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

Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance. (PubMed, Pharmaceutics) - "Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents-such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib-have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs...Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options,..."

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

Present management of gastrointestinal stromal tumors. (PubMed, Klin Onkol) - "In advanced or metastatic disease, standard care involves sequential treatment with tyrosine kinase inhibitors, including imatinib, sunitinib, and regorafenib. The expanding range of targeted therapies, such as avapritinib for the PDGFRA D842V mutation, underscores the importance of molecular profiling in guiding optimal treatment strategies. This review aims to summarize current knowledge on the diagnosis and treatment of GIST, with a focus on the role of molecular-genetic profiling, the therapeutic value of individual tyrosine kinase inhibitors, and emerging options for advanced disease, with particular emphasis on ripretinib."

Journal • Review • Chronic Myeloid Leukemia • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Hematological Malignancies • Leukemia • Oncology • Sarcoma • PDGFRA

Avapritinib and Bone Health in Indolent Systemic Mastocytosis: Learnings from the PIONEER Trial (ASBMR 2025) - P2 | No abstract available

Avapritinib Durably Improves Cutaneous Involvement of Indolent Systemic Mastocytosis in Patients Treated in the PIONEER Study (EADV 2025) - No abstract available

Clinical • Dermatology

Avapritinib improves symptoms and quality of life in indolent systemic mastocytosis: 6-month real-world outcomes from the AVATAR study (EADV 2025) - No abstract available

Clinical • HEOR • Real-world • Real-world evidence • Cardiovascular • Dermatology • Dermatopathology • Immunology • Urticaria

Avapritinib Durably Improves Cutaneous Involvement of Indolent Systemic Mastocytosis in Patients Treated in the PIONEER Study (EADV 2025) - No abstract available

Clinical

A Rare Case of Acute Aleukemic Mast Cell Leukemia With Osteoblastic Lesions in the Appendicular Skeleton (SOHO 2025) - "We described here a very rare case of aleukemic MCL with diffuse osteoblastic metastatic bone lesions involving axial and appendicular skeleton. With this case, we would like to report that MCL is a malignancy that can present with both osteolytic and osteoblastic bone lesions and stress the importance of bone biopsy in suspected cases of MCL. The mainstay of management of MCL includes targeted chemotherapies, midostaurin or avapritinib, and supportive measures."

Clinical • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology • ANPEP • CD33 • CD4 • KIT

Favorable Benefit-Risk Profile of Avapritinib in Indolent Systemic Mastocytosis Is Maintained After 3 Years of Therapy: Longer-Term Analysis of the PIONEER Study (SOHO 2025) - P2 | "Longer follow-up of patients with ISM in the PIONEER trial, including some on avapritinib for up to 5 years, demonstrates that prolonged avapritinib therapy continues to be effective and generally well tolerated. These data support a favorable benefit-risk profile of avapritinib as a chronic treatment for adult patients with ISM."

Oncology

More Than Just a Gut Feeling: Unmasking Systemic Mastocytosis Behind Chronic GI Symptoms (ACG 2025) - "These findings fulfilled both the major and minor diagnostic criteria for systemic mastocytosis, specifically the indolent variant.After trials with multiple medications, the patient's symptoms have been controlled with fexofenadine, montelukast, and famotidine. Other medications included Cromolyn, which was discontinued due to poor adherence, and a trial drug, Avapritinib, which was stopped due to lower extremity edema and weight gain. This case illustrates the diagnostic and therapeutic challenges of GI involvement in systemic mastocytosis...A low-histamine diet, escalated antihistamine therapy, and consideration of advanced therapies may also provide symptomatic relief and improve quality of life.Figure: Esophagogastroduodenoscopy (EGD) revealed diffuse moderate inflammation in the second portion of the duodenum, charactherized by mucosal congestion, erythema, and nodularity. Figure: Colonoscopy revealed diffuse moderate inflammation in the proximal transverse..."

Barrett Esophagus • Cardiovascular • Celiac Disease • Dermatology • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Hypertension • Immunology • Inflammation • Osteoporosis • Rare Diseases • Rheumatology • KIT

Innovative Therapeutic Approaches in Systemic Mastocytosis: an Updated Review. (PubMed, Maedica (Bucur)) - "The approval of tyrosine kinase inhibitors (TKIs), particularly midostaurin and avapritinib, has provided new therapeutic options for patients with advanced SM, demonstrating significant improvements in overall survival (OS) and symptom control. The present review provides an updated overview of the evolving therapeutic landscape of SM, emphasizing recent clinical trial data, novel targeted therapies and emerging treatment paradigms. We discuss the implications of this progress on patient outcomes and future directions for personalized medicine in SM."

Journal • Transplantation

The evaluation, management, and future of indolent systemic mastocytosis. (PubMed, Ann Hematol) - "Furthermore, management strategies start with symptomatic support and can include targeted KIT inhibition, such as avapritinib, for patients with refractory disease...While many patients have stable disease, a subset may experience persistent morbidity or disease progression. Future directions include improving early recognition, validating biomarkers for monitoring and therapeutic response, and evaluating investigational therapies aimed at modifying disease course."

