Ayvakit (avapritinib) / Blueprint Medicines, CStone Pharma - LARVOL DELTA

Continued symptom and quality of life improvement with favorable safety shown with long-term avapritinib in indolent systemic mastocytosis. (PubMed, J Allergy Clin Immunol Pract) - No abstract available

HEOR • Journal

Real-world clinical characteristics and outcomes of systemic mastocytosis (SM) patients (Pts) in the era of targeted treatments (Txs): A single-center cohort analysis. (ASCO 2025) - "89% ISM pts were on active surveillance (AS) for first line (1L) tx, and 87% were on avapritinib (ava) for 2L tx...With ASM pts, 45% were on ava, 27% AS, and 9.1% each for imatinib, midostaurin (mido) and other for 1L... This real-world study highlights the heterogeneity in SM pts. OS was NR for ISM consistent with prior data. OS for ASM pts was NR; previously OS was reported at 3.5 years."

Clinical • Real-world • Real-world evidence • Aggressive Systemic Mastocytosis • Chronic Myelomonocytic Leukemia • Fatigue • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Multiple Myeloma • Oncology • Pain • Smoldering Multiple Myeloma • KIT

CLINICAL CHARACTERISTICS AND OUTCOMES OF KIT-MUTATED ACUTE MYELOID LEUKEMIA: A RETROSPECTIVE COHORT STUDY OF 67 PATIENTS (EHA 2025) - "Co-mutation patterns were mapped using Maftools, and KIT mutation clearance dynamics were tracked via quantitative PCR (qPCR).Among the 64 evaluable patients, intensive chemotherapy (n = 47) achieved significantly higher CR rates compared to venetoclax-based regimens (n = 17) (85.1% vs. 52.9%, P = 0.007)...Avapritinib-treated patients (n = 9) had comparable EFS (P = 0.21) and OS (P = 0.88), but links to treatment duration and combinations require study... Exon 17 KIT mutations are predictive of inferior EFS in AML patients. Intensive chemotherapy enhances remission rates, while allo-HSCT emerges as a pivotal strategy for improving OS. The high relapse rate observed despite molecular remission underscores the critical need for mutation-specific monitoring and the development of targeted consolidation strategies."

Retrospective data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • ASXL1 • FLT3 • KIT • NRAS

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

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."

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

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

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

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

MODELING ADVANCED SYSTEMIC MASTOCYTOSIS: A NOVEL TRANSGENIC MOUSE LINE RECAPITULATES HUMAN DISEASE AND VALIDATES EFFICACY OF AVAPRITINIB (EHA 2025) - "IgE- and MRGPRX2-mediated anaphylaxis were performed as described using DNP-specific IgE and ciprofloxacin, respectively. Additionally, diseased mice received oral avapritinib (30 mg/kg bodyweight, daily), a tyrosine kinase inhibitor approved for human SM, and were observed for its impact on disease progression and anaphylaxis susceptibility.Tamoxifen-induced Kit+/D814V expression in adult Scl-CreERT; Kit+/D814V mice (n=23) led to a symptomatic disease phenotype closely resembling human AdvSM after a median latency of 139 days... We established and characterized a novel inducible transgenic mouse line, SclCreERT; Kit+/D814V, that faithfully recapitulates key features of AdvSM including SM-AHN of myeloid origin. Treatment experiments with avapritinib, the first-line tyrosine kinase inhibitor therapy for AdvSM, demonstrated that our model is a suitable pre-clinical in vivo platform to evaluate novel therapeutic strategies."

Metastases • Preclinical • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor

SELINEXOR SYNERGISTICALLY PROMOTES THE ANTILEUKEMIA ACTIVITY OF AVAPRITINIB IN ACUTE MYELOID CELLS (AML) WITH AML1-ETO AND KIT MUTATION BY TARGETING PLK1 SIGNALING AND E2F SIGNALING (EHA 2025) - "The combination of avapritinib and selinexor exhibited synergistic effects targeting PLK1-FOXO3 axis and CDK4/6-pRB-E2F-cMYC axis in AML t(8; 21) and with KIT mutation, providing rationale for a clinical trial in the future."

IO biomarker • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Oncology • CCNB1 • CD24 • CDK1 • CDK4 • CXCR4 • KIT • MYC • PLK1 • RNASE2 • XPO1

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 Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology • ASXL1 • RUNX1 • SETBP1

Gastrointestinal Stromal Tumor: Current Approaches and Future Directions in the Treatment of Advanced Disease. (PubMed, Hematol Oncol Clin North Am) - "It covers the role of tyrosine kinase inhibitors (TKIs), specifically imatinib, and further treatment options, such as sunitinib, regorafenib, and ripretinib, as well as avapritinib for platelet-derived growth factor receptor alpha D842V mutations. In addition, this review emphasizes individualized treatment strategies within multidisciplinary expert teams, including surgery and other locoregional therapies, together with the importance of mutation-guided approaches, particularly for wild-type GISTs. Finally, it explores the potential of next-generation KIT inhibitors, combination therapies, and other investigational approaches."

