Difference between revisions of "Erdheim-Chester disease"

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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]].
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{{#lst:Editorial board transclusions|hist}}
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
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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: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} variants 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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 +
=Guidelines=
 +
'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 +
==Consensus guidelines==
 +
*'''2020:''' Goyal et al. [https://doi.org/10.1182/blood.2019003507 Erdheim-Chester Disease: Consensus Recommendations for Evaluation, Diagnosis, and Treatment in the Molecular Era] [https://pubmed.ncbi.nlm.nih.gov/32187362/ PubMed]
  
−
=Erdheim-Chester disease (ECD)=
+
*'''2014:''' Diamond et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110656/ Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease] [https://pubmed.ncbi.nlm.nih.gov/24850756/ PubMed]
 +
==[https://www.nccn.org NCCN]==
 +
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1502 NCCN Guidelines - Histiocytic Neoplasms].''
  
−
==Sirolimus & Prednisone {{#subobject:a5e5cc|Regimen=1}}==
+
=All lines of therapy=
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
==Cobimetinib monotherapy {{#subobject:a6f6dd|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:#fecb7f|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%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438729/ Diamond et al. 2019 (MSK 15-216)]
 +
|2016 to not reported
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts in this arm (RT)
 
|-
 
|-
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|[[#top|back to top]]
 
 
|}
 
|}
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+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Cobimetinib (Cotellic)]] 60 mg PO once per day on days 1 to 21
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
# '''MSK 15-216:''' Diamond EL, Durham BH, Ulaner GA, Drill E, Buthorn J, Ki M, Bitner L, Cho H, Young RJ, Francis JH, Rampal R, Lacouture M, Brody LA, Ozkaya N, Dogan A, Rosen N, Iasonos A, Abdel-Wahab O, Hyman DM. Efficacy of MEK inhibition in patients with histiocytic neoplasms. Nature. 2019 Mar;567(7749):521-524. Epub 2019 Mar 13. [https://doi.org/10.1038/s41586-019-1012-y link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438729/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30867592/ PubMed] [https://clinicaltrials.gov/study/NCT02649972 NCT02649972]
 +
==Sirolimus & Prednisone {{#subobject:a5e5cc|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:#fbca7f|Variant=1}}===
 
===Regimen {{#subobject:#fbca7f|Variant=1}}===
−
{| border="1" style="text-align:center;" !align="left"  
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{| class="wikitable sortable" style="width: 60%; text-align:center;"  
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|'''Study'''
+
!style="width: 33%"|Study
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/126/10/1163.long Gianfreda et al. 2015]
+
|[https://doi.org/10.1182/blood-2015-01-620377 Gianfreda et al. 2015]
−
|style="background-color:#ff0000"|Pilot, <20 pts in this arm
+
|2005-06 to not reported
 +
|style="background-color:#ffffbe"|Pilot, fewer than 20 pts in this arm
 
|-
 
|-
 
|}
 
|}
−
====Chemotherapy====
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunosuppressive therapy====
 
*[[Sirolimus (Rapamune)]] 2 mg PO once per day, titrated to achieve a blood level of 8 to 12 ng/mL
 
*[[Sirolimus (Rapamune)]] 2 mg PO once per day, titrated to achieve a blood level of 8 to 12 ng/mL
 
*[[Prednisone (Sterapred)]] as follows:
 
*[[Prednisone (Sterapred)]] as follows:
−
**Month 1: 0.75 mg/kg/day PO
+
**Cycle 1: 0.75 mg/kg/day PO
−
**Month 2: 0.5 mg/k/day PO
+
**Cycle 2: 0.5 mg/kg/day PO
−
**Months 3 & 4: 0.25 mg/kg/day PO
+
**Cycles 3 & 4: 0.25 mg/kg/day PO
−
**Months 5 & 6: 0.125 mg/kg/day PO
+
**Cycles 5 & 6: 0.125 mg/kg/day PO
−
**Month 7 onwards: tapered to a dose of 2.5 to 5 mg PO once per day
+
**Cycle 7 onwards: tapered to a dose of 2.5 to 5 mg PO once per day
−
 
+
'''Monthly cycle for up to 24 cycles (2 years), with optional extension beyond 2 years'''
−
'''Given for up to 2 years for responders and stable disease, with optional extension beyond 2 years'''
+
</div></div>
  
