeutic step====
 +
*Any day from day 7-14, infusions of:
 +
**Tositumomab 450 mg IV over 1 hour
 +
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 +
***65 cGy total body dose used for patients with platelet counts of 100-150,000/mm3
 +
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 +
</div></div>
 +
===References===
 +
# Vose JM, Wahl RL, Saleh M, Rohatiner AZ, Knox SJ, Radford JA, Zelenetz AD, Tidmarsh GF, Stagg RJ, Kaminski MS. Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2000 Mar;18(6):1316-23. [https://doi.org/10.1200/jco.2000.18.6.1316 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10715303 PubMed]
 +
==Lenalidomide monotherapy {{#subobject:590ccf|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:87163f|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/10.1093/annonc/mdq626 Witzig et al. 2011 (NHL-003)]
 +
|style="background-color:#91cf61"|Phase 2
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
# '''NHL-003:''' Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, Bouabdallah R, Haioun C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL, Czuczman MS. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 2011 Jul;22(7):1622-7. Epub 2011 Jan 12. [https://doi.org/10.1093/annonc/mdq626 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21228334 PubMed] NCT00413036
 +
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:cce1e0|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:8347d9|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/10.1038/leu.2013.95 Wang et al. 2013 (MDACC 2005-0461)]
 +
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 +
*[[Rituximab (Rituxan)]] as follows:
 +
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
# '''MDACC 2005-0461:''' Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, Shah J, Thomas S, Younes A, Hosing C, Zhang L, Newberry KJ, Desai M, Cheng N, Badillo M, Bejarano M, Chen Y, Young KH, Champlin R, Kwak L, Fayad L. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013 Sep;27(9):1902-9. Epub 2013 Apr 2. [https://doi.org/10.1038/leu.2013.95 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23545991 PubMed] NCT00294632
 +
==Lenalidomide & Tafasitamab {{#subobject:d4abx3|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:737708|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(20)30225-4 Salles et al. 2020 (L-MIND)]
 +
|2016-2017
 +
| style="background-color:#91cf61" |Phase 2 (RT)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Lenalidomide (Revlimid)]] as follows:
 +
**Cycles 1 to 12: 25 mg PO once per day on days 1 to 21
 +
*[[Tafasitamab (Monjuvi)]] as follows:
 +
**Cycle 1: 12 mg/kg IV over 2 hours once per day on days 1, 4, 8, 15, 22
 +
**Cycles 2 & 3: 12 mg/kg IV over 2 hours once per day on days 1, 8, 15, 22
 +
**Cycle 4 onwards: 12 mg/kg IV over 2 hours once per day on days 1 & 15
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
<!-- # '''Abstract:''' Kami J. Maddocks, Eva González Barca, Wojciech Jurczak, Anna Marina Liberati, Johannes Duell, Zsolt Nagy, Tomáš Papajík, Marc Andre, Nagesh Kalakonda, Martin H. Dreyling, Pier Luigi Zinzani, Sumeet Vijay Ambarkhane, Johannes Weirather, and Gilles A. Salles. L-mind: MOR208 combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large b-cell lymphoma (R-R DLBCL)—A single-arm phase II study. Journal of Clinical Oncology 2017 35:15_suppl, 7514-7514 [https://doi.org/10.1200/JCO.2017.35.15_suppl.7514 link to abstract] -->
 +
# '''L-MIND:''' Salles G, Duell J, González Barca E, Tournilhac O, Jurczak W, Liberati AM, Nagy Z, Obr A, Gaidano G, André M, Kalakonda N, Dreyling M, Weirather J, Dirnberger-Hertweck M, Ambarkhane S, Fingerle-Rowson G, Maddocks K. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul;21(7):978-988. Epub 2020 Jun 5. [https://doi.org/10.1016/s1470-2045(20)30225-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32511983 PubMed] NCT02399085
 +
==Lisocabtagene maraleucel monotherapy {{#subobject:6e6u14|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:6nvha6|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(20)31366-0 Abramson et al. 2020 (TRANSCEND NHL-001)]
 +
|2016-2019
 +
| style="background-color:#91cf61" |Phase 1 (RT)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Lisocabtagene maraleucel (Breyanzi)]]
 +
</div></div>
 +
===References===
 +
#'''TRANSCEND NHL-001:''' Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. Epub 2020 Sep 1. [https://doi.org/10.1016/s0140-6736(20)31366-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32888407 PubMed] NCT02631044
 +
==Loncastuximab tesirine monotherapy {{#subobject:jgua99|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:jagix0|Variant=1}}===
 +
