Systemic mastocytosis

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Note: most published trials in this area are for "advanced systemic mastocytosis", which includes more than one WHO category. See individual regimens for details.
Last updated on 2024-07-23:7 regimens on this page
13 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.
==NCCN==
*NCCN Guidelines - Systemic Mastocytosis
**2024: Gotlib et al. NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024 EuroPMC
=All lines of therapy=
==Avapritinib monotherapy==
===Regimen variant #1, 25 mg/day===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Gotlib et al. 2023 (PIONEER)	2020-09 to 2022-01 	Randomized Phase 2 (E-RT-esc)	Placebo 	Better mean change in total symptom score (primary endpoint)
Note: this is the dosing for indolent systemic mastocytosis (ISM).
====Targeted therapy====
*Avapritinib (Ayvakit) 25 mg PO once per day
Continued indefinitely
===Regimen variant #2, 200 mg/day===
FDA-recommended dose
Study 	Dates of enrollment	Evidence
DeAngelo et al. 2021 (EXPLORER)	2016-2020 	Phase 1 (RT)
Gotlib et al. 2021 (PATHFINDER)	2018-2020 	Phase 2 (RT)
Note: this is the dosing for advanced systemic mastocytosis (ASM).
====Targeted therapy====
*Avapritinib (Ayvakit) 200 mg PO once per day
Continued indefinitely
===References===
#EXPLORER: DeAngelo DJ, Radia DH, George TI, Robinson WA, Quiery AT, Drummond MW, Bose P, Hexner EO, Winton EF, Horny HP, Tugnait M, Schmidt-Kittler O, Evans EK, Lin HM, Mar BG, Verstovsek S, Deininger MW, Gotlib J. Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. Nat Med. 2021 Dec;27(12):2183-2191. Epub 2021 Dec 6. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT02561988
#PATHFINDER: Gotlib J, Reiter A, Radia DH, Deininger MW, George TI, Panse J, Vannucchi AM, Platzbecker U, Alvarez-Twose I, Mital A, Hermine O, Dybedal I, Hexner EO, Hicks LK, Span L, Mesa R, Bose P, Pettit KM, Heaney ML, Oh ST, Sen J, Lin HM, Mar BG, DeAngelo DJ. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. Nat Med. 2021 Dec;27(12):2192-2199. Epub 2021 Dec 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03580655
#PIONEER: Gotlib J, Castells M, Elberink HO, Siebenhaar F, Hartmann K, Broesby-Olsen S, George TI, Panse J, Alvarez-Twose I, Radia DH, Tashi T, Bulai Livideanu C, Sabato V, Heaney M, Van Daele P, Cerquozzi S, Dybedal I, Reiter A, Pongdee T, Barete S, Ustun C, Schwartz L, Ward BR, Schafhausen P, Vadas P, Bose P, DeAngelo DJ, Rein L, Vachhani P, Triggiani M, Bonadonna P, Rafferty M, Butt NM, Oh ST, Wortmann F, Ungerstedt J, Guilarte M, Taparia M, Kuykendall AT, Arana Yi C, Ogbogu P, Gaudy-Marqueste C, Mattsson M, Shomali W, Giannetti MP, Bidollari I, Lin HM, Sulllivan E, Mar B, Scherber R, Roche M, Akin C, Maurer M. Avapritinib versus Placebo in Indolent Systemic Mastocytosis. NEJM Evid. 2023 Jun;2(6):EVIDoa2200339. Epub 2023 May 23. link to original article EuroPMC NCT03731260
==Cladribine monotherapy==
===Regimen variant #1, 0.13 mg/kg===
Study 	Dates of enrollment	Evidence
Kluin-Nelemans et al. 2003	2001-08 to 2003-06 	Pilot, fewer than 20 patients reported
====Chemotherapy====
*Cladribine (Leustatin) 0.13 mg/kg IV over 2 hours once per day on days 1 to 5
====Supportive therapy====
*Clemastine (Tavist) 1 to 2 mg IV once per day on days 1 to 5, prior to cladribine
*Dexamethasone (Decadron) 5 mg IV once per day on days 1 to 5, prior to cladribine
*Fluconazole (Diflucan) (dose not specified)
* Co-trimaxazole (dose not specified)
*Valacyclovir (Valtrex) (dose not specified) "in some patients"
4- to 6-week cycle for 6 cycles
===Regimen variant #2, 0.14 mg/kg===
Study 	Dates of enrollment	Evidence
Barete et al. 2015	2001-03 to 2010-06 	Retrospective
====Chemotherapy====
*Cladribine (Leustatin) 0.14 mg/kg SC or IV over 2 hours once per day on days 1 to 5
4- to 12-week cycle for 1 to 6 cycles
===Regimen variant #3, 5 mg/m2===
Study 	Dates of enrollment	Evidence
Lim et al. 2009	1976-01 to 2007-10 	Retrospective
Note: This was a retrospective series; a range of weight-based dosing was also reported.