 
===References===
 
===References===
−
# Gianfreda D, Nicastro M, Galetti M, Alberici F, Corradi D, Becchi G, Baldari G, De Filippo M, Ferretti S, Moroni G, Foti R, Di Gangi M, Jeannin G, Saffroy R, Emile JF, Buzio C, Vaglio A. Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial. Blood. 2015 Sep 3;126(10):1163-71. Epub 2015 Jun 3. [http://www.bloodjournal.org/content/126/10/1163.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26041743 PubMed]
+
# Gianfreda D, Nicastro M, Galetti M, Alberici F, Corradi D, Becchi G, Baldari G, De Filippo M, Ferretti S, Moroni G, Foti R, Di Gangi M, Jeannin G, Saffroy R, Emile JF, Buzio C, Vaglio A. Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial. Blood. 2015 Sep 3;126(10):1163-71. Epub 2015 Jun 3. [https://doi.org/10.1182/blood-2015-01-620377 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26041743/ PubMed] ACTRN12613001321730
  
 
==Vemurafenib monotherapy {{#subobject:c184a8|Regimen=1}}==
 
==Vemurafenib monotherapy {{#subobject:c184a8|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
−
|-
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===Regimen variant #1, 480 mg twice per day {{#subobject:#5a234d|Variant=1}}===
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|[[#top|back to top]]
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{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
|}
+
!style="width: 33%"|Study
−
 
+
!style="width: 33%"|Dates of enrollment
−
===Regimen #1 {{#subobject:#84a4d6|Variant=1}}===
+
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ Hyman et al. 2015]
 
−
|style="background-color:#ff0000"|Phase II, <20 pts in this arm
 
−
|-
 
−
|}
 
−
''This was part of a basket trial, all patients had BRAF V600E mutations.''
 
−
====Chemotherapy====
 
−
*[[Vemurafenib (Zelboraf)]] 960 mg PO BID
 
−
 
 
−
'''Duration of treatment not specified'''
 
−
 
 
−
===Regimen #2 {{#subobject:#5a234d|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[http://jco.ascopubs.org/content/33/5/411.full Haroche et al. 2014]
 
−
|style="background-color:#ff0000"|Pilot, <20 pts
 
−
|-
 
−
|}
 
−
''Patients enrolled all had BRAF V600E mutation. This is the dose after de-escalation after the first four patients had excess adverse events.''
 
−
====Chemotherapy====
 
−
*[[Vemurafenib (Zelboraf)]] 480 mg PO BID
 
−
 
 
−
'''Given until progression of disease or unacceptable toxicity'''
 
−
 
 
−
===References===
 
−
<!-- no pre-pub disclosed -->
 
−
# Haroche J, Cohen-Aubart F, Emile JF, Maksud P, Drier A, Tolédano D, Barete S, Charlotte F, Cluzel P, Donadieu J, Benameur N, Grenier PA, Besnard S, Ory JP, Lifermann F, Idbaih A, Granel B, Graffin B, Hervier B, Arnaud L, Amoura Z. Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With BRAFV600E-Mutated Erdheim-Chester Disease. J Clin Oncol. 2015 Feb 10;33(5):411-8. Epub 2014 Nov 24. [http://jco.ascopubs.org/content/33/5/411.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25422482 PubMed]
 
−
# 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):726-736. [http://www.nejm.org/doi/full/10.1056/NEJMoa1502309 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26287849 PubMed]
 
−
 
 
−
=Langerhans cell histiocytosis (LCH)=
 
−
 
 
−
==Cladribine monotherapy {{#subobject:da32fb|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
−
===Regimen {{#subobject:1ef1c0|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"  
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[http://onlinelibrary.wiley.com/doi/10.1002/pbc.22229/abstract Weitzman et al. 2009 (LCH-S-98)]
 
−
|style="background-color:#EEEE00"|Phase II
 
−
|-
 
−
|}
 
−
To be completed
 
−
====Chemotherapy====
 
−
*[[Cladribine (Leustatin)]]
 
−
 
 
−
===References===
 
−
# Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Pötschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH). results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. [http://onlinelibrary.wiley.com/doi/10.1002/pbc.22229/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19731321 PubMed]
 
−
 
 
−
==Cladribine & Cytarabine {{#subobject:4c5b41|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
−
===Regimen {{#subobject:7b85e8|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ Donadieu et al. 2015]
 