{| class="wikitable sortable" 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://doi.org/10.1016/s1470-2045(21)00139-x Caimi et al. 2021 (LOTIS-2)]
 +
|2018-2019
 +
| style="background-color:#91cf61" |Phase 2 (RT)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Antibody-drug conjugate therapy====
 +
*[[Loncastuximab tesirine (Zynlonta)]] as follows:
 +
**Cycles 1 & 2: 0.15 mg/kg IV over 30 minutes once on day 1
 +
**Cycle 3 onwards: 0.075 mg/kg IV over 30 minutes once on day 1
 +
====Supportive therapy====
 +
*[[Dexamethasone (Decadron)]] 4 mg IV or PO twice per day on days -1 to 2 (3 days total)
 +
'''21-day cycles for up to 18 cycles (1 year)'''
 +
</div></div>
 +
===References===
 +
#'''LOTIS-2:''' Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800. Epub 2021 May 11. [https://doi.org/10.1016/s1470-2045(21)00139-x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33989558/ PubMed] NCT03589469
 +
==OFAR {{#subobject:bd6061|Regimen=1}}==
 +
OFAR: '''<u>O</u>'''xaliplatin, '''<u>F</u>'''ludarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>R</u>'''ituximab
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:bd771f|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.2007.11.8513 Tsimberidou et al. 2008]
 +
|2004-2006
 +
|style="background-color:#91cf61"|Phase 2
 +
| style="background-color:#1a9850" |Likely has true ORR > 20%
 +
|-
 +
|}
 +
''Note: the manuscript does not specify what sequence the rituximab is given in.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Oxaliplatin (Eloxatin)]] 25 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 4, '''given first (see note)'''
 +
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 2 & 3, '''given second, within 30 minutes of completion of oxaliplatin (see note)'''
 +
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 & 3, '''given third, 4 hours after start of fludarabine (see note)'''
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] as follows (see note):
 +
**Cycle 1: 375 mg/m<sup>2</sup> IV over 4 to 6 hours once on day 3
 +
**Cycles 2 to 6: 375 mg/m<sup>2</sup> IV over 4 to 6 hours once on day 1
 +
====Supportive therapy====
 +
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6
 +
*Herpes zoster and PCP (Pneumocystis jiroveci pneumonia) prophylaxis used
 +
'''28-day cycle for up to 6 cycles'''
 +
</div></div>
 +
===References===
 +
# Tsimberidou AM, Wierda WG, Plunkett W, Kurzrock R, O'Brien S, Wen S, Ferrajoli A, Ravandi-Kashani F, Garcia-Manero G, Estrov Z, Kipps TJ, Brown JR, Fiorentino A, Lerner S, Kantarjian HM, Keating MJ. Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter's syndrome or fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2008 Jan 10;26(2):196-203. [https://doi.org/10.1200/jco.2007.11.8513 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18182662 PubMed]
 +
==Pembrolizumab monotherapy {{#subobject:1089ff|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:f10e64|Variant=1}}===
 +
{| class="wikitable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492091/ Ding et al. 2017 (MC1485)]
 +
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
 +
| style="background-color:#d9ef8b" |Unlikely to have true ORR > 20%
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
 +
'''21-day cycle for up to 35 cycles (2 years)'''
 +
</div></div>
 +
===References===
 +
# '''MC1485:''' Ding W, LaPlant BR, Call TG, Parikh SA, Leis JF, He R, Shanafelt TD, Sinha S, Le-Rademacher J, Feldman AL, Habermann TM, Witzig TE, Wiseman GA, Lin Y, Asmus E, Nowakowski GS, Conte MJ, Bowen DA, Aitken CN, Van Dyke DL, Greipp PT, Liu X, Wu X, Zhang H, Secreto CR, Tian S, Braggio E, Wellik LE, Micallef I, Viswanatha DS, Yan H, Chanan-Khan AA, Kay NE, Dong H, Ansell SM. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood. 2017 Jun 29;129(26):3419-3427. Epub 2017 Apr 19. [http://www.bloodjournal.org/content/129/26/3419.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492091/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28424162 PubMed]
 +
==R-DHAP {{#subobject:aacad1|Regimen=1}}==
 +
R-DHAP: '''<u>R</u>'''ituximab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin)
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:482776|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
Line 30: Line 270:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://clincancerres.aacrjournals.org/content/22/21/5223.long Li et al. 2016 (CTTNKTL-III/IV)]
+
|[https://doi.org/10.1200/jco.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
−
|2011-2014
+
|2003-2011
−
|style="background-color:#1a9851"|Phase 4 (E-switch-ic)
+
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#SMILE|SMILE]]
+
|[[#R-GDP|R-GDP]]
−
|style="background-color:#91cf60"|Seems to have superior OS<br>OS24: 74% vs 45%
+
|style="background-color:#d3d3d3"|Not reported
 