Journal • Review • Hematological Disorders • Hematological Malignancies • Oncology

Tyrosine Kinase Inhibitors for the Treatment of Mast Cell Diseases: Review and Update. (PubMed, J Investig Allergol Clin Immunol) - "TKIs represent a major advance in the management of MCDs, with more patients being able to benefit from a treatment that addresses pathophysiology. We review the main TKIs currently available for SM, their indications, and their safety and effectiveness."

Journal • Review • Bone Marrow Transplantation • Transplantation • KIT

Avapritinib versus midostaurin or cladribine in advanced systemic mastocytosis: A retrospective real-world external control study. (PubMed, Leuk Res) - P1, P2 | "Results were similar in treatment-naïve (1 L) and previously treated (2 L+) patients; there was improved OS in 1 L avapritinib vs. 1 L midostaurin patients (HR: 0.14 [0.05, 0.42]; p < 0.001) and in 2 L+ avapritinib vs. 2 L+ cladribine patients (0.34 [0.16, 0.71]; p = 0.004). Together, we show that avapritinib treatment resulted in significantly improved OS, longer DOT, and greater reduction in serum tryptase levels compared to midostaurin or cladribine in real-world clinical practice."

Journal • Real-world evidence • Retrospective data

Press Release: Sanofi completes acquisition of Blueprint Medicines (Sanofi Press Release) - "Sanofi today announces the completion of its acquisition of Blueprint Medicines Corporation (Blueprint), adding to its portfolio a commercialized medicine, a promising pipeline, and the expertise of a company specializing in systemic mastocytosis (SM), a rare immunological disease, and other KIT-driven diseases....The acquisition includes a rare immunology disease medicine, Ayvakit/Ayvakyt (avapritinib), approved in the US and EU....The acquisition also includes elenestinib, a next-generation medicine for SM that is a potent and highly selective KIT D816V inhibitor with limited central nervous system penetration....Sanofi also acquired BLU-808, an investigational oral, highly potent and selective wild-type KIT inhibitor."

M&A • Aggressive Systemic Mastocytosis • Immunology

Avapritinib for systemic mastocytosis with an associated myelodysplastic/myeloproliferative neoplasm: a case report and literature review (PubMed, Zhonghua Xue Ye Xue Za Zhi) - "Although avapritinib, a novel targeted therapy, has significantly improved outcomes for SM, the efficacy of treatment for the associated hematologic neoplasm in patients with SM-AHN may be the primary determinant of long-term overall survival and progression-free survival. This report includes a review of relevant literature to provide insights into the clinical diagnosis and management of this rare entity."

Journal • Review • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

Integrating a Rare Disease into Practice: Development of a Toolkit for Systemic Mastocytosis. (PubMed, J Adv Pract Oncol) - "The emergence of targeted therapies, such as avapritinib for both advanced and indolent SM, has further highlighted the need for AP education on novel disease mechanisms and treatment strategies. This project demonstrates a replicable model for developing educational and clinical resources to support APs in managing rare diseases and improving patient-centered care."

Journal • Hematological Disorders • Oncology • Rare Diseases

Management of indolent mastocytosis and mast cell activation syndrome: A clinical yardstick. (PubMed, Ann Allergy Asthma Immunol) - "Unfortunately, there is some lack of guidance on how best to utilize these therapies. This yardstick aims to provide the clinician with a review of available therapies to treat mast cell activation syndrome and indolent systemic mastocytosis and an evidence-based expert opinion approach regarding how best to utilize these therapies."

Journal

Avapritinib monotherapy induces rapid and deep remission of heavily treated, KIT D816H-mutated t(8;21) acute myeloid leukemia, a case report and literature review. (PubMed, Ann Hematol) - "Acute myeloid leukemia (AML) with t(8;21) is a subset of core binding factor AML and is considered to be favorable risk disease in patients receiving intensive cytarabine based chemotherapy. We present a case of a patient with extensively treated KIT D816H-mutated t(8;21) AML who experienced relapse after an allogeneic hematopoietic stem cell transplant and achieved a deep remission rapidly with avapritinib monotherapy. This case highlights the potential role of avapritinib as a targeted therapy for relapsed t(8;21) AML with KIT mutations, warranting further clinical investigation."

Journal • Monotherapy • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Absolute Configuration and Chiroptical Properties of Flexible Drug Avapritinib. (PubMed, Pharmaceuticals (Basel)) - "Biological evaluation revealed (S)-(-)-avapritinib exhibited superior c-KIT D816V inhibitory activity compared to its (R)-(+)-counterpart, a finding corroborated by molecular docking studies elucidating their differential target interactions. This study advances avapritinib stereochemical understanding and establishes a definitive protocol for its absolute configuration assignment, serving as a paradigm for flexible chiral drug characterization."