−
|style="background-color:#EEEE00"|Phase II
 
−
|-
 
−
|}
 
−
====Chemotherapy, induction====
 
−
*[[Cladribine (Leustatin)]] 9 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 6, '''should not be administered simultaneously with cytarabine'''
 
−
**Children weighing less than 10 kg received a dose of 0.3 mg/kg/day
 
−
*[[Cytarabine (Cytosar)]] 500 mg/m<sup>2</sup> IV over 2 hours twice per day on days 1 to 5, '''should not be administered simultaneously with cladribine'''
 
−
 
 
−
'''35-day cycle for 2 or more cycles'''
 
−
 
 
−
''Patients with a "good response" proceeded to consolidation therapy:''
 
−
 
 
−
====Chemotherapy, consolidation====
 
−
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
 
 
−
'''21-day cycle for 2 cycles, followed by:'''
 
−
 
 
−
====Chemotherapy, maintenance====
 
−
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once every 2 weeks for 6 months
 
−
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5 of every 2nd week for 6 months
 
−
*[[Mercaptopurine (Purinethol)]] 50 mg/m<sup>2</sup> PO once per day for 18 months
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once per week for 18 months
 
−
 
 
−
'''Total of 18 months of maintenance'''
 
−
 
 
−
===References===
 
−
<!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. -->
 
−
# Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. [http://www.bloodjournal.org/content/126/12/1415.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26194764 PubMed]
 
−
 
 
−
==Etoposide & Prednisone {{#subobject:566a87|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://doi.org/10.1200/jco.2014.57.1950 Haroche et al. 2014]
−
|}
+
|Not reported
−
 
+
|style="background-color:#ffffbe"|Pilot, fewer than 20 pts
−
===Regimen {{#subobject:#3c6b84|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)]
 
−
|style="background-color:#00CD00"|Phase III
 
−
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
−
To be completed
+
''Note: This is the dose after de-escalation after the first four patients had excess adverse events.''
−
====Chemotherapy====
+
<div class="toccolours" style="background-color:#fdcdac">
−
*[[Etoposide (Vepesid)]]
+
====Biomarker eligibility criteria====
−
*[[Prednisone (Sterapred)]]
+
*BRAF p.V600E
−
 
+
</div>
−
===References===
+
<div class="toccolours" style="background-color:#b3e2cd">
−
# Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. [http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11343051 PubMed]
+
====Targeted therapy====
−
 
+
*[[Vemurafenib (Zelboraf)]] 480 mg PO twice per day
−
==Etoposide, Vinblastine, Prednisone {{#subobject:5145a8|Regimen=1}}==
+
'''Continued indefinitely'''
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 960 mg twice per day {{#subobject:#84a4d6|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
−
 
+
{| class="wikitable" style="width: 60%; text-align:center;"  
−
===Regimen {{#subobject:#7ace0e|Variant=1}}===
+
!style="width: 33%"|Study
−
{| border="1" style="text-align:center;" !align="left"  
+
!style="width: 33%"|Dates of enrollment
−
|'''Study'''
+
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ Hyman et al. 2015 (VE-BASKET)]
−
|style="background-color:#00CD00"|Phase III
+
|2012-2014
−
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
+
| style="background-color:#91cf61" |Phase 2 (RT)
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
−
''Total duration of therapy is 24 weeks.''
+
''Note: This was a basket study that was expanded in the ECD population, as described by Diamond et al. 2017.''
−
====Chemotherapy, initial====
+
<div class="toccolours" style="background-color:#fdcdac">
−
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 1 hour once per week
+
====Biomarker eligibility criteria====
−
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per week
+
*BRAF p.V600 alterations
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID for 4 weeks, then tapering off over 2 weeks
+
</div>
−
 
+
<div class="toccolours" style="background-color:#b3e2cd">
−
'''6-week course, followed by:'''
+
====Targeted therapy====
−
 
+
*[[Vemurafenib (Zelboraf)]] 960 mg PO twice per day
−
====Chemotherapy, continuation====
 
−
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 1 hour once on day 1
 
−
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once on day 1
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID on days 1 to 5
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===References===
 
−
# Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. [http://www.bloodjournal.org/content/111/5/2556.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18089850 PubMed]
 
−
 
 
−
==Methotrexate, Vinblastine, Prednisone {{#subobject:2d772c|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
−
===Regimen {{#subobject:#f569ce|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
 