|-
 
|-
 
|}
 
|}
−
''Note: dosing information is from the [https://clinicaltrials.gov/show/NCT01501149 NCT record].''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Dexamethasone (Decadron)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 4
+
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
−
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
+
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
−
*[[Pegaspargase (Oncaspar)]] 2500 IU/m<sup>2</sup> IM once on day 1
+
'''21-day cycle for up to 3 cycles'''
−
'''21-day cycle for at least 3 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''CTTNKTL-III/IV:''' Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. [http://clincancerres.aacrjournals.org/content/22/21/5223.long link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/27060152 PubMed] NCT01501149
+
<!-- Presented in part at the Annual Meeting of the American Society of Hematology, Atlanta, GA, December 7-10, 2013, and the International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013. -->
−
==SMILE {{#subobject:db70b|Regimen=1}}==
+
# '''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740 PubMed] NCT00078949
−
SMILE: '''<u>S</u>'''teroid (Dexamethasone), '''<u>M</u>'''ethotrexate, '''<u>I</u>'''fosfamide, '''<u>L</u>'''-asparaginase, '''<u>E</u>'''toposide
+
## '''Subgroup Analysis:''' Kuruvilla J, MacDonald DA, Kouroukis CT, Cheung M, Olney HJ, Turner AR, Anglin P, Seftel M, Ismail WS, Luminari S, Couban S, Baetz T, Meyer RM, Hay AE, Shepherd L, Djurfeldt MS, Alamoudi S, Chen BE, Crump M. Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC-CTG LY12. Blood. 2015 Aug 6;126(6):733-8. Epub 2015 Jun 24. [http://www.bloodjournal.org/content/126/6/733.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26109202 PubMed]
 +
==R-EPOCH {{#subobject:86a128|Regimen=1}}==
 +
R-EPOCH: '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:9874b6|Variant=1}}===
+
===Regimen {{#subobject:51d707|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/10.1093/annonc/mdh093 Jermann et al. 2004]
 +
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
 +
|-
 +
|}
 +
''Note: this is not the dose-adjusted R-EPOCH regimen''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
====Chemotherapy====
 +
*[[Etoposide (Vepesid)]] 65 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 195 mg/m<sup>2</sup>)
 +
*[[Vincristine (Oncovin)]] 0.5 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 1.5 mg/m<sup>2</sup>)
 +
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 5
 +
*[[Doxorubicin (Adriamycin)]] 15 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 45 mg/m<sup>2</sup>)
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 14
 +
'''21-day cycle for 4 to 6 cycles'''
 +
</div></div>
 +
===References===
 +
# Jermann M, Jost LM, Taverna Ch, Jacky E, Honegger HP, Betticher DC, Egli F, Kroner T, Stahel RA. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol. 2004 Mar;15(3):511-6. [https://doi.org/10.1093/annonc/mdh093 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14998858 PubMed]
 +
==R-GDP {{#subobject:8624f9|Regimen=1}}==
 +
R-GDP: '''<u>R</u>'''ituximab, '''<u>G</u>'''emcitabine, '''<u>D</u>'''examethasone, '''<u>P</u>'''latinol (Cisplatin)
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:7e2222|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
Line 60: Line 329:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/120/15/2973.long Kwong et al. 2012]
+
|[https://doi.org/10.1200/jco.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
−
|2005-2012
+
|2003-2011
−
|style="background-color:#91cf61"|Phase 2
+
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
−
|style="background-color:#d3d3d3"|
+
|[[#R-DHAP|R-DHAP]]
−
|style="background-color:#d3d3d3"|
+
|style="background-color:#d3d3d3"|Not reported
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/22/21/5223.long Li et al. 2016 (CTTNKTL-III/IV)]
 
−
|2011-2014
 
−
|style="background-color:#1a9851"|Phase 4 (E-switch-ic)
 
−
|[[#DDGP|DDGP]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior OS
 
 
|-
 
|-
 
|}
 
|}
−
''Note: [[Asparaginase (Elspar)]] was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include [[Pegaspargase (Oncaspar)]] or [[Asparaginase Erwinia chrysanthemi (Erwinaze)]]. Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2011, describe 28-day cycles.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 2 to 4
+
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
−
====Chemotherapy====
+
'''21-day cycle for up to 3 cycles'''
−
*[[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV over 6 hours once on day 1
+
</div>
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with mesna'''
+
<div class="toccolours" style="background-color:#cbd5e7">
−
*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV over 2 hours once per day on days 8, 10, 12, 14, 16, 18, 20
+
====Subsequent treatment====
−
**Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli
+
*Responders: autologous HSCT
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 4
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 45 mg PO every 6 hours on days 2 to 4 (or until serum methotrexate level is below the toxic range), starting 24 hours after completion of [[Methotrexate (MTX)]]
 
−
**Methotrexate levels checked at 24, 48, and 72 hours after methotrexate is given, or until methotrexate levels fall below toxic range. Folinic acid should be continued until methotrexate levels are below toxic range.
 