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

Evaluation of the effectiveness and safety of avapritinib in real-world Spanish cases with gastrointestinal stromal tumor and D842V-PDGFRA mutation. (PubMed, Oncologist) - "Avapritinib extends PFS and OS among patients with PDGFRA D842V-mutant GIST in real-world practice, mirroring pivotal trial outcomes. Its substantial activity supports its use as a first-line therapy for this subgroup. The manageable safety profile reinforces avapritinib viability for routine use. Given the rarity of these cases, it is advised to consult sarcoma-expert units."

Journal • Observational data • Real-world evidence • Retrospective data • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor • PDGFRA

Targeted inhibition of PDGFRA with avapritinib, markedly enhances lenvatinib efficacy in hepatocellular carcinoma in vitro and in vivo: clinical implications. (PubMed, J Exp Clin Cancer Res) - "Our findings demonstrate that PDGFRA overexpression mediates lenvatinib resistance in HCC and that targeting PDGFRA with avapritinib, surmounts this resistance. Furthermore, the PTEN/AKT/GSK-3β/β-catenin pathway was implicated in lenvatinib resistance, providing a potential therapeutic strategy for HCC patients displaying lenvatinib resistance. Further clinical studies are warranted to validate these findings and to explore the clinical application of PDGFRA-targeted therapies in HCC treatment."

Journal • Preclinical • Hepatocellular Cancer • Oncology • Solid Tumor • PDGFRA • PTEN

Selecting optimal therapy in systemic mastocytosis: current state and future directions. (PubMed, Expert Opin Pharmacother) - No abstract available

Journal

“A full HTA is recommended to assess the clinical effectiveness and cost effectiveness of avapritinib compared with the current standard of care.” [For indolent systemic mastocytosis] (National Centre for Pharmacoeconomics, Ireland)

HEOR • Hematological Malignancies • Oncology

Blueprint Medicines Reports First Quarter 2025 Results and Raises AYVAKIT/AYVAKYT (avapritinib) Full Year Revenue Guidance (PRNewswire) - "Achieved AYVAKIT net product revenues of $149.4 million for the first quarter of 2025, including $129.4 million in the US and $20 million ex-US, representing 61% percent growth year-over-year....Revenues: Revenues were $149.4 million for the first quarter of 2025, generated by net product sales of AYVAKIT/AYVAKYT. Revenues were $96.1 million in the first quarter of 2024, including $92.5 million of net product revenues from sales of AYVAKIT/AYVAKYT and $3.6 million in collaboration revenues."

Commercial • Sales • Aggressive Systemic Mastocytosis • Gastrointestinal Stromal Tumor • Soft Tissue Sarcoma

(PATHFINDER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis (clinicaltrials.gov) - P2 | N=107 | Completed | Sponsor: Blueprint Medicines Corporation | Active, not recruiting ➔ Completed | Trial completion date: Jan 2026 ➔ Dec 2024 | Trial primary completion date: Jan 2026 ➔ Dec 2024

Trial completion • Trial completion date • Trial primary completion date • Tumor mutational burden • Aggressive Systemic Mastocytosis • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology

Mastocytosis. (PubMed, Nat Rev Dis Primers) - "The preclinical and clinical development of KIT-D816V-targeting drugs, such as midostaurin or avapritinib, mark a milestone in improving management, the quality of life and survival in patients with SM. These agents induce major responses or even remission in people with advanced SM and lead to rapid improvement of mediator-related symptoms and quality of life in symptomatic patients."

Journal • Review • Hematological Malignancies • Oncology • Osteoporosis • Rare Diseases • Rheumatology • Sarcoma • Solid Tumor

TGRX-3544 is a highly potent and mutant-selective degrader of oncogenic KIT with oral activity (AACR 2025) - "The cellular activity of TGRX-3544 against the E11, E17 and E11/E17 mutants was superior to that of all the currently approved KIT inhibitors imatinib, sunitinib, regorafenib, avapritinib and ripretinib. In summary, we have developed a highly mutant-selective, event-driven, scaffold-eliminating KIT degrader with superior cellular potency and in vivo oral activity. The balanced preclinical profile of TGRX-3544 supports its further clinical investigation in KIT-driven malignancies such as GIST and SM."

Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • ABL1 • BCR • EGFR • FLT3 • PDGFRA • STAT5

In melanoma, disruption of the NF1/SPRED1 RAS inactivating complex cooperates with mutant KIT necessitating combined KIT and MEK inhibition to suppress tumor growth (AACR 2025) - "In patient-derived melanoma cell lines with KIT mutations and loss of NF1 or SPRED1, combination treatment with a KIT inhibitor (imatinib or avapritinib) and a MEK inhibitor (trametinib) acted synergistically. Combined KIT and MEK inhibition also reduced tumor growth and prolonged survival of mice xenografted with KIT-mutant melanoma cell lines. Our findings suggest that combination therapy with KIT and MEK inhibitors would be beneficial for melanoma patients with activating KIT mutations and concomitant loss of function NF1/SPRED1 mutations."

Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • KIT • NF1

AVAPRITINIB POST-ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR ADVANCED SYSTEMIC MASTOCYTOSIS: A CASE SERIES (EBMT 2025) - "After induction treatment with cytarabine, cladribine, idarubicin, and venetoclax, partial remission (PR) was achieved pre-alloHSCT...A molecular relapse of AHN was treated with azacitidine, venetoclax, and donor lymphocyte infusions (DLI), restoring and maintaining MRDneg. Ava was continued at 100 mg daily due to grade 3 thrombocytopenia.Patient 3 progressed from indolent systemic mastocytosis (ISM) to smoldering systemic mastocytosis (SSM) and ultimately to MCL...Initial treatments, including midostaurin and cladribine, reduced mast cell infiltration pre-alloHSCT but failed to achieve remission... Ava in the post-transplant setting was highly effective in all patients, with durable responses, including converting persistent disease to CR or MRDneg. The safety profile was favorable, with only one grade 3 thrombocytopenia resolved by dose reduction. Compared to the literature, these outcomes suggest prolonged OS."

Clinical • Metastases • Aggressive Systemic Mastocytosis • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • Transplantation

OVERALL SURVIVAL AND DURATION OF TREATMENT IN PATIENTS WITH ADVANCED SYSTEMIC MASTOCYTOSIS RECEIVING AVAPRITINIB VERSUS MIDOSTAURIN OR BEST AVAILABLE THERAPY IN A REAL-WORLD SETTING (EBMT 2025) - P=N/A, P2 | "In IPTW-weighted Cox analysis, DOT was significantly longer in avapritinib versus midostaurin patients (HR [95% CI]: 0.37 [0.19, 0.70]; p=0.002).2L+ analysis: The avapritinib cohort included 67 patients, and the BAT cohort included 73 patients, contributing data on 104 lines of therapy (LOTs). Agent-level information was available for 89 LOTs in the BAT cohort, and common 2L+ agents were midostaurin (46.1%), cladribine (32.6%), and hydroxyurea (7.9%)... This study supports the use of avapritinib as 1L treatment for AdvSM, demonstrating significant OS and DOT benefits compared with 1L midostaurin. These results affirm that AdvSM patients with prior treatment experienced significantly improved OS and DOT on avapritinib compared to patients treated with BAT in the real world. Clinical Trial Registry: N/A"

Clinical • Metastases • Real-world • Real-world evidence • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

OVERALL SURVIVAL AND DURATION OF TREATMENT IN PATIENTS WITH ADVANCED SYSTEMIC MASTOCYTOSIS RECEIVING AVAPRITINIB VERSUS MIDOSTAURIN OR BEST AVAILABLE THERAPY IN A REAL-WORLD SETTING (EBMT 2025) - P=N/A, P2 | "In IPTW-weighted Cox analysis, DOT was significantly longer in avapritinib versus midostaurin patients (HR [95% CI]: 0.37 [0.19, 0.70]; p=0.002).2L+ analysis: The avapritinib cohort included 67 patients, and the BAT cohort included 73 patients, contributing data on 104 lines of therapy (LOTs). Agent-level information was available for 89 LOTs in the BAT cohort, and common 2L+ agents were midostaurin (46.1%), cladribine (32.6%), and hydroxyurea (7.9%)... This study supports the use of avapritinib as 1L treatment for AdvSM, demonstrating significant OS and DOT benefits compared with 1L midostaurin. These results affirm that AdvSM patients with prior treatment experienced significantly improved OS and DOT on avapritinib compared to patients treated with BAT in the real world. Clinical Trial Registry: N/A"

Clinical • Metastases • Real-world • Real-world evidence • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

Cognitive toxicity of avapritinib: A case series (Sarcoma-RC 2025) - "Legal entity responsible for the study Axel de Bernardi. Funding Has not received any funding."

Clinical • Alzheimer's Disease • Cerebral Hemorrhage • Cognitive Disorders • Oncology • PDGFRA • PDGFRB