Erdheim-Chester disease

Section editor
	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

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

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

NCCN

• NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Histiocytic Neoplasms.

All lines of therapy

Cobimetinib monotherapy

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence
Diamond et al. 2019 (MSK 15-216)	2016-NR	Phase 2, fewer than 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

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 contains dosing details in manuscript link to PMC article PubMed NCT02649972

Sirolimus & Prednisone

Regimen

Study	Evidence
Gianfreda et al. 2015	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 contains dosing details in manuscript PubMed

Vemurafenib monotherapy

Regimen variant #1, 480 mg twice per day

Study	Evidence
Haroche et al. 2014	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

• Vemurafenib (Zelboraf) 480 mg PO twice per day

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

• Vemurafenib (Zelboraf) 960 mg PO twice per day

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 contains dosing details in manuscript 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 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