−
*[[Mesna (Mesnex)]] 900 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with [[Ifosfamide (Ifex)]]'''
 
−
*Hydration with normal saline (no volume specified) every 8 hours on the day prior to [[Methotrexate (MTX)]]
 
−
*Patients told to drink at least 2 liters of fluid per day on days 1 to 4; target urine output of greater than or equal to 3 liters per day on days 1 to 4
 
−
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6, given until ANC greater than 1000/uL
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] or [[Pentamidine (Nebupent)]] for PJP prophylaxis
 
−
*[[Famotidine (Pepcid)]] and potassium slow release tablets (no dose specified) "for [[Dexamethasone (Decadron)]]" on days 2 to 4
 
−
*[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]]
 
−
*[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]]
 
−
'''28-day cycle for up to 6 cycles (see note)'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. [http://www.bloodjournal.org/content/120/15/2973.long link to original article] [http://www.bloodjournal.org/content/120/15/2973/suppl/DC1 supplemental materials] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/22919026 PubMed]
+
<!-- Presented in part at the Annual Meeting of the American Society of Hematology, Atlanta, GA, December 7-10, 2013, and the International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013. -->
−
# '''CTTNKTL-III/IV:''' Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. [http://clincancerres.aacrjournals.org/content/22/21/5223.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/27060152 PubMed] NCT01501149
+
# '''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740 PubMed] NCT00078949
−
=Relapsed or refractory=
+
## '''Subgroup Analysis:''' Kuruvilla J, MacDonald DA, Kouroukis CT, Cheung M, Olney HJ, Turner AR, Anglin P, Seftel M, Ismail WS, Luminari S, Couban S, Baetz T, Meyer RM, Hay AE, Shepherd L, Djurfeldt MS, Alamoudi S, Chen BE, Crump M. Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC-CTG LY12. Blood. 2015 Aug 6;126(6):733-8. Epub 2015 Jun 24. [http://www.bloodjournal.org/content/126/6/733.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26109202 PubMed]
−
==FluBuCy, then allo HSCT {{#subobject:84acb0|Regimen=1}}==
+
==Selinexor monotherapy {{#subobject:d68g71|Regimen=1}}==
−
FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:bfe434|Variant=1}}===
+
===Regimen {{#subobject:y42c19|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
Line 109: Line 366:
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)]
+
|[https://doi.org/10.1016/s2352-3026(20)30120-4 Kalakonda et al. 2020 (SADAL)]
−
|2004-2009
+
|2015-2019
−
| style="background-color:#91cf61" |Phase 2
+
| style="background-color:#91cf61" |Phase 2b (RT)
 
|-
 
|-
 
|}
 
|}
−
{{#lst:Allogeneic HSCT|bfe434}}
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Selinexor (Xpovio)]] 60 mg PO once per day on days 1 & 3
 +
'''7-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- # Glass B, rabbits Kamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N. High-dose chemotherapy Followed by allogeneic stem cell transplantation in relapsed and refractory high-risk aggressive non-Hodgkin's lymphoma: Results of a prospective study of the German high-grade non-Hodgkin's lymphoma study group. J Clin Oncol 30, 2012 (suppl; abstr 8004) -->
+
#'''SADAL:''' Kalakonda N, Maerevoet M, Cavallo F, Follows G, Goy A, Vermaat JSP, Casasnovas O, Hamad N, Zijlstra JM, Bakhshi S, Bouabdallah R, Choquet S, Gurion R, Hill B, Jaeger U, Sancho JM, Schuster M, Thieblemont C, De la Cruz F, Egyed M, Mishra S, Offner F, Vassilakopoulos TP, Warzocha K, McCarthy D, Ma X, Corona K, Saint-Martin JR, Chang H, Landesman Y, Joshi A, Wang H, Shah J, Shacham S, Kauffman M, Van Den Neste E, Canales MA. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020 Jul;7(7):e511-e522. [https://doi.org/10.1016/s2352-3026(20)30120-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32589977/ PubMed] NCT02227251
−
# '''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https://doi.org/10.1016/S1470-2045(14)70161-5 link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24827808 PubMed] NCT00785330
+
==Tisagenlecleucel monotherapy {{#subobject:d68f14|Regimen=1}}==
−
==Pembrolizumab monotherapy {{#subobject:84ac5y|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:ga3na4|Variant=1}}===
+
===Regimen {{#subobject:60fc19|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable" style="color:white; background-color:#404040"
−
!style="width: 25%"|Study
+
|<small>'''FDA-recommended dose'''</small>
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
|-
 +
|}
 +
{| class="wikitable" style="width: 60%; text-align:center;"  
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1182/blood-2016-12-756841 Kwong et al. 2017]
+
|[https://doi.org/10.1056/NEJMoa1804980 Schuster et al. 2018 (JULIET)]
−
| style="background-color:#ffffbe" |Case series
+
|style="background-color:#91cf61"|Phase 2
 +
| style="background-color:#9ebcda" |ORR: 59% (95% CI, 44-72)
 
