Ayvakit (avapritinib) / CStone Pharma, Sanofi - LARVOL DELTA

Efficacy and safety of avapritinib in advanced systemic mastocytosis: 4-year follow-up of the PATHFINDER study. (PubMed, Blood Adv) - P2 | "Eleven (10%) patients experienced TEAEs leading to death, of which 1 was deemed related to avapritinib by the principal investigator. With 4-year follow-up, avapritinib-treated patients with AdvSM experienced deep and durable responses and a favorable benefit-risk profile."

Journal • Hematological Disorders • Hematological Malignancies • Oncology • Thrombocytopenia • KIT

Case report: A case of mast cell leukemia treated with avapritinib: from diagnostic challenge to transplantation. (PubMed, Front Oncol) - "Here, we report a case of a 66-year-old woman affected by MCL, highlighting clinical features, diagnostic challenges and complexity, and our treatment choices. Furthermore, we review current literature data and emerging therapeutic approaches, emphasizing the importance of greater clinical awareness and comprehensive multidisciplinary approach to correctly diagnose and treat this condition in order to improve patient outcomes in this challenging disease."

Journal • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology • Transplantation

Mice Expressing KITD814V In The Mast Cell Lineage Show a Systemic Mastocytosis Phenotype with Skin Lesions That Can Be Reversed By Treatment With Specific Tyrosine Kinase Inhibitors (AAAAI 2026) - "Expansion of MC resulted also in elevated serum levels of Mcpt1 and markedly reduced body weight. Olink analysis Conclusions Mctp5-Cre KITD814V mice present an indolent systemic mastocytosis phenotype, which is corrected by treatment with the tyrosine kinase inhibitor avapritinib, suggesting its relevance as a preclinical model."

Preclinical

Initiation of Treatment with FDA-Approved Avapritinib in a Cohort of Patients with Indolent Systemic Mastocytosis: Practical Experience and One Year Follow-up (AAAAI 2026) - "Side effects were minimal and included headache in two Conclusions Avapritinib was well tolerated and led to significant reductions in symptoms and mast cell burden in patients with ISM. These findings support its use as a first-line therapy in KIT D816V-positive ISM with high mast cell burden and mediator-driven symptoms."

Clinical

Real-World Experience of Patients with Indolent Systemic Mastocytosis Treated with Avapritinib in a Community Oncology Setting (AAAAI 2026) - "Median time from diagnosis to treatment was 17.4 months. Patients reported an average of 6.1 symptoms at treatment initiation; fatigue (77.8%), skin rash (83.3%), and nausea/vomiting Conclusions Avapritinib was well-tolerated and led to rapid symptom improvement in patients with ISM in community practice, supporting its real-world clinical utility."

Clinical • Real-world • Real-world evidence • Dermatology

Long-Term Bone Health Outcomes in Patients Treated with Avapritinib for Indolent Systemic Mastocytosis: Findings from the PIONEER study (AAAAI 2026) - P2 | "Mean (SD) percent increase in lumbar spine BMD were: Year 1, 1.66% (5.57%), n=59; Year 3, 4.05% (5.78%), n=26. Conclusions Long-term avapritinib was associated with improvements in lumbar spine BMD and PINP, supporting further research with disease-modifying therapy on bone health in ISM."

Clinical • HEOR • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology • TRAP

A Systematic Literature Review of Avapritinib Outcomes in Patients with Indolent Systemic Mastocytosis (AAAAI 2026) - P2 | "Of these, 16 studies reported outcomes assessed during the PIONEER clinical trial (NCT03731260), and 1 study assessed the impact of avapritinib on disease control and QoL for patients with ISM in a real-world setting. Results from studies from the PIONEER trial showcase avapritinib's disease-modifying effects on ISM, including Conclusions This SLR provides the most current and comprehensive compilation of outcomes data for patients with ISM treated with avapritinib which can inform evidence-based clinical decision-making for this population."

Clinical • Review

Avapritinib Durably Improves Gastrointestinal Symptoms of Indolent Systemic Mastocytosis: Long-Term Outcomes From the PIONEER Study (AAAAI 2026) - "Cromolyn sodium and antihistamine use was also reduced. These clinically meaningful findings, and consistently well-tolerated safety profile, support long-term avapritinib use for ISM-related symptom reduction."

KIT

Avapritinib continues to demonstrate durable symptom control with a well-tolerated safety profile: Long-term outcomes from PIONEER (AAAAI 2026) - P2 | "Conclusions At ∼3.5 years, avapritinib continues to demonstrate durable, clinically meaningful improvements in symptoms and QoL with a well-tolerated safety profile at 25 mg and 50 mg QD. Avapritinib shows a favorable benefit-risk profile for chronic use in adult patients with ISM."

