Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis

Author:

Reiter Andreas1,Schwaab Juliana1,DeAngelo Daniel J.2ORCID,Gotlib Jason3,Deininger Michael W.4ORCID,Pettit Kristen M.5,Alvarez-Twose Iván6,Vannucchi Alessandro M.7ORCID,Panse Jens8ORCID,Platzbecker Uwe9ORCID,Hermine Olivier10,Dybedal Ingunn11ORCID,Lin Hui-Min12,Rylova Svetlana N.13,Ehlert Katrin14,Dimitrijević Saša13,Radia Deepti H.15

Affiliation:

1. 1Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany

2. 2Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

3. 3Division of Hematology, Stanford Cancer Institute/Stanford University School of Medicine, Stanford, CA

4. 4Versiti Blood Research Institute and Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI

5. 5Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI

6. 6Institute of Mastocytosis Studies of Castilla-La Mancha (CLMast) and Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Spanish Reference Center of Mastocytosis, Toledo, Spain

7. 7Center for Research and Innovation of Myeloproliferative Neoplasms (CRIMM), Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy

8. 8Department of Oncology, Hematology, Hemostaseology, and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany

9. 9Clinic and Polyclinic for Hematology, Cell Therapy and Hemostaseology, Leipzig University, Leipzig, Germany

10. 10Department of Hematology, Rare Diseases Reference Center for Mastocytoses (CEREMAST), Assistance Publique-Hôpitaux de Paris (APHP)-Necker-Enfants Malades Hospital, and Imagine Institute-INSERM U1163, Paris University, Paris, France

11. 11Department of Hematology, Oslo University Hospital, Oslo, Norway

12. 12Blueprint Medicines Corporation, Cambridge, MA

13. 13Blueprint Medicines International (Switzerland), Zug, Switzerland

14. 14Blueprint Medicines (Germany) GmbH, Munich, Germany

15. 15Guy’s & St Thomas’s NHS Foundation Trust, London, United Kingdom

Abstract

Abstract Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm, driven by the KIT D816V mutation in >90% of patients. Avapritinib, a potent, highly selective D816V-mutant KIT inhibitor, is approved for treatment of adults with AdvSM by the US Food and Drug Administration, regardless of prior therapy, and the European Medicines Agency for patients with prior systemic therapy, based on EXPLORER (#NCT02561988; clinicaltrials.gov) and PATHFINDER (#NCT03580655; clinicaltrials.gov) clinical studies. We present latest pooled efficacy and safety analyses from patients who received ≥1 systemic therapy prior to avapritinib in EXPLORER/PATHFINDER. Overall response rate in response-evaluable patients (n = 31) was 71% (95% confidence interval: 52% to 86%; 22/31), including 19% (6/31) with complete remission (CR)/CR with partial recovery of peripheral blood counts (CRh). Median time to response was 2.3 months, median time to CR/CRh was 7.4 months, and median duration of response (DOR) was not reached. Reductions ≥50% in bone marrow mast cell infiltration (89%), KIT D816V variant allele fraction (66%), serum tryptase (89%), and reductions ≥35% in spleen size (70%) occurred in most patients. Median OS was not reached (median follow-up 17.7 months). Avapritinib was effective in all AdvSM subtypes, regardless of number/type of prior therapies or poor prognostic somatic mutations. Treatment-related adverse events (TRAEs) were observed in 94% of patients, most commonly grade 1/2; 57% had TRAEs of at least grade 3; 81% remained on treatment at 6 months. Avapritinib in adults with AdvSM who received prior systemic therapy was generally well tolerated, with high response rates regardless of prior systemic therapy.

Publisher

American Society of Hematology

Subject

Hematology

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