|-
 
|-
 
|}
 
|}
−
''Note: prospective trials are underway.''
+
''The range given is the FDA-recommended dose.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Lymphodepleting therapy with [[Autologous_HSCT#FC|FC]] or [[Autologous_HSCT#Bendamustine_monotherapy|Bendamustine]]
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
−
*[[Pembrolizumab (Keytruda)]] 2 mg/kg IV once on day 1
+
*[[Tisagenlecleucel (Kymriah)]] 0.6 to 6 x 10<sup>8</sup> CTL019 transduced viable T-cells IV once on day 0
−
'''21-day cycles'''
+
'''One course'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
#Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, Khong PL, Loong F, Au-Yeung R, Iqbal J, Phipps C, Tse E. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017 Apr 27;129(17):2437-2442. Epub 2017 Feb 10. [https://doi.org/10.1182/blood-2016-12-756841 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28188133/ PubMed]
+
<!-- # '''Abstract:''' Schuster SJ, Bishop MR, Tam C, et al. Global Pivotal Phase 2 Trial of the CD19-Targeted Therapy CTL019 in Adult Patients with Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)—an Interim Analysis. Hematological Oncology. 2017;35(S2):27. [https://doi.org/full/10.1002/hon.2437_6 link to abstract] -->
−
==SMILE {{#subobject:db70b|Regimen=1}}==
+
# '''JULIET:''' Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1. [https://doi.org/10.1056/NEJMoa1804980 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30501490 PubMed] NCT02445248
−
SMILE: '''<u>S</u>'''teroid (Dexamethasone), '''<u>M</u>'''ethotrexate, '''<u>I</u>'''fosfamide, '''<u>L</u>'''-asparaginase, '''<u>E</u>'''toposide
+
##'''Update:''' Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1403-1415. Epub 2021 Sep 10. [https://doi.org/10.1016/s1470-2045(21)00375-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34516954/ PubMed]
 +
=Consolidation after salvage therapy=
 +
==BFR, then allo HSCT {{#subobject:c2659b|Regimen=1}}==
 +
BFR: '''<u>B</u>'''endamustine, '''<u>F</u>'''ludarabine, '''<u>R</u>'''ituximab
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:9874b6|Variant=1}}===
+
===Regimen {{#subobject:41fd04|Variant=1}}===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 33%"|Study
+
!style="width: 25%"|Study
−
!style="width: 33%"|Years of enrollment
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
 
|-
 
|-
−
|[https://doi.org/10.1111/j.1349-7006.2008.00768.x Yamaguchi et al. 2008]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260365/ Khouri et al. 2014 (MDACC 2008-0246)]
−
|2005-2006
+
| style="background-color:#ffffbe" |Phase 2, <20 pts in this subgroup
−
| style="background-color:#ffffbe" |Phase 1
 
−
|-
 
−
|[http://www.bloodjournal.org/content/120/15/2973.long Kwong et al. 2012]
 
−
|2005-2012
 
−
|style="background-color:#91cf61"|Phase 2
 
 
|-
 
|-
 
|}
 
|}
−
''Note: [[Asparaginase (Elspar)]] was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include [[Pegaspargase (Oncaspar)]] or [[Asparaginase Erwinia chrysanthemi (Erwinaze)]]. Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2008, describe 28-day cycles.''
+
{{#lst:Allogeneic HSCT|41fd04}}
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 2 to 4
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV over 6 hours once on day 1
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with mesna'''
 
−
*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV over 2 hours once per day on days 8, 10, 12, 14, 16, 18, 20
 
−
**Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 4
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 45 mg PO every 6 hours on days 2 to 4 (or until serum methotrexate level is below the toxic range), starting 24 hours after completion of [[Methotrexate (MTX)]]
 
−
**Methotrexate levels checked at 24, 48, and 72 hours after methotrexate is given, or until methotrexate levels fall below toxic range. Folinic acid should be continued until methotrexate levels are below toxic range.
 