−
|style="background-color:#00CD00"|Phase III
 
−
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|}
 
−
To be completed
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Vinblastine (Velban)]]
 
−
*[[Prednisone (Sterapred)]]
 
−
 
 
−
===References===
 
−
# Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. [http://www.bloodjournal.org/content/121/25/5006.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23589673 PubMed]
 
−
 
 
−
==Vemurafenib monotherapy {{#subobject:953978|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
−
===Regimen {{#subobject:#73ec1b|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ Hyman et al. 2015]
 
−
|style="background-color:#ff0000"|Phase II, <20 pts in this arm
 
−
|-
 
−
|}
 
−
''This was part of a basket trial, all patients had BRAF V600E mutations.''
 
−
====Chemotherapy====
 
−
*[[Vemurafenib (Zelboraf)]] 960 mg PO BID
 
−
 
 
 
'''Duration of treatment not specified'''
 
'''Duration of treatment not specified'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# 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):726-736. [http://www.nejm.org/doi/full/10.1056/NEJMoa1502309 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26287849 PubMed]
+
<!-- no pre-pub disclosed -->
−
 
+
# Haroche J, Cohen-Aubart F, Emile JF, Maksud P, Drier A, Tolédano D, Barete S, Charlotte F, Cluzel P, Donadieu J, Benameur N, Grenier PA, Besnard S, Ory JP, Lifermann F, Idbaih A, Granel B, Graffin B, Hervier B, Arnaud L, Amoura Z. Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAFV600E-mutated Erdheim-Chester disease. J Clin Oncol. 2015 Feb 10;33(5):411-8. Epub 2014 Nov 24. [https://doi.org/10.1200/jco.2014.57.1950 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25422482/ PubMed]
−
==Vinblastine & Prednisone {{#subobject:378322|Regimen=1}}==
+
# '''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):726-736. [https://doi.org/10.1056/NEJMoa1502309 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26287849/ PubMed] [https://clinicaltrials.gov/study/NCT01524978 NCT01524978]
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
## '''Update:''' Diamond EL, Subbiah V, Lockhart AC, Blay JY, Puzanov I, Chau I, Raje NS, Wolf J, Erinjeri JP, Torrisi J, Lacouture M, Elez E, Martínez-Valle F, Durham B, Arcila ME, Ulaner G, Abdel-Wahab O, Pitcher B, Makrutzki M, Riehl T, Baselga J, Hyman DM. Vemurafenib for BRAF V600-mutant Erdheim-Chester disease and Langerhans cell histiocytosis: analysis of data from the histology-independent, phase 2, open-label VE-BASKET Study. JAMA Oncol. 2018 Mar 1;4(3):384-388. Epub 2017 Nov 29. [https://doi.org/10.1001/jamaoncol.2017.5029 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5844839/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29188284/ PubMed]
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
−
===Regimen {{#subobject:#bf6a74|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)]
 
−
|style="background-color:#00CD00"|Phase III
 
−
|[[Histiocytoses#Etoposide_.26_Prednisone|Etoposide & Prednisone]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)]
 
−
|style="background-color:#00CD00"|Phase III
 
−
|[[Histiocytoses#Etoposide.2C_Vinblastine.2C_Prednisone|Etoposide, Vinblastine, Prednisone]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
 
−
|style="background-color:#00CD00"|Phase III
 
−
|[[Histiocytoses#Methotrexate.2C_Vinblastine.2C_Prednisone|Methotrexate, Vinblastine, Prednisone]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|}
 
−
''Total duration of therapy is 24 weeks, in LCH-II.''
 
−
====Chemotherapy, initial====
 
−
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per week
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID for 4 weeks, then tapering off over 2 weeks
 
−
 
 
−
'''6-week course, followed by:'''
 
−
 
 
−
====Chemotherapy, continuation====
 
−
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once on day 1
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID on days 1 to 5
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===References===
 
−
# Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. [http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11343051 PubMed]
 
−
# Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. [http://www.bloodjournal.org/content/111/5/2556.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18089850 PubMed]
 
−
# Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. [http://www.bloodjournal.org/content/121/25/5006.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23589673 PubMed]
 
−
 
 
 
[[Category:Erdheim-Chester disease regimens]]
 
[[Category:Erdheim-Chester disease regimens]]
−
[[Category:Langerhans cell histiocytosis regimens]]
 
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Disease index]]
+
[[Category:Histiocytoses]]

