Real-World Efficacy of Midostaurin in Aggressive Systemic Mastocytosis

Szudy‐Szczyrek, Aneta; Bachanek-Mitura, Oliwia; Gromek, Tomasz; Chromik, Karolina; Mital, Andrzej; Szczyrek, Michał; Krupski, Witold; Szumiło, Justyna; Kanduła, Zuzanna; Helbig, Grzegorz; Hus, Marek

doi:10.3390/jcm10051109

Cited by 12 publications

(12 citation statements)

References 36 publications

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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 . 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: 66%

“…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. We used a modified valent response Taken together, the data so far regarding the use of midostaurin in adv-SM support its use as an alternative to cladribine therapy with similar degree of efficacy but significantly different side effect profile.…”

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: 66%

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…A single case report and a small patients series confirmed these results [80,81]. In patients with slow progression, treatment with midostaurin can induce major clinical responses with improvement or disappearance of C-findings, a decrease in MC burden in the BM and other organs, and a reduction in mediator-related symptoms in a significative number of patients, with moderate gastroenteric side effects [11,12,[82][83][84][85][86][87]. Midostaurin may be used both as first-line treatment, especially in MCL patients, as well as salvage therapy in patients progressing after interferon-α, cladribine, or other cytoreductive therapy.…”

Section: Treatmentmentioning

confidence: 65%

Precision Medicine in Systemic Mastocytosis

et al. 2021

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Mastocytosis is a rare hematological neoplasm characterized by the proliferation of abnormal clonal mast cells (MCs) in different cutaneous and extracutaneous organs. Its diagnosis is based on well-defined major and minor criteria, including the pathognomonic dense infiltrate of MCs detected in bone marrow (BM), elevated serum tryptase level, abnormal MCs CD25 expression, and the identification of KIT D816V mutation. The World Health Organization (WHO) classification subdivides mastocytosis into a cutaneous form (CM) and five systemic variants (SM), namely indolent/smoldering (ISM/SSM) and advanced SM (AdvSM) including aggressive SM (ASM), SM associated to hematological neoplasms (SM-AHN), and mast cell leukemia (MCL). More than 80% of patients with SM carry a somatic point mutation of KIT at codon 816, which may be targeted by kinase inhibitors. The presence of additional somatic mutations detected by next generation sequencing analysis may impact prognosis and drive treatment strategy, which ranges from symptomatic drugs in indolent forms to kinase-inhibitors active on KIT. Allogeneic stem cell transplant (SCT) may be considered in selected SM cases. Here, we review the clinical, diagnostic, and therapeutic issues of SM, with special emphasis on the translational implications of SM genetics for a precision medicine approach in clinical practice.

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“…A Polish study reported data on the real-world efficacy of midostaurin on 13 patients with AdvSM. 52 After a median duration of treatment of 9 months (range 1–21), a clinical benefit was detectable in 77% of patients, and half of the patients with measurable organ damage obtained a response. After a median follow-up of 19 months, the authors reported seven patients with ongoing therapy and three patients died of progressive disease.…”

Section: Midostaurinmentioning

confidence: 98%

Treatment of Indolent and Advanced Systemic Mastocytosis

Buonomo

Nucera

Criscuolo³

2022

Mediterr J Hematol Infect Dis

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Management of Indolent and Smoldering SM is focused on preventing anaphylactic reactions, identifying and avoiding symptom triggers. Skin and gastrointestinal symptoms are managed with H1- and H2-antihistamines. When skin symptoms are not adequately controlled, leukotriene antagonists and oral psoralen combined with ultraviolet therapy may be added. Proton pump inhibitors, sodium cromolyn and oral corticosteroids may be added for gastrointestinal symptoms. Patients should be prescribed with self-injectable epinephrine and trained to treat recurrent cardiovascular symptoms or anaphylaxis. Depression and cognitive impairment require a psychiatric evaluation for tailored treatment. Bone involvement is managed with bisphosphonates, and eventually interferon. Omalizumab is effective on all vasomotor symptoms, including anaphylaxis, but not on respiratory, musculoskeletal, and neuropsychiatric symptoms. A cytoreductive treatment is not recommended unless anti-mediator therapy has failed. Venom immunotherapy is mandatory for patients with hymenottera venom allergy. There is not a curative option for patients with Advanced SM. The available therapeutic options include tirosin-kinase inhibitors and cladribine, with variable duration and extent of response. Imatinib mesylate was the first drug approved for SM lacking the cKIT D816V mutation; dasatinib and nilotinib are not effective. Midostaurin is active on both wild type and mutant cKIT D816V while Avapritinib is a selective cKIT D816V inhibitor: they are approved for treatment of Advanced SM. Cladribine is a purine analogue with significant activity against monocytes that were thought to have a common progenitor with mast cells. Allogeneic stem cell transplantation is usually performed in younger selected patients. MASTOCYTOSIS; THERAPY; SKIN INVOLVEMENT, SYSTEMIC MASTOCYTOSIS; TYROSINKINASEINHIBITORS; MIDOSTAURIN.

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Real-World Efficacy of Midostaurin in Aggressive Systemic Mastocytosis

Cited by 12 publications

References 36 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

Precision Medicine in Systemic Mastocytosis

Treatment of Indolent and Advanced Systemic Mastocytosis

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