−
*[[Mesna (Mesnex)]] 900 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with [[Ifosfamide (Ifex)]]'''
 
−
*Hydration with normal saline (no volume specified) every 8 hours on the day prior to [[Methotrexate (MTX)]]
 
−
*Patients told to drink at least 2 liters of fluid per day on days 1 to 4; target urine output of greater than or equal to 3 liters per day on days 1 to 4
 
−
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6, given until ANC greater than 1000/uL
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] or [[Pentamidine (Nebupent)]] for PJP prophylaxis
 
−
*[[Famotidine (Pepcid)]] and potassium slow release tablets (no dose specified) "for [[Dexamethasone (Decadron)]]" on days 2 to 4
 
−
*[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]]
 
−
*[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]]
 
−
'''28-day cycle for up to 6 cycles (see note)'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''Phase 1:''' Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, Suzumiya J, Okamura T, Nakamura S, Kawa K, Oshimi K. Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci. 2008 May;99(5):1016-20. Epub 2008 Feb 19. [https://doi.org/10.1111/j.1349-7006.2008.00768.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18294294 PubMed] content property of [http://hemonc.org HemOnc.org]
+
# '''MDACC 2008-0246:''' Khouri IF, Wei W, Korbling M, Turturro F, Ahmed S, Alousi A, Anderlini P, Ciurea S, Jabbour E, Oran B, Popat UR, Rondon G, Bassett RL Jr, Gulbis A. BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD. Blood. 2014 Oct 2;124(14):2306-12. Epub 2014 Aug 21. [http://www.bloodjournal.org/content/124/14/2306.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260365/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25145344 PubMed] NCT00880815
−
# Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. [http://www.bloodjournal.org/content/120/15/2973.long link to original article] [http://www.bloodjournal.org/content/120/15/2973/suppl/DC1 supplemental materials] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/22919026 PubMed]
+
[[Category:Transformed lymphoma regimens]]
−
[[Category:NK- and T-cell lymphoma regimens]]
 
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:T-cell lymphomas]]
+
[[Category:Aggressive lymphomas]]
 +
[[Category:Non-Hodgkin lymphomas]]

Revision as of 12:10, 29 October 2022

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Section editor transclusions

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Transformed lymphoma, often referred to as Richter's transformation, most commonly arises from a preceding indolent lymphoma - usually follicular lymphoma or chronic lymphocytic leukemia. It is typically treated as per the histologic subtype, which is usually DLBCL. However, some regimens specific to transformed lymphoma have been developed and are included here.

All lines of therapy

Axicabtagene ciloleucel monotherapy

Regimen

FDA-recommended dose
Study Years of enrollment Evidence Efficacy
Locke et al. 2017 (ZUMA-1) 2015-2016 Phase 1/2, <20 pts in subgroup (RT) ORR: 82%

Preceding treatment

  • Lymphodepletion with FC

Immunotherapy

Supportive therapy

One course; patients with initial response and disease progression at least 3 months later could be retreated

References

  1. ZUMA-1: Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. link to original article link to PMC article PubMed NCT02348216
    1. Update: Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. link to original article contains dosing details in manuscript link to PMC article PubMed
    2. Update: Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. link to original article link to PMC article contains dosing details in manuscript PubMed

Bendamustine monotherapy

Regimen

Study Evidence
Friedberg et al. 2008 Phase 2, <20 pts in this subgroup

Chemotherapy

21-day cycle for up to 12 cycles

References

  1. Friedberg JW, Cohen P, Chen L, Robinson KS, Forero-Torres A, La Casce AS, Fayad LE, Bessudo A, Camacho ES, Williams ME, van der Jagt RH, Oliver JW, Cheson BD. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol. 2008 Jan 10;26(2):204-10. Erratum in: J Clin Oncol. 2008 Apr 10;26(11) 1911. link to original article contains dosing details in manuscript PubMed

131Iodine-Tositumomab monotherapy

Regimen

Study Evidence
Vose et al. 2000 Phase 2

Also evaluated in low-grade NHL but subtype was not specified. Now obsolete as this drug has been discontinued.

Radioconjugate therapy, dosimetric step

  • On Day 0, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Radioconjugate therapy, therapeutic step

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

References

  1. Vose JM, Wahl RL, Saleh M, Rohatiner AZ, Knox SJ, Radford JA, Zelenetz AD, Tidmarsh GF, Stagg RJ, Kaminski MS. Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2000 Mar;18(6):1316-23. link to original article contains dosing details in manuscript PubMed

Lenalidomide monotherapy

Regimen

Study Evidence
Witzig et al. 2011 (NHL-003) Phase 2

Targeted therapy

28-day cycles

References

  1. NHL-003: Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, Bouabdallah R, Haioun C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL, Czuczman MS. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 2011 Jul;22(7):1622-7. Epub 2011 Jan 12. link to original article contains dosing details in manuscript PubMed NCT00413036

Lenalidomide & Rituximab (R2)

Regimen

Study Evidence
Wang et al. 2013 (MDACC 2005-0461) Phase 2, <20 pts in this subgroup

Targeted therapy

28-day cycles

References

  1. MDACC 2005-0461: Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, Shah J, Thomas S, Younes A, Hosing C, Zhang L, Newberry KJ, Desai M, Cheng N, Badillo M, Bejarano M, Chen Y, Young KH, Champlin R, Kwak L, Fayad L. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013 Sep;27(9):1902-9. Epub 2013 Apr 2. link to original article contains dosing details in manuscript PubMed NCT00294632

