Midostaurin therapy for indolent and smoldering systemic mastocytosis: Retrospective review of Mayo Clinic experience

Farrukh, Faiqa; Gangat, Naseema; Shah, Mithun Vinod; Litzow, Mark R.; Elliott, Michelle A.; Begna, Kebede H.; Hook, C. Christopher; Tefferi, Ayalew; Pardanani, Animesh

doi:10.1002/ajh.26464

Cited by 7 publications

(9 citation statements)

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“…The current retrospective study summarizes our experience with midostaurin therapy in adv‐SM and complements our recent publication on midostaurin therapy in indolent/smoldering SM 13 . Real‐word data on midostaurin therapy in adv‐SM are scarce and limited to a handful of cases 14 .…”

Section: Discussionmentioning

confidence: 68%

“…The current retrospective study summarizes our experience with midostaurin therapy in adv-SM and complements our recent publication on midostaurin therapy in indolent/smoldering SM. 13 Real-word data on midostaurin therapy in adv-SM are scarce and limited to a handful of cases. 14 The current report included 33 patients with ASM (n = 17), SM-AHN (n = 14), and MCL (n = 2) with organopathy documented in 91% of the patients.…”

Section: Discussionmentioning

confidence: 99%

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Midostaurin therapy for advanced systemic mastocytosis: Mayo Clinic experience in 33 consecutive cases

et al. 2022

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We retrospectively examined our experience with midostaurin therapy in 33 consecutive patients (median age 68 years; 58% females) with advanced systemic mastocytosis (adv-SM): aggressive SM (ASM; n = 17), SM associated with another hematologic neoplasm (SM-AHN; n = 14) and mast cell leukemia (MCL; n = 2). KITD816V mutation was detected in 84% of the patients and C findings in 91%. Eleven (33%) patients were previously treated with other cytoreductive drugs, including cladribine (n = 4) and imatinib (n = 3). Median time from diagnosis to initiation of midostaurin therapy was 2.2 months (range 0.3-41). Using modified valent criteria, overall response was 42% (53% ASM, 29% SM-AHN, 50% MCL; p = .22), all classified as being major. Responses included ≥50% reduction in bone marrow mast cells in 40% and normalization of serum tryptase in 29%, of evaluated cases. After a median follow-up of 14.6 months from initiation of midostaurin therapy, 7 (21%) deaths, 1 (3%) leukemic progression, and 18 (55%) treatment discontinuations were documented; median duration of midostaurin treatment was 7.9 months (range 0.5-123) and response duration 21.5 months (range 2.9-123).Most frequent side effect was gastrointestinal (51%) while grade 3/4 neutropenia or thrombocytopenia occurred in 12% of patients. Response to treatment was not predicted by KIT mutation (p = .67) or exposure to prior cytoreductive therapy (p = .44).Median survival was longer in midostaurin responders but not significantly (median 26.5 vs. 16 months; p = .15). Findings from the current study are broadly consistent with previously published clinical trial observations.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Midostaurin therapy for advanced systemic mastocytosis: Mayo Clinic experience in 33 consecutive cases

et al. 2022

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“…Thirteen patients were recruited; in the 19-month median times from midostaurin initiation and last follow-up, 62% and 44% of the patients had improvement in MC-related mediator symptoms and MC skin lesions, respectively. Moreover, clinical responses were associated with a decrease of MCs BM in 4 out of 5 BM-evaluable patients and serum tryptase in 9 out of 11 evaluable patients [67].…”

Section: Midostaurinmentioning

confidence: 94%

“…A retrospective series on midostaurin use in ISM and SSM patients included in the Mayo clinic cohort was recently published [67]. Thirteen patients were recruited; in the 19-month median times from midostaurin initiation and last follow-up, 62% and 44% of the patients had improvement in MC-related mediator symptoms and MC skin lesions, respectively.…”