Clinical

Gastrointestinal Stromal Tumors: Histopathological Spectrum, Molecular Subtypes, and Implications for Targeted Therapy. (PubMed, Cureus) - "Targeted tyrosine kinase inhibitors (TKIs) have transformed GIST management, with imatinib as the foundational first-line therapy and subsequent agents, sunitinib, regorafenib, avapritinib, and ripretinib, addressing primary or secondary resistance driven by diverse mutational patterns. Emerging therapeutic directions include next-generation kinase inhibitors, heat shock protein inhibitors, immunotherapy, metabolic and epigenetic targeting, and biomarker-driven individualized treatment strategies. This review synthesizes contemporary advances in the histopathological, molecular, and therapeutic landscape of GISTs, emphasizing an integrated diagnostic approach and highlighting ongoing efforts to overcome therapeutic resistance and optimize personalized care."

IO biomarker • Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • ANO1 • BRAF • CD34 • KIT • KRAS • NF1 • NTRK • PDGFRA

Successful treatment of a patient with metastatic gastrointestinal stromal tumor harboring dual KIT exon 9 and 17 mutations with combination of avapritinib, imatinib, and pioglitazone (DKK 2026) - No abstract available

Clinical • Metastases • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Outcomes of novel tyrosine kinase inhibitors in rare GIST subtypes: A clinico-genomic analysis from the Flatiron Health–Foundation Medicine database. (ASCO-GI 2026) - "The efficacy of newer TKIs such as regorafenib, ripretinib, and avapritinib in these populations remains poorly described in real-world settings...Use of regorafenib and ripretinib improved outcomes compared with sunitinib alone in SDH-deficient cases (median OS 22.1 vs. 14.2 months, p = 0.03)... In this real-world, genomically annotated cohort, newer TKIs provided clinically meaningful benefit in rare GIST subtypes, particularly SDH-deficient and KIT/PDGFRA wild-type tumors, though outcomes remained inferior to classical KIT/PDGFRA-mutant GIST. These findings support the integration of comprehensive genomic profiling to optimize sequencing of TKIs beyond imatinib in rare GIST populations."

Genomic analysis • Omic analysis • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KIT • NF1 • PDGFRA

Nemolizumab as an Alternative Therapeutic Option for Indolent Systemic Mastocytosis. (PubMed, Cureus) - "Treatment options are limited when symptoms remain refractory, and avapritinib is contraindicated or declined. We describe the case of a 62-year-old female with an 11-year history of ISM who developed worsening pruritus and urticaria despite extensive conservative and biologic therapies, including topical corticosteroids, hydroxyzine, montelukast, omalizumab, and dupilumab...After 12 doses, she achieved complete resolution of pruritus. This report suggests that nemolizumab may represent a potential therapeutic option for refractory ISM when standard therapies fail or targeted KIT inhibition is not feasible."

Journal • Cardiovascular • Dermatology • Immunology • Pruritus • Urticaria

Circulating tumor DNA (ctDNA) analyses of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor (GIST). (ASCO 2022) - P3 | "Background: The genotype of primary mutations predicts imatinib response in untreated metastatic GIST...Regorafenib showed similar activity regardless of KIT mutational status and the location of KIT mutation... Hybrid capture-based plasma sequencing detects ctDNA in the majority of patients with advanced TKI-resistant GIST, including heterogeneity of KIT mutations. This study is the first to show that ctDNA sequencing correlates with outcomes in pretreated GIST. Identification of ABP (exon13/14) KIT mutations negatively correlates with avapritinib activity."

Circulating tumor DNA • Clinical • P3 data • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

Circulating tumor DNA analysis of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib. (PubMed, Ann Oncol) - P3 | "CtDNA sequencing efficiently detects KIT/PDGFRA mutations and prognosticates outcomes in patients with TKI-resistant GIST treated with avapritinib. ctDNA analysis can be used to monitor disease progression and provide more personalized treatment."

Circulating tumor DNA • Journal • Metastases • P3 data • Stroma • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

The Evolving Role of Second- and Third-Generation Tyrosine Kinase Inhibitors in Gastrointestinal Malignancies: Advances in Targeted Therapy with Sunitinib, Regorafenib, and Avapritinib. (PubMed, J Clin Med) - "While imatinib revolutionized first-line therapy, resistance and specific mutation profiles necessitate subsequent generations of tyrosine kinase inhibitors (TKIs). Second- and third-generation TKIs have transformed the management of advanced GIST, extending survival and offering mutation-specific precision therapy. Ongoing research into resistance mechanisms, combination strategies, and novel inhibitors promises further optimization of patient-centered care."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA

Press release: 2025: strong sales and EPS growth. Continued profitable growth expected in 2026 (The Manila Times) - "Pharma launches increased sales by 49.4%, reaching €1.1 billion, primarily driven by Ayvakit and ALTUVIIIO"

Commercial • Aggressive Systemic Mastocytosis • Hemophilia A

Journal Club: Mastocytosis: across the spectrum: pathobiology, clinical evaluation, and evolving therapies. (PubMed, Eur J Dermatol) - "Midostaurin and avapritinib have reshaped the treatment of AdvSM, while next-generation tyrosine-kinase inhibitors (TKIs) are in clinical trials. Multidisciplinary care is critical, and knowledge gaps remain in paediatric risk stratification, optimal sequencing of therapies, and disease progression assessment. This review highlights recent advances and future priorities for personalized, evidence-based care."