Lenalidomide & Tafasitamab

Regimen

Study Years of enrollment Evidence
Salles et al. 2020 (L-MIND) 2016-2017 Phase 2 (RT)

Targeted therapy

  • Lenalidomide (Revlimid) as follows:
    • Cycles 1 to 12: 25 mg PO once per day on days 1 to 21
  • Tafasitamab (Monjuvi) as follows:
    • Cycle 1: 12 mg/kg IV over 2 hours once per day on days 1, 4, 8, 15, 22
    • Cycles 2 & 3: 12 mg/kg IV over 2 hours once per day on days 1, 8, 15, 22
    • Cycle 4 onwards: 12 mg/kg IV over 2 hours once per day on days 1 & 15

28-day cycles

References

  1. L-MIND: Salles G, Duell J, González Barca E, Tournilhac O, Jurczak W, Liberati AM, Nagy Z, Obr A, Gaidano G, André M, Kalakonda N, Dreyling M, Weirather J, Dirnberger-Hertweck M, Ambarkhane S, Fingerle-Rowson G, Maddocks K. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul;21(7):978-988. Epub 2020 Jun 5. link to original article contains dosing details in manuscript PubMed NCT02399085

Lisocabtagene maraleucel monotherapy

Regimen

Study Years of enrollment Evidence
Abramson et al. 2020 (TRANSCEND NHL-001) 2016-2019 Phase 1 (RT)

Immunotherapy

References

  1. TRANSCEND NHL-001: Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. Epub 2020 Sep 1. link to original article PubMed NCT02631044

Loncastuximab tesirine monotherapy

Regimen

FDA-recommended dose
Study Years of enrollment Evidence
Caimi et al. 2021 (LOTIS-2) 2018-2019 Phase 2 (RT)

Antibody-drug conjugate therapy

  • Loncastuximab tesirine (Zynlonta) as follows:
    • Cycles 1 & 2: 0.15 mg/kg IV over 30 minutes once on day 1
    • Cycle 3 onwards: 0.075 mg/kg IV over 30 minutes once on day 1

Supportive therapy

21-day cycles for up to 18 cycles (1 year)

References

  1. LOTIS-2: Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800. Epub 2021 May 11. link to original article contains dosing details in abstract PubMed NCT03589469

OFAR

OFAR: Oxaliplatin, Fludarabine, Ara-C (Cytarabine), Rituximab

Regimen

Study Years of enrollment Evidence Efficacy
Tsimberidou et al. 2008 2004-2006 Phase 2 Likely has true ORR > 20%

Note: the manuscript does not specify what sequence the rituximab is given in.

Chemotherapy

  • Oxaliplatin (Eloxatin) 25 mg/m2 IV over 2 hours once per day on days 1 to 4, given first (see note)
  • Fludarabine (Fludara) 30 mg/m2 IV once per day on days 2 & 3, given second, within 30 minutes of completion of oxaliplatin (see note)
  • Cytarabine (Ara-C) 1000 mg/m2 IV over 2 hours once per day on days 2 & 3, given third, 4 hours after start of fludarabine (see note)

Targeted therapy

  • Rituximab (Rituxan) as follows (see note):
    • Cycle 1: 375 mg/m2 IV over 4 to 6 hours once on day 3
    • Cycles 2 to 6: 375 mg/m2 IV over 4 to 6 hours once on day 1

Supportive therapy

28-day cycle for up to 6 cycles

References

  1. Tsimberidou AM, Wierda WG, Plunkett W, Kurzrock R, O'Brien S, Wen S, Ferrajoli A, Ravandi-Kashani F, Garcia-Manero G, Estrov Z, Kipps TJ, Brown JR, Fiorentino A, Lerner S, Kantarjian HM, Keating MJ. Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter's syndrome or fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2008 Jan 10;26(2):196-203. link to original article contains dosing details in abstract PubMed

Pembrolizumab monotherapy

Regimen

Study Evidence Efficacy
Ding et al. 2017 (MC1485) Phase 2, <20 pts in this subgroup Unlikely to have true ORR > 20%

Immunotherapy

21-day cycle for up to 35 cycles (2 years)

References

  1. MC1485: Ding W, LaPlant BR, Call TG, Parikh SA, Leis JF, He R, Shanafelt TD, Sinha S, Le-Rademacher J, Feldman AL, Habermann TM, Witzig TE, Wiseman GA, Lin Y, Asmus E, Nowakowski GS, Conte MJ, Bowen DA, Aitken CN, Van Dyke DL, Greipp PT, Liu X, Wu X, Zhang H, Secreto CR, Tian S, Braggio E, Wellik LE, Micallef I, Viswanatha DS, Yan H, Chanan-Khan AA, Kay NE, Dong H, Ansell SM. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood. 2017 Jun 29;129(26):3419-3427. Epub 2017 Apr 19. link to original article contains dosing details in manuscript link to PMC article PubMed