Journal • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

A New Treatment of Newly Diagnosed KIT Mutation CBF-Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=78 | Recruiting | Sponsor: The First Affiliated Hospital of Soochow University

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

BLOOD-BASED PROTEOMICS FOR DEEPER INSIGHTS INTO INDOLENT SYSTEMIC MASTOCYTOSIS: THE PIONEER TRIAL EXPERIENCE (EHA 2025) - P2 | "To this end, we conducted high throughput profiling of the inflammatory plasma proteome across the large and well-characterized cohort of patients enrolled in PIONEER (NCT03731260), a randomized, double-blind study which that led to the approval of avapritinib, a potent and selective KIT D816V inhibitor, for the treatment of ISM. The Olink® Explore 384 Inflammation (Uppsala, Sweden) protein panel measured 363 soluble proteins in plasma samples from 168 patients with ISM enrolled in PIONEER and 39 age-matched healthy donors... Plasma protein analysis provides a new tool to understand and characterize ISM. Patients with ISM have many alterations in the plasma proteome compared to healthy individuals, highlighting the immune dysregulation seen with this disease. A number of altered proteins have been identified in patients with ISM which could aid in future understanding of the disease and therapeutic targets for its treatment."

Inflammation • Pain • Pruritus • CCL23 • CD48 • CXADR • FABP1 • IL32 • IL4R • IL6 • ITGA1 • TPSAB1

THERAPEUTIC STRATEGIES TARGETING SRSF2 AND KIT MUTATIONS IN SYSTEMIC MASTOCYTOSIS (EHA 2025) - "The efficacy of KIT TKIs midostaurin and avapritinib, and the synergistic effects of spliceosome inhibitors MS023, RKI-1447, and CTX-712 were also evaluated. Our findings suggest that combining KIT TKIs with spliceosome inhibitors represents a promising therapeutic approach for SM. The study highlights the role of SRSF2 and KIT mutations in driving MC malignancy and emphasizes the potential of targeting the spliceosome machinery to overcome drug resistance, potentially improving treatment outcomes for advanced SM."

Oncology • KIT • SRSF2 • STAT5

SOLUBLE ST2 AS A POTENTIAL BIOMARKER AND THERAPEUTIC TARGET IN SYSTEMIC MASTOCYTOSIS (EHA 2025) - "Over 90% of patients with mastocytosis bear an activating mutation in the KIT gene at codon 816 (most commonly KIT D816V), which leads to autonomous MC proliferation.Although treatment options for patients with mastocytosis have increased in recent years, especially with the approval of the KIT-targeting tyrosine kinase inhibitors midostaurin and avapritinib, many patients are still lacking an adequate response, and additional therapies are needed. Taken together, our study shows that serum ST2 levels, particularly the soluble isoform, are significantly increased in SM patients compared to healthy controls, especially in advSM patients. This suggests that ST2 may play a role in the pathophysiology of SM and could potentially serve as a biomarker of disease severity as well as a therapeutic target in SM."

Biomarker • IO biomarker • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • IL33 • IL6 • PD-L1 • TSLP

EXPRESSION OF KIT D814V IN MURINE HEMATOPOIETIC STEM CELLS RESULTS IN AN ADVANCED SYSTEMIC MASTOCYTOSIS PHENOTYPE WITH ASSOCIATED MYELOID NEOPLASM (EHA 2025) - "Kit D814V expression in hematopoietic stem cells (HSC) was obtained by tamoxifen-induced Scl-Cre-mediated recombination. In the present study, we show that expression of Kit D814V in the HSC compartment leads to a phenotype closely resembling human systemic mastocytosis with associated hematologic neoplasia, specifically myeloid neoplasia. We also demonstrate that this phenotype can be corrected by treatment with the KIT inhibitor avapritinib. Thus, this novel mouse line represents an invaluable tool for elucidating molecular pathogenetic mechanisms and testing novel therapeutic targets in mastocytosis."

IO biomarker • Metastases • Preclinical • Hematological Malignancies • Hepatology • Oncology • CCL11 • CCL2 • CCL22 • CXCL12 • CXCL9 • IL10 • IL1B • KIT • PD-L1 • PD-L2 • STAT5 • STAT5AWqe • TNFA

HIGH ACCURACY OF PERIPHERAL BLOOD TESTING AND MACHINE LEARNING-DERIVED PREDICITIVE MODELS TO DISTINGUISH ADVANCED FROM INDOLENT SYSTEMIC MASTOCYTOSIS: ANALYSIS OF AVAPRITINIB AND ELENESTINIB TRIAL DATA (EHA 2025) - P1, P2, P2/3 | "We have successfully created and validated two predictive models that can distinguish AdvSM from ISM with a high degree of accuracy. Their accuracy, when tested across multiple independent patient cohorts, highlights the expected broad applicability of these models in a variety of clinical practice settings."

Machine learning • Metastases • Anemia • Hematological Disorders • Oncology • Thrombocytopenia