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Superior efficacy of midostaurin over cladribine in advanced systemic mastocytosis: a registry-based analysis : original reports

Purpose - On the basis of data from the German Registry on Disorders of Eosinophils and Mast Cells, we compared the efficacy of midostaurin and cladribine in patients with advanced systemic mastocytosis (AdvSM). - Patients and Methods - Patients with AdvSM (n = 139) were treated with midostaurin onl...

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Main Authors: Lübke, Johannes (Author) , Schwaab, Juliana (Author) , Naumann, Nicole (Author) , Horny, Hans-Peter (Author) , Weiß, Christel (Author) , Metzgeroth, Georgia (Author) , Kreil, Sebastian (Author) , Cross, Nicholas C.P. (Author) , Sotlar, Karl (Author) , Fabarius, Alice (Author) , Hofmann, Wolf-Karsten (Author) , Valent, Peter (Author) , Gotlib, Jason (Author) , Jawhar, Mohamad (Author) , Reiter, Andreas (Author)
Format: Article (Journal)
Language:English
Published: March 02, 2022
In: Journal of clinical oncology
Year: 2022, Volume: 40, Issue: 16, Pages: 1783-1794
ISSN:1527-7755
DOI:10.1200/JCO.21.01849
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1200/JCO.21.01849
Verlag, lizenzpflichtig, Volltext: http://ascopubs.org/doi/10.1200/JCO.21.01849
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Author Notes:Johannes Lübke, Juliana Schwaab, Nicole Naumann, Hans-Peter Horny, Christel Weiß, Georgia Metzgeroth, Sebastian Kreil, Nicholas C.P. Cross, Karl Sotlar, Alice Fabarius, Wolf-Karsten Hofmann, Peter Valent, Jason Gotlib, Mohamad Jawhar, and Andreas Reiter
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Summary:Purpose - On the basis of data from the German Registry on Disorders of Eosinophils and Mast Cells, we compared the efficacy of midostaurin and cladribine in patients with advanced systemic mastocytosis (AdvSM). - Patients and Methods - Patients with AdvSM (n = 139) were treated with midostaurin only (n = 63, 45%), cladribine only (n = 23, 17%), or sequentially (midostaurin-cladribine, n = 30, 57%; cladribine-midostaurin, n = 23, 43%). Prognosis was assessed through the Mutation-Adjusted Risk Score (MARS). Besides the comparison of efficacy between midostaurin and cladribine on response (eg, organ dysfunction, bone marrow mast cell [MC] infiltration, and tryptase), overall survival (OS), and leukemia-free survival, we focused on the impact of treatment on involved non-MC lineages, for example, monocytes or eosinophils, and the KIT D816V expressed allele burden. - Results - Midostaurin only was superior to cladribine only with effects from responses on MC and non-MC lineages conferring on a significantly improved OS (median 4.2 v 1.9 years, P = .033) and leukemia-free survival (2.7 v 1.3 years, P = .044) on the basis of a propensity score-weighted analysis of parameters included in MARS. Midostaurin compensated the inferior efficacy of cladribine in first- and second-line treatment. On midostaurin in any line, response of eosinophilia did not improve its baseline adverse prognostic impact, whereas response of monocytosis proved to be a positive on-treatment parameter. Multivariable analysis allowed to establish three risk categories (low/intermediate/high) through the combination of MARS and the reduction of the KIT D816V expressed allele burden of ≥ 25% at month 6 (median OS not reached v 3.0 years v 1.0 year; P < .001). - Conclusion - In this registry-based analysis, midostaurin revealed superior efficacy over cladribine in patients with AdvSM. In midostaurin-treated patients, the combination of baseline MARS and molecular response provided a compelling three-tier risk categorization (MARSv2.0) for OS.
Item Description:Gesehen am 30.01.2024
Physical Description:Online Resource
ISSN:1527-7755
DOI:10.1200/JCO.21.01849

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