Systemic mastocytosis
Section editor | |
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Sanjay R. Mohan, MD, MSCI Vanderbilt University Nashville, TN |
Note: most published trials in this area are for "advanced systemic mastocytosis", which includes more than one WHO category. See individual regimens for details.
7 regimens on this page
12 variants on this page
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Guidelines
NCCN
All lines of therapy
Avapritinib monotherapy
Regimen
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) |
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 contains dosing details in abstract PubMed 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 contains dosing details in manuscript PubMed NCT03580655
- PIONEER: NCT03731260
Cladribine monotherapy
Regimen variant #1, 0.13 mg/kg
Study | Evidence |
---|---|
Kluin-Nelemans et al. 2003 | 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 | Evidence |
---|---|
Barete et al. 2015 | 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 | Evidence |
---|---|
Lim et al. 2009 | Retrospective |
Note: This is 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 contains dosing details in manuscript PubMed
- 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 PubMed
- 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 PubMed
Dasatinib monotherapy
Regimen
Study | Evidence |
---|---|
Verstovsek et al. 2008 | 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
- 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 contains dosing details in manuscript link to PMC article PubMed
Imatinib monotherapy
Regimen variant #1, 100 mg/day
Study | Evidence |
---|---|
Pardanani et al. 2003 | Phase 2, fewer than 20 pts reported |
Regimen variant #2, 400 mg/day x 6 mo
Study | Evidence |
---|---|
Droogendijk et al. 2006 | 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 | Evidence |
---|---|
Pardanani et al. 2003 | Phase 2, fewer than 20 pts reported |
Regimen variant #4, 400 mg/day with dose escalation
Study | Evidence |
---|---|
Vega-Ruiz et al. 2009 | 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 contains dosing details in abstract PubMed
- 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 contains dosing details in manuscript PubMed
- 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 PubMed
- 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 contains dosing details in manuscript link to PMC article PubMed
- 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 PubMed
Interferon alfa-2b monotherapy
Regimen
Study | Evidence |
---|---|
Casassus et al. 2002 | 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 contains dosing details in manuscript PubMed
- 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 PubMed
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.
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 contains dosing details in manuscript link to supplementary appendix PubMed 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 PubMed
Nilotinib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Kantarjian et al. 2006 (A2101) | 2004-2005 | Phase 1/2 |
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 PubMed 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 contains dosing details in manuscript link to PMC article PubMed
Placebo
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lortholary et al. 2017 (AB06006) | 2009-2015 | Phase 3 (C) | Masitinib | Inferior cumulative response |
No active antineoplastic treatment.
References
- AB06006: Lortholary O, Chandesris MO, Bulai Livideanu C, Paul C, Guillet G, Jassem E, Niedoszytko M, Barete S, Verstovsek S, Grattan C, Damaj G, Canioni D, Fraitag S, Lhermitte L, Georgin Lavialle S, Frenzel L, Afrin LB, Hanssens K, Agopian J, Gaillard R, Kinet JP, Auclair C, Mansfield C, Moussy A, Dubreuil P, Hermine O. Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study. Lancet. 2017 Feb 11;389(10069):612-620. Epub 2017 Jan 6. link to original article link to PMC article PubMed NCT00814073
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 PubMed