Cem Akin, MD

Future directions in ISM, including evolving treatment goals, unanswered questions about osteoporosis, anaphylaxis, resistance, curative strategies, and the need to extend advances to pediatric populations.

Use of symptom and quality-of-life tools alongside biomarkers in PIONEER, principles of dose titration from 25 mg to 50 mg, and practical recommendations for longitudinal safety monitoring.

Shared decision-making around initiating targeted therapy, key safety considerations for avapritinib, and core efficacy and safety findings from the 6‑month randomized phase of the PIONEER trial.

Role of patient-reported outcomes in trials and practice, criteria for escalation beyond supportive care, and the paradigm shift introduced by selective KIT D816V inhibition, including avapritinib.

Overview of KIT D816V–driven disease biology in ISM and practical approaches to longitudinal symptom monitoring, including emerging use of the Mastocytosis Control Test.

Introduction to ISM with emphasis on evolving clinical perception, disease heterogeneity, and persistent unmet needs despite conventional symptomatic therapy.

Cogent Biosciences previously submitted an NDA for bezuclastinib at the end of 2025.

Akin discussed how avapritinib continues to demonstrate its benefit in indolent systematic mastocytosis.

Akin discussed updated data on elenestinib from the HARBOR trial in indolent systemic mastocytosis.

A panelist discusses how they have growing confidence in pipeline therapies for indolent systemic mastocytosis based on their experience with the PIONEER trials, particularly noting improvements in patient symptoms and quality of life, while expressing hope for additional data on the drug's effects on bone health and anaphylactic events, and describing other investigational treatments including selective inhibitors and Bruton tyrosine kinase inhibitors currently in clinical trials.

A panelist discusses how they have growing confidence in pipeline therapies for indolent systemic mastocytosis based on their experience with the PIONEER trials, particularly noting improvements in patient symptoms and quality of life, while expressing hope for additional data on the drug's effects on bone health and anaphylactic events, and describing other investigational treatments including selective inhibitors and Bruton tyrosine kinase inhibitors currently in clinical trials.

A panelist discusses how avapritinib provides broad, multi-organ symptom relief in indolent systemic mastocytosis—improving skin, gastrointestinal, and neurocognitive symptoms—leading to significant quality-of-life gains, though its effects on osteoporosis and anaphylaxis remain under investigation.

A panelist discusses how patients with indolent systemic mastocytosis who have high mast cell burdens, inadequate symptom control, and stable tolerance at 25 mg may be ideal candidates for avapritinib dose escalation to 50 mg.

A panelist discusses how the durability and safety of avapritinib over several years support its long-term use in indolent systemic mastocytosis, potentially increasing confidence among community providers to prescribe it beyond specialized centers.

A panelist discusses how appropriate candidates for avapritinib include patients with moderate to severe indolent systemic mastocytosis who remain symptomatic despite standard therapies, while those with low platelet counts, pregnancy, bleeding risks, or certain comorbidities should be excluded through shared decision-making.

A panelist discusses how the three part PIONEER study shows that avapritinib 25 mg (with optional escalation to 50 mg) sustains meaningful symptom and quality of life improvements with a favorable safety profile for up to five years, supporting its FDA approval for indolent systemic mastocytosis.

A panelist discusses how long-term safety and efficacy data are essential for treating indolent systemic mastocytosis, given its chronic nature and the potential need for lifelong therapy, with recent findings supporting the sustained benefits of avapritinib.

A panelist discusses how the current standard of care for indolent systemic mastocytosis involves stepwise symptom management with antihistamines and other antimediator therapies, though treatment challenges include limited efficacy, adverse effects, and the burden of polypharmacy.

A panelist discusses how indolent systemic mastocytosis is driven by a KIT D816V mutation that causes constant mast cell activation, leading to heterogeneous clinical presentations and highlighting the importance of targeted therapies like selective KIT inhibitors.

A panelist discusses how indolent systemic mastocytosis presents with chronic, mast cell–mediated symptoms that significantly reduce quality of life, often persist despite treatment, and may lead to serious complications like anaphylaxis and osteoporosis.