====Chemotherapy====
*Cladribine (Leustatin) 5 mg/m2 IV over 2 hours once per day on days 1 to 5
Median number of treatment cycles was 3 (range 1 to 9)
===References===
# Kluin-Nelemans HC, Oldhoff JM, Van Doormaal JJ, Van 't Wout JW, Verhoef G, Gerrits WB, van Dobbenburgh OA, Pasmans SG, Fijnheer R. Cladribine therapy for systemic mastocytosis. Blood. 2003 Dec 15;102(13):4270-6. Epub 2003 Aug 21. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 
# Retrospective: Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. link to original article EuroPMC
# Retrospective: Barete S, Lortholary O, Damaj G, Hirsch I, Chandesris MO, Elie C, Hamidou M, Durieu I, Suarez F, Grosbois B, Limal N, Gyan E, Larroche C, Guillet G, Kahn JE, Casassus P, Amazzough K, Coignard-Biehler H, Georgin-Lavialle S, Lhermitte L, Fraitag S, Canioni D, Dubreuil P, Hermine O. Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis. Blood. 2015 Aug 20;126(8):1009-16. Epub 2015 May 22. link to original article EuroPMC
==Dasatinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Verstovsek et al. 2008	Not reported 	Phase 2
Note: Only 9 of 67 patients studied had ASM; 18 has ISM and 6 had SM-AHNMD.
====Targeted therapy====
*Dasatinib (Sprycel) 70 mg PO twice per day on days 1 to 28
**Alternative dosing: 140 mg PO once per day
====Supportive therapy====
*Hematopoietic growth factors at investigator discretion
28-day cycles
===References===
# Verstovsek S, Tefferi A, Cortes J, O'Brien S, Garcia-Manero G, Pardanani A, Akin C, Faderl S, Manshouri T, Thomas D, Kantarjian H. Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis. Clin Cancer Res. 2008 Jun 15;14(12):3906-15. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==Imatinib monotherapy==
===Regimen variant #1, 100 mg/day===
Study 	Dates of enrollment 	Evidence
Pardanani et al. 2003	2001-08-13 to 2003-03-04	Phase 2, fewer than 20 pts reported
====Targeted therapy====
*Imatinib (Gleevec) 100 mg PO once per day
Continued indefinitely
===Regimen variant #2, 400 mg/day x 6 mo===
Study 	Dates of enrollment	Evidence
Droogendijk et al. 2006	2003-02 to 2004-11 	Phase 2, fewer than 20 pts reported
====Targeted therapy====
*Imatinib (Gleevec) 400 mg PO once per day
====Supportive therapy====
*Prednisone (Sterapred) 15 mg PO twice per day on days 1 to 14
6-month course
===Regimen variant #3, 400 mg/day indefinitely===
Study 	Dates of enrollment 	Evidence
Pardanani et al. 2003	2001-08-13 to 2003-03-04	Phase 2, fewer than 20 pts reported
====Targeted therapy====
*Imatinib (Gleevec) 400 mg PO once per day
Continued indefinitely
===Regimen variant #4, 400 mg/day with dose escalation===
Study 	Dates of enrollment	Evidence
Vega-Ruiz et al. 2009	2003-03 to 2005-05 	Phase 2
====Targeted therapy====
*Imatinib (Gleevec) as follows:
**Cycle 1: 400 mg PO once per day
**Cycle 2: 600 mg PO once per day
**Cycle 3 onwards: 800 mg PO once per day
====Supportive therapy====
*Hematopoietic growth factors at investigator discretion
Monthly cycles
===References===
# Pardanani A, Elliott M, Reeder T, Li CY, Baxter EJ, Cross NC, Tefferi A. Imatinib for systemic mast-cell disease. Lancet. 2003 Aug 16;362(9383):535-6. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, Oranje AP, van de Loosdrecht AA, van Daele PL. Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer. 2006 Jul 15;107(2):345-51. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Retrospective: Pagano L, Valentini CG, Caira M, Rondoni M, Van Lint MT, Candoni A, Allione B, Cattaneo C, Marbello L, Caramatti C, Pogliani EM, Iannitto E, Giona F, Ferrara F, Invernizzi R, Fanci R, Lunghi M, Fianchi L, Sanpaolo G, Stefani PM, Pulsoni A, Martinelli G, Leone G, Musto P. Advanced mast cell disease: an Italian Hematological Multicenter experience. Int J Hematol. 2008 Dec;88(5):483-8. Epub 2008 Nov 26. link to original article EuroPMC 
# Vega-Ruiz A, Cortes JE, Sever M, Manshouri T, Quintás-Cardama A, Luthra R, Kantarjian HM, Verstovsek S. Phase II study of imatinib mesylate as therapy for patients with systemic mastocytosis. Leuk Res. 2009 Nov;33(11):1481-4. Epub 2009 Feb 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
# Retrospective: Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. link to original article EuroPMC
==Interferon alfa-2b monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Casassus et al. 2002	1994-04 to 1997-02 	Phase 2
Note: Doses were escalated based on tolerance.