Journal • Review • Pediatrics • Rare Diseases

Ayvakit (mastocytosis) sales were €168 million. (GlobeNewswire) - "Sales were split between the US (€148 million) and Europe (€20 million) with continued growth in the number of patients treated. Sales growth was partly offset by shipping patterns in the US, and an element of price adjustment. In the full year, pro-forma sales reached $725 million, slightly ahead of Blueprint expectations from earlier in the year ($700-720 million). Sanofi does not hold marketing rights in China but receives royalty on sales by CStone Pharmaceuticals."

Sales • Aggressive Systemic Mastocytosis

Case Report: A rare case of synchronous ovarian mixed germ cell tumor and mast cell leukemia in a pediatric patient. (PubMed, Front Oncol) - "Targeted therapy with avapritinib and ruxolitinib was initiated but yielded limited response. Given the consistent co-occurrence of KIT mutations in previously reported similar cases, we propose the recognition of a distinct disease entity: ovarian germ cell tumor/mastocytosis with KIT mutations. This report emphasizes the importance of early genetic profiling and multidisciplinary collaboration in diagnosing and managing rare, genetically unified malignancies in pediatric oncology."

Journal • Cognitive Disorders • Germ Cell Tumors • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology • Ovarian Cancer • Pediatrics • Solid Tumor • Thrombocytopenia • AFP • KIT • NRAS • TP53

Prospective Study of Avapritinib in Patients with Relapsed/Refractory or MRD-Positive Core-Binding Factor Acute Myeloid Leukemia with KIT Mutations (ASH 2024) - "In general, the study results suggest that avapritinib demonstrated good efficacy and safety in patients with CBF-AML harboring KIT gene mutations. These findings may support expanding the indications for this therapy in the treatment of AML."

Clinical • Minimal residual disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Respiratory Diseases • Sarcoma • CBFB • KIT • PDGFRA • RUNX1 • RUNX1T1

THE REVISED MUTATION-ADJUSTED RISK SCORE (MARS-R) FOR PREDICTING OVERALL SURVIVAL IN PATIENTS WITH ADVANCED SYSTEMIC MASTOCYTOSIS TREATED WITH MIDOSTAURIN OR AVAPRITINIB (EHA 2025) - P1, P2 | "The MARS-R captures the continuum of OS risk observed among AdvSM pts, stratifying them into 3 distinct risk categories for treatment with midostaurin or avapritinib. It serves as an important new tool for clinical management of AdvSM patients, particularly regarding treatment maintenance or intensification, such as with allogeneic hematopoietic cell transplantation."

Clinical • Metastases • Aggressive Systemic Mastocytosis • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology • ASXL1 • RUNX1 • SETBP1

Avapritinib As First-Line Therapy in Patients with Advanced Systemic Mastocytosis: Efficacy and Safety from the Pathfinder Clinical Study (ASH 2022) - P1, P2 | "Avapritinib demonstrated a high level of efficacy as the first-line therapy for patients with AdvSM across all disease subtypes with an ORR of 84% and an OS rate of 88% at 2 years. Avapritinib treatment with a 200 mg once-daily starting dose was generally well-tolerated."

Clinical • Anemia • Hematological Disorders • Hematological Malignancies • Immunology • Myeloproliferative Neoplasm • Neutropenia • Oncology • Thrombocytopenia

Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. (PubMed, Nat Med) - P1 | "Avapritinib elicited ≥50% reductions in marrow mast cells and serum tryptase in 92% and 99% of patients, respectively. Avapritinib induced deep and durable responses, including molecular remission of KIT D816V in patients with AdvSM, and was well tolerated at the recommended phase 2 dose of 200 mg daily."

Clinical • Journal • P1 data • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Thrombocytopenia

AVAPRITINIB IN PATIENTS WITH ADVANCED SYSTEMIC MASTOCYTOSIS (ADVSM): EFFICACY AND SAFETY ANALYSIS FROM THE PHASE 2 PATHFINDER STUDY WITH 3-YEAR FOLLOW-UP (EHA 2024) - P1, P2 | "With >3 years of follow-up, patients with AdvSM treated with avapritinib showed continued deep and durableresponses with a favorable benefit-risk profile regardless of AdvSM subtype or prior therapy."

Clinical • Metastases • P2 data • Aggressive Systemic Mastocytosis • Anemia • Eosinophilia • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia