Difference between revisions of "Langerhans cell histiocytosis"
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|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)] | |[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)] | ||
|1991-1995 | |1991-1995 | ||
| − | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
|[[#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]] | |[[#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]] | ||
|style="background-color:#ffffbf"|Did not meet efficacy endpoints | |style="background-color:#ffffbf"|Did not meet efficacy endpoints | ||
| Line 94: | Line 94: | ||
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)] | |[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)] | ||
|1996-2001 | |1996-2001 | ||
| − | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]] | |[[#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of rapid response | |style="background-color:#ffffbf"|Did not meet primary endpoint of rapid response | ||
| Line 133: | Line 133: | ||
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)] | |[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)] | ||
|2001-2008 | |2001-2008 | ||
| − | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]] | |[[#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of early progression at week 6 and response at week 12 | |style="background-color:#ffffbf"|Did not meet primary endpoint of early progression at week 6 and response at week 12 | ||
| Line 163: | Line 163: | ||
|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)] | |[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)] | ||
|1991-1995 | |1991-1995 | ||
| − | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
|[[#Etoposide_.26_Prednisone|Etoposide & Prednisone]] | |[[#Etoposide_.26_Prednisone|Etoposide & Prednisone]] | ||
|style="background-color:#ffffbf"|Did not meet efficacy endpoints | |style="background-color:#ffffbf"|Did not meet efficacy endpoints | ||
| Line 169: | Line 169: | ||
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)] | |[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)] | ||
|1996-2001 | |1996-2001 | ||
| − | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Etoposide.2C_Vinblastine.2C_Prednisone|Etoposide, Vinblastine, Prednisone]] | |[[#Etoposide.2C_Vinblastine.2C_Prednisone|Etoposide, Vinblastine, Prednisone]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of rapid response | |style="background-color:#ffffbf"|Did not meet primary endpoint of rapid response | ||
| Line 175: | Line 175: | ||
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)] | |[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)] | ||
|2001-2008 | |2001-2008 | ||
| − | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Methotrexate.2C_Vinblastine.2C_Prednisone|Methotrexate, Vinblastine, Prednisone]] | |[[#Methotrexate.2C_Vinblastine.2C_Prednisone|Methotrexate, Vinblastine, Prednisone]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of early progression at week 6 and response at week 12 | |style="background-color:#ffffbf"|Did not meet primary endpoint of early progression at week 6 and response at week 12 | ||
Revision as of 15:00, 12 February 2022
| Section editor | |
|---|---|
 |
Gaurav Goyal, MD UAB Birmingham, AL  GauravGoyalMD
|
11 regimens on this page
11 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
Euro-Histio-Net
- 2013: Management of adult patients with Langerhans cell histiocytosis: Recommendations from an expert panel on behalf of Euro-Histio-Net
- 2013: Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years
NCCN
Untreated
Cytarabine & Methotrexate (CYM)
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CYM: CYtarabine, Methotrexate
Regimen
| Study | Years of enrollment | Evidence |
|---|---|---|
| Cao et al. 2020 (MAALCH) | 2014-2018 | Phase II |
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
- 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 contains verified protocol PubMed NCT02389400
Etoposide & Prednisone
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Regimen
| Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Gadner et al. 2001 (LCH-I) | 1991-1995 | Phase 3 (E-switch-ic) | Vinblastine & Prednisone | Did not meet efficacy endpoints |
To be completed
Chemotherapy
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. link to original article PubMed
Etoposide, Vinblastine, Prednisone
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Protocol
| Study | Years 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 |
Total duration of therapy is 24 weeks.
Chemotherapy, initial
- Etoposide (Vepesid) 150 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
- Vinblastine (Velban) 6 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36
- Prednisone (Sterapred) 40 mg/m2/day split three times per day for 4 weeks, then tapering off over 2 weeks
6-week course, followed by:
Chemotherapy, continuation
- Etoposide (Vepesid) 150 mg/m2 IV over 60 minutes once on day 1
- Vinblastine (Velban) 6 mg/m2 IV bolus once on day 1
- Prednisone (Sterapred) 40 mg/m2/day split three times per day on days 1 to 5
21-day cycle for 6 cycles
References
- 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 contains verified protocol PubMed ISRCTN57679341
Methotrexate, Vinblastine, Prednisone
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Regimen
| Study | Years 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 |
To be completed
Chemotherapy
References
- 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
Vinblastine & Prednisone
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Protocol
| Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Gadner et al. 2001 (LCH-I) | 1991-1995 | Phase 3 (E-switch-ic) | Etoposide & Prednisone | Did not meet efficacy endpoints |
| 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 |
Total duration of therapy is 24 weeks, in LCH-II.
Chemotherapy, initial
- Vinblastine (Velban) 6 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36
- Prednisone (Sterapred) 40 mg/m2/day split three times per day for 4 weeks, then tapering off over 2 weeks
6-week course, followed by:
Chemotherapy, continuation
- Vinblastine (Velban) 6 mg/m2 IV bolus once on day 1
- Prednisone (Sterapred) 40 mg/m2/day split three times per day on days 1 to 5
21-day cycle for 6 cycles
References
- 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 PubMed
- 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 contains verified protocol PubMed
- 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
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Regimen
| Study | Evidence |
|---|---|
| Weitzman et al. 2009 (LCH-S-98) | Phase II |
To be completed
Chemotherapy
References
- 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 PubMed
Cladribine & Cytarabine
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Regimen
| Study | Evidence |
|---|---|
| Donadieu et al. 2015 (LCH-S-2005) | Phase II |
Chemotherapy
- Cladribine (Leustatin) 9 mg/m2 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 (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
- Patients with a "good response": Cladribine consolidation
References
- 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 contains verified protocol link to PMC article PubMed
Cobimetinib monotherapy
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Regimen
| Study | Evidence |
|---|---|
| Diamond et al. 2019 (MSK 15-216) | Pilot, <20 pts in this arm |
Note: there were N=2 patients with LCH; it was unclear if they were untreated or previously treated.
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 verified protocol link to PMC article PubMed
Vemurafenib monotherapy
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Regimen
| Study | Evidence |
|---|---|
| Hyman et al. 2015 (VE-BASKET) | Phase II, <20 pts in this arm |
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
- Vemurafenib (Zelboraf) 960 mg PO twice per day
Duration of treatment not specified
References
- 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 verified protocol link to PMC article PubMed
Relapsed or refractory, consolidation
Cladribine monotherapy
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Regimen
| Study | Evidence |
|---|---|
| Donadieu et al. 2015 (LCH-S-2005) | Phase II |
Preceding treatment
Chemotherapy
- Cladribine (Leustatin) 5 mg/m2 IV once per day on days 1 to 3
21-day cycle for 2 cycles
Subsequent treatment
References
- 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 contains verified protocol link to PMC article PubMed
Relapsed or refractory, maintenance
Mercaptopurine, Methotrexate, Vinblastine, Prednisolone
| back to top |
Regimen
| Study | Evidence |
|---|---|
| Donadieu et al. 2015 (LCH-S-2005) | Phase II |
Preceding treatment
- Cladribine x 2
Chemotherapy
- Mercaptopurine (6-MP) 50 mg/m2 PO once per day
- Methotrexate (MTX) 20 mg/m2 PO once per day on days 1 & 8
- Vinblastine (Velban) as follows:
- Cycles 1 to 13: 6 mg/m2 IV once on day 1
- Prednisolone (Millipred) as follows:
- Cycles 1 to 13: 40 mg/m2 PO once per day on days 1 to 5
14-day cycles for 39 cycles (18 months)
References
- 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 contains verified protocol link to PMC article PubMed