R-DHAP

R-DHAP: Rituximab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Crump et al. 2014 (NCIC-CTG LY.12) 2003-2011 Phase 3 (C) R-GDP Not reported

Targeted therapy

Glucocorticoid therapy

Chemotherapy

  • Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m2)
  • Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours, started on day 1

21-day cycle for up to 3 cycles

References

  1. NCIC-CTG LY.12: Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains dosing details in manuscript PubMed NCT00078949
    1. Subgroup Analysis: Kuruvilla J, MacDonald DA, Kouroukis CT, Cheung M, Olney HJ, Turner AR, Anglin P, Seftel M, Ismail WS, Luminari S, Couban S, Baetz T, Meyer RM, Hay AE, Shepherd L, Djurfeldt MS, Alamoudi S, Chen BE, Crump M. Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC-CTG LY12. Blood. 2015 Aug 6;126(6):733-8. Epub 2015 Jun 24. link to original article contains dosing details in manuscript PubMed

R-EPOCH

R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Regimen

Study Evidence
Jermann et al. 2004 Phase 2, <20 pts in this subgroup

Note: this is not the dose-adjusted R-EPOCH regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

21-day cycle for 4 to 6 cycles

References

  1. Jermann M, Jost LM, Taverna Ch, Jacky E, Honegger HP, Betticher DC, Egli F, Kroner T, Stahel RA. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol. 2004 Mar;15(3):511-6. link to original article contains dosing details in manuscript PubMed

R-GDP

R-GDP: Rituximab, Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Crump et al. 2014 (NCIC-CTG LY.12) 2003-2011 Phase 3 (E-switch-ic) R-DHAP Not reported

Targeted therapy

Chemotherapy

Glucocorticoid therapy

21-day cycle for up to 3 cycles

Subsequent treatment

  • Responders: autologous HSCT

References

  1. NCIC-CTG LY.12: Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains dosing details in manuscript PubMed NCT00078949
    1. Subgroup Analysis: Kuruvilla J, MacDonald DA, Kouroukis CT, Cheung M, Olney HJ, Turner AR, Anglin P, Seftel M, Ismail WS, Luminari S, Couban S, Baetz T, Meyer RM, Hay AE, Shepherd L, Djurfeldt MS, Alamoudi S, Chen BE, Crump M. Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC-CTG LY12. Blood. 2015 Aug 6;126(6):733-8. Epub 2015 Jun 24. link to original article contains dosing details in manuscript PubMed

Selinexor monotherapy

Regimen

FDA-recommended dose
Study Years of enrollment Evidence
Kalakonda et al. 2020 (SADAL) 2015-2019 Phase 2b (RT)

Targeted therapy

7-day cycles

References

  1. SADAL: Kalakonda N, Maerevoet M, Cavallo F, Follows G, Goy A, Vermaat JSP, Casasnovas O, Hamad N, Zijlstra JM, Bakhshi S, Bouabdallah R, Choquet S, Gurion R, Hill B, Jaeger U, Sancho JM, Schuster M, Thieblemont C, De la Cruz F, Egyed M, Mishra S, Offner F, Vassilakopoulos TP, Warzocha K, McCarthy D, Ma X, Corona K, Saint-Martin JR, Chang H, Landesman Y, Joshi A, Wang H, Shah J, Shacham S, Kauffman M, Van Den Neste E, Canales MA. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020 Jul;7(7):e511-e522. link to original article contains dosing details in abstract PubMed NCT02227251

Tisagenlecleucel monotherapy

Regimen

FDA-recommended dose
Study Evidence Efficacy
Schuster et al. 2018 (JULIET) Phase 2 ORR: 59% (95% CI, 44-72)

The range given is the FDA-recommended dose.

Preceding treatment

Immunotherapy

One course

References

  1. JULIET: Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1. link to original article PubMed NCT02445248
    1. Update: Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1403-1415. Epub 2021 Sep 10. link to original article PubMed

Consolidation after salvage therapy

BFR, then allo HSCT

BFR: Bendamustine, Fludarabine, Rituximab

Regimen

Study Evidence
Khouri et al. 2014 (MDACC 2008-0246) Phase 2, <20 pts in this subgroup

Chemotherapy

Targeted therapy

Immunotherapy

GVHD prophylaxis

  • See article for GVHD prophylaxis information

One course

References

  1. MDACC 2008-0246: Khouri IF, Wei W, Korbling M, Turturro F, Ahmed S, Alousi A, Anderlini P, Ciurea S, Jabbour E, Oran B, Popat UR, Rondon G, Bassett RL Jr, Gulbis A. BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD. Blood. 2014 Oct 2;124(14):2306-12. Epub 2014 Aug 21. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00880815
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