Section: Midostaurinmentioning

confidence: 99%

“…This study confirmed that midostaurin treatment could lead to a clinical benefit in ISM/SSM patients, but the tolerability was limited by a high incidence of gastrointestinal adverse events which needed dose reduction (nine patients) and/or treatment discontinuation (five patients). These observations raise questions about the use of midostaurin in a long-term period for an indolent disease [67].…”

Section: Midostaurinmentioning

confidence: 99%

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Target Therapies for Systemic Mastocytosis: An Update

et al. 2022

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Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MCs) in extra-cutaneous organs. It could be divided into indolent SM, smoldering SM, SM with an associated hematologic (non-MC lineage) neoplasm, aggressive SM, and mast cell leukemia. SM is generally associated with the presence of a gain-of-function somatic mutation in KIT at codon 816. Clinical features could be related to MC mediator release or to uncontrolled infiltration of MCs in different organs. Whereas indolent forms have a near-normal life expectancy, advanced diseases have a poor prognosis with short survival times. Indolent forms should be considered for symptom-directed therapy, while cytoreductive therapy represents the first-line treatment for advanced diseases. Since the emergence of tyrosine kinase inhibitors (TKIs), KIT inhibition has been an attractive approach. Initial reports showed that only the rare KITD816V negative cases were responsive to first-line TKI imatinib. The development of new TKIs with activity against the KITD816V mutation, such as midostaurin or avapritinib, has changed the management of this disease. This review aims to focus on the available clinical data of therapies for SM and provide insights into possible future therapeutic targets.

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Systemic mastocytosis in adults: 2023 update on diagnosis, risk stratification and management

Pardanani

2023

American J Hematol

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Overview: Systemic mastocytosis (SM) results from clonal proliferation of mast cells (MC) in extracutaneous organs. Diagnosis: The major criterion is presence of multifocal MC clusters in the bone marrow and/or extracutaneous organs. Minor diagnostic criteria include elevated serum tryptase level, MC CD25/CD2/CD30 expression, and presence of activating KIT mutations. Risk Stratification: Establishing SM subtype as per the International Consensus Classification/World Health Organization classification systems is an important first step. Patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, including aggressive SM (ASM), SM with associated myeloid neoplasm (SM-AMN), and mast cell leukemia. Identification of poor-risk mutations (i.e., ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Several risk models are available to help assign prognosis in SM patients. Management: Treatment goals for ISM patients are primarily directed toward anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to reverse disease-related organ dysfunction. Tyrosine kinase inhibitors (TKI) (midostaurin, avapritinib) have changed the treatment landscape in SM. While deep biochemical, histological and molecular responses have been documented with avapritinib treatment, its efficacy as monotherapy against a multimutated AMN disease component in SM-AMN patients remains unclear. Cladribine continues to have a role for MC debulking, whereas interferon-α has a diminishing role in the TKI era. Treatment of SM-AMN primarily targets the AMN component, particularly if an aggressive disease such as acute leukemia is present. Allogeneic stem cell transplant has a role in such patients. Imatinib has a therapeutic role only in the rare patient with an imatinib-sensitive KIT mutation. | DISEASE OVERVIEW AND PATHOGENESISSystemic mastocytosis (SM) results from a clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells (MC) that accumulate in one or more organ systems. 1,2 The sine qua non of mastocytosis is the presence of multifocal clusters of abnormal MC, which in contrast to normal MC are variable in appearance, ranging from round to fusiform variants with long, polar cytoplasmic processes, and may display cytoplasmic hypogranularity with

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Midostaurin therapy for indolent and smoldering systemic mastocytosis: Retrospective review of Mayo Clinic experience

Cited by 7 publications

References 7 publications

Midostaurin therapy for advanced systemic mastocytosis: Mayo Clinic experience in 33 consecutive cases

Midostaurin therapy for advanced systemic mastocytosis: Mayo Clinic experience in 33 consecutive cases

Target Therapies for Systemic Mastocytosis: An Update

Systemic mastocytosis in adults: 2023 update on diagnosis, risk stratification and management

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