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Section editor
	Gaurav Goyal, MD UAB Birmingham, AL GauravGoyalMD

3 regimens on this page 4 variants on this page

Guidelines

Consensus guidelines

2020: Goyal et al. Erdheim-Chester Disease: Consensus Recommendations for Evaluation, Diagnosis, and Treatment in the Molecular Era PubMed

Older

2014: Diamond et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease PubMed

NCCN

NCCN Guidelines - Histiocytic Neoplasms

All lines of therapy

Cobimetinib monotherapy

Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence
Diamond et al. 2019 (MSK 15-216)	2016-NR	Phase 2, <20 pts in this arm (RT)

Targeted therapy

Cobimetinib (Cotellic) 60 mg PO once per day on days 1 to 21

28-day cycles

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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02649972

Sirolimus & Prednisone

Regimen

Study	Evidence
Gianfreda et al. 2015	Pilot, <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/k/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

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 contains dosing details in manuscript PubMed

Vemurafenib monotherapy

Regimen variant #1, 480 mg twice per day

Study	Evidence
Haroche et al. 2014	Pilot, <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

Vemurafenib (Zelboraf) 480 mg PO twice per day

Continued indefinitely

Regimen variant #2, 960 mg twice per day

FDA-recommended dose

Study	Years 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

Vemurafenib (Zelboraf) 960 mg PO twice per day

Duration of treatment not specified

References

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 contains dosing details in manuscript PubMed
VE-BASKET: Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015 Aug 20;373(8):726-736. link to original article contains dosing details in abstract 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 contains dosing details in manuscript link to PMC article PubMed

@@ Line 21: / Line 21: @@
 ===Older===
 *'''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]==
 *[https://www.nccn.org/professionals/physician_gls/pdf/histiocytic_neoplasms.pdf NCCN Guidelines - Histiocytic Neoplasms]
 =All lines of therapy=
 ==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"
@@ Line 44: / Line 41: @@
 |-
 |}
+<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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438729/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30867592 PubMed] NCT02649972
 ==Sirolimus & Prednisone {{#subobject:a5e5cc|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:#fbca7f|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
@@ Line 63: / Line 59: @@
 |-
 |}
+<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
@@ Line 71: / Line 68: @@
 **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'''
+</div></div>
 ===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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26041743 PubMed]
 ==Vemurafenib monotherapy {{#subobject:c184a8|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 480 mg twice per day {{#subobject:#5a234d|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
@@ Line 89: / Line 84: @@
 |}
 ''Note: This is the dose after de-escalation after the first four patients had excess adverse events.''
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *BRAF p.V600E
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Vemurafenib (Zelboraf)]] 480 mg PO twice per day
 '''Continued indefinitely'''
+</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"
@@ Line 112: / Line 110: @@
 |}
 ''Note: This was a basket study that was expanded in the ECD population, as described by Diamond et al. 2017.''
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *BRAF p.V600 alterations
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Vemurafenib (Zelboraf)]] 960 mg PO twice per day
 '''Duration of treatment not specified'''
+</div></div>
 ===References===
 <!-- no pre-pub disclosed -->
@@ Line 124: / Line 124: @@
 # '''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] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26287849 PubMed] NCT01524978
 ## '''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://jamanetwork.com/journals/jamaoncology/fullarticle/2664827 link to original article] '''contains dosing details in manuscript''' [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5844839/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29188284 PubMed]
 [[Category:Erdheim-Chester disease regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Histiocytoses]]

Difference between revisions of "Erdheim-Chester disease"

Revision as of 22:36, 24 January 2023

Contents

Guidelines

Consensus guidelines

Older

NCCN

All lines of therapy

Cobimetinib monotherapy

Regimen

Targeted therapy

References

Sirolimus & Prednisone

Regimen

Immunosuppressive therapy

References

Vemurafenib monotherapy

Regimen variant #1, 480 mg twice per day

Biomarker eligibility criteria

Targeted therapy

Regimen variant #2, 960 mg twice per day

Biomarker eligibility criteria

Targeted therapy

References

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