Langerhans cell histiocytosis

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Section editor
Gaurav Goyal, MD
UAB
Birmingham, AL, USA
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Last updated on 2024-09-06:
12 regimens on this page
12 variants on this page


Note: the majority of the regimens on this page are intended for multi-system Langerhans cell histiocytosis (MS-LCH); many patients with other forms of LCH, such as pulmonary (PLCH) do not necessarily need antineoplastic treatment.

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.

Euro-Histio-Net


International Expert Consensus


NCCN


Untreated

Cytarabine & Methotrexate (CYM)

CYM: CYtarabine, Methotrexate

Regimen

Study Dates of enrollment Evidence
Cao et al. 2020 (MAALCH) 2014-2018 Phase 2

Chemotherapy

  • Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 500 mg/m2)
  • Methotrexate (MTX) 1000 mg/m2 IV continuous infusion over 24 hours, started on day 1

35-day cycle for 6 cycles

References

  1. MAALCH: Cao XX, Li J, Zhao AL, He TH, Gao XM, Cai HC, Zhang L, Zhang Y, Feng J, Zhu TN, Niu N, Sun J, Liang ZY, Duan MH, Zhou DB. Methotrexate and cytarabine for adult patients with newly diagnosed Langerhans cell histiocytosis: A single arm, single center, prospective phase 2 study. Am J Hematol. 2020 Sep;95(9):E235-E238. Epub 2020 Jun 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02389400


Etoposide & Methylprednisolone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gadner et al. 2001 (LCH-I) 1991-1995 Phase 3 (E-switch-ic) Vinblastine & HDMP Did not meet efficacy endpoints

Chemotherapy

Glucocorticoid therapy

21-day cycle for 8 cycles

References

  1. 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed


Etoposide, Vinblastine, Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gadner et al. 2007 (LCH-II) 1996-2001 Phase 3 (E-esc) Vinblastine & Prednisone Did not meet primary endpoint of rapid response

Chemotherapy

  • Etoposide (Vepesid) as follows:
    • Cycle 1: 150 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
    • Cycles 2 to 7: 150 mg/m2 IV over 60 minutes once on day 1
  • Vinblastine (Velban) as follows:
    • Cycle 1: 6 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36
    • Cycles 2 to 7: 6 mg/m2 IV bolus once on day 1

Glucocorticoid therapy

  • Prednisone (Sterapred) as follows:
    • Cycle 1: 40 mg/m2/day PO split three times per day for 4 weeks, then tapering off over 2 weeks
    • Cycles 2 to 7: 40 mg/m2/day PO split three times per day on days 1 to 5

6-week course, then 21-day cycle for 6 cycles

References

  1. LCH-II: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN57679341


Methotrexate, Vinblastine, Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gadner et al. 2013 (LCH-III) 2001-2008 Phase 3 (E-esc) Vinblastine & Prednisone Did not meet primary endpoint of early progression at week 6 and response at week 12

Chemotherapy

Glucocorticoid therapy

6-week course

Subsequent treatment

  • See paper for details of treatment beyond induction.

References

  1. LCH-III: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00276757


Vinblastine & Methylprednisolone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gadner et al. 2001 (LCH-I) 1991-1995 Phase 3 (E-switch-ic) Etoposide & HDMP Did not meet efficacy endpoints

Chemotherapy

Glucocorticoid therapy

7-day cycle for 24 cycles

References

  1. LCH-I: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed


Vinblastine & Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gadner et al. 2007 (LCH-II) 1996-2001 Phase 3 (C) Etoposide, Vinblastine, Prednisone Did not meet primary endpoint of rapid response
Gadner et al. 2013 (LCH-III) 2001-2008 Phase 3 (C) Methotrexate, Vinblastine, Prednisone Did not meet primary endpoint of early progression at week 6 and response at week 12

Chemotherapy

  • Vinblastine (Velban) as follows:
    • Cycle 1: 6 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36
    • Cycles 2 to 7: 6 mg/m2 IV bolus once on day 1

Glucocorticoid therapy

  • Prednisone (Sterapred) as follows:
    • Cycle 1: 40 mg/m2/day PO split three times per day for 4 weeks, then tapering off over 2 weeks
    • Cycles 2 to 7: 40 mg/m2/day PO split three times per day on days 1 to 5

6-week course, then 21-day cycle for 6 cycles

References

  1. LCH-II: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN57679341
  2. LCH-III: 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. link to original article PubMed NCT00276757


Relapsed or refractory

Cladribine monotherapy

Regimen

Study Dates of enrollment Evidence
Weitzman et al. 2009 (LCH-S-98) 1999-04 to not reported Phase 2

Chemotherapy

21-day cycle for up to 6 cycles

References

  1. LCH-S-98: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed


Cladribine & Cytarabine

Regimen

Study Dates of enrollment Evidence
Donadieu et al. 2015 (LCH-S-2005) 2005-04 to 2010-11 Phase 2

Chemotherapy

  • Cladribine (Leustatin) by the following weight-based criteria:
    • 10 kg or more: 9 mg/m2 IV over 2 hours once per day on days 2 to 6, should not be administered simultaneously with cytarabine
    • Less than 10 kg: 0.3 mg/kg IV over 2 hours once per day on days 2 to 6, should not be administered simultaneously with cytarabine
  • Cytarabine (Ara-C) 500 mg/m2 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

Subsequent treatment

  • LCH-S-2005, patients with a good response: Cladribine consolidation

References

  1. LCH-S-2005: 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed


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)

Note: there were N=2 patients with LCH; it was unclear if they were untreated or previously treated.

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


Vemurafenib monotherapy

Regimen

Study Dates of enrollment Evidence
Hyman et al. 2015 (VE-BASKET) 2012-2014 Phase 2, fewer than 20 pts in this arm

Note: This was part of a basket trial, all patients had BRAF p.V600E mutations. A minority (7/18, 39%) of participants were untreated.

Targeted therapy

Duration of treatment not specified

References

  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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed


Relapsed or refractory, consolidation

Cladribine monotherapy

Regimen

Study Dates of enrollment Evidence
Donadieu et al. 2015 (LCH-S-2005) 2005-04 to 2010-11 Phase 2

Preceding treatment

Chemotherapy

21-day cycle for 2 cycles

Subsequent treatment

References

  1. LCH-S-2005: 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed


Relapsed or refractory, maintenance

Mercaptopurine, Methotrexate, Vinblastine, Prednisolone

Regimen

Study Dates of enrollment Evidence
Donadieu et al. 2015 (LCH-S-2005) 2005-04 to 2010-11 Phase 2

Preceding treatment

Chemotherapy

Glucocorticoid therapy

14-day cycle for 39 cycles (18 months)

References

  1. LCH-S-2005: 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed


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