Latest revision as of 21:50, 24 July 2024

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Section editor
GauravGoyal.jpg
 Gaurav Goyal, MD
UAB
Birmingham, AL, USA
LinkedIn
3 regimens on this page
4 variants on this page


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

Consensus guidelines

NCCN

All lines of therapy

Cobimetinib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Diamond et al. 2019 (MSK 15-216) 2016 to not reported Phase 2, fewer than 20 pts in this arm (RT)

Targeted therapy

28-day cycles

References

  1. MSK 15-216: Diamond EL, Durham BH, Ulaner GA, Drill E, Buthorn J, Ki M, Bitner L, Cho H, Young RJ, Francis JH, Rampal R, Lacouture M, Brody LA, Ozkaya N, Dogan A, Rosen N, Iasonos A, Abdel-Wahab O, Hyman DM. Efficacy of MEK inhibition in patients with histiocytic neoplasms. Nature. 2019 Mar;567(7749):521-524. Epub 2019 Mar 13. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02649972

Sirolimus & Prednisone

Regimen

Study Dates of enrollment Evidence
Gianfreda et al. 2015 2005-06 to not reported Pilot, fewer than 20 pts in this arm

Immunosuppressive therapy

  • Sirolimus (Rapamune) 2 mg PO once per day, titrated to achieve a blood level of 8 to 12 ng/mL
  • Prednisone (Sterapred) as follows:
    • Cycle 1: 0.75 mg/kg/day PO
    • Cycle 2: 0.5 mg/kg/day PO
    • Cycles 3 & 4: 0.25 mg/kg/day PO
    • Cycles 5 & 6: 0.125 mg/kg/day PO
    • Cycle 7 onwards: tapered to a dose of 2.5 to 5 mg PO once per day

Monthly cycle for up to 24 cycles (2 years), with optional extension beyond 2 years

References

  1. Gianfreda D, Nicastro M, Galetti M, Alberici F, Corradi D, Becchi G, Baldari G, De Filippo M, Ferretti S, Moroni G, Foti R, Di Gangi M, Jeannin G, Saffroy R, Emile JF, Buzio C, Vaglio A. Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial. Blood. 2015 Sep 3;126(10):1163-71. Epub 2015 Jun 3. link to original article dosing details in manuscript have been reviewed by our editors PubMed ACTRN12613001321730

Vemurafenib monotherapy

Regimen variant #1, 480 mg twice per day

Study Dates of enrollment Evidence
Haroche et al. 2014 Not reported Pilot, fewer than 20 pts

Note: This is the dose after de-escalation after the first four patients had excess adverse events.

Biomarker eligibility criteria

  • BRAF p.V600E

Targeted therapy

Continued indefinitely


Regimen variant #2, 960 mg twice per day

FDA-recommended dose
Study Dates of enrollment Evidence
Hyman et al. 2015 (VE-BASKET) 2012-2014 Phase 2 (RT)

Note: This was a basket study that was expanded in the ECD population, as described by Diamond et al. 2017.

Biomarker eligibility criteria

  • BRAF p.V600 alterations

Targeted therapy

Duration of treatment not specified

References

  1. Haroche J, Cohen-Aubart F, Emile JF, Maksud P, Drier A, Tolédano D, Barete S, Charlotte F, Cluzel P, Donadieu J, Benameur N, Grenier PA, Besnard S, Ory JP, Lifermann F, Idbaih A, Granel B, Graffin B, Hervier B, Arnaud L, Amoura Z. Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAFV600E-mutated Erdheim-Chester disease. J Clin Oncol. 2015 Feb 10;33(5):411-8. Epub 2014 Nov 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed
  2. 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):726-736. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT01524978
    1. Update: Diamond EL, Subbiah V, Lockhart AC, Blay JY, Puzanov I, Chau I, Raje NS, Wolf J, Erinjeri JP, Torrisi J, Lacouture M, Elez E, Martínez-Valle F, Durham B, Arcila ME, Ulaner G, Abdel-Wahab O, Pitcher B, Makrutzki M, Riehl T, Baselga J, Hyman DM. Vemurafenib for BRAF V600-mutant Erdheim-Chester disease and Langerhans cell histiocytosis: analysis of data from the histology-independent, phase 2, open-label VE-BASKET Study. JAMA Oncol. 2018 Mar 1;4(3):384-388. Epub 2017 Nov 29. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
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