====Immunotherapy====
*Interferon alfa-2b (Intron-A) as follows:
**Week 1: 1,000,000 units SC once per day
**Week 2: 3,000,000 units SC once per day
**Weeks 3 & 4: 3,000,000 units/m2 SC once per day
**Week 5 onwards: 5,000,000 units/m2 SC once per day
6-month course, continued at physician's and patient's discretion
===References===
# Casassus P, Caillat-Vigneron N, Martin A, Simon J, Gallais V, Beaudry P, Eclache V, Laroche L, Lortholary P, Raphaël M, Guillevin L, Lortholary O. Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol. 2002 Dec;119(4):1090-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Retrospective: Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. link to original article EuroPMC
==Midostaurin monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Efficacy
Gotlib et al. 2016 (CPKC412D2201)	2009-2012 	Phase 2 (RT)	ORR: 60% (95% CI 49 to 70)
Chandesris et al. 2016 (CEREMAST)	2012-2015 	Phase 2 (RT)	
Note: CPKC412D2201 included untreated and previously untreated patients.
====Targeted therapy====
*Midostaurin (Rydapt) 100 mg PO twice per day on days 1 to 28
28-day cycles
===References===
# CPKC412D2201: Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. link to original article dosing details in manuscript have been reviewed by our editors link to supplementary appendix EuroPMC NCT00233454
# CEREMAST: Chandesris MO, Damaj G, Canioni D, Brouzes C, Lhermitte L, Hanssens K, Frenzel L, Cherquaoui Z, Durieu I, Durupt S, Gyan E, Beyne-Rauzy O, Launay D, Faure C, Hamidou M, Besnard S, Diouf M, Schiffmann A, Niault M, Jeandel PY, Ranta D, Gressin R, Chantepie S, Barete S, Dubreuil P, Bourget P, Lortholary O, Hermine O; CEREMAST Study Group. Midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2605-7. link to original article EuroPMC
==Nilotinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Kantarjian et al. 2006 (A2101)	2004-2005 	Phase 1/2
====Targeted therapy====
*Nilotinib (Tasigna) 400 mg PO twice per day on days 1 to 28
28-day cycles
===References===
# A2101: Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 Jun 15;354(24):2542-51. link to original article EuroPMC NCT00109707
## Subgroup analysis: Hochhaus A, Baccarani M, Giles FJ, le Coutre PD, Müller MC, Reiter A, Santanastasio H, Leung M, Novick S, Kantarjian HM. Nilotinib in patients with systemic mastocytosis: analysis of the phase 2, open-label, single-arm nilotinib registration study. J Cancer Res Clin Oncol. 2015 Nov;141(11):2047-60. Epub 2015 May 23. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
=Response criteria=
==IWG-MRT & ECNM consensus response criteria (2013)==
# Gotlib J, Pardanani A, Akin C, Reiter A, George T, Hermine O, Kluin-Nelemans H, Hartmann K, Sperr WR, Brockow K, Schwartz LB, Orfao A, Deangelo DJ, Arock M, Sotlar K, Horny HP, Metcalfe DD, Escribano L, Verstovsek S, Tefferi A, Valent P. International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis. Blood. 2013 Mar 28;121(13):2393-401. Epub 2013 Jan 16. link to original article link to PMC article EuroPMC
Category:Systemic mastocytosis regimens
Category:Disease-specific pages
Category:Myeloproliferative neoplasms