Tag: hematology

  • FDA Approves Pivekimab Sunirine for BPDCN

    On May 27, 2026, the U.S. Food and Drug Administration (FDA) approved pivekimab sunirine-pvzy (Decnupaz), a CD123-directed antibody-drug conjugate delivering a DNA alkylating payload, for the treatment of adults with blastic plasmacytoid dendritic cell neoplasm (BPDCN).¹

    The approval was based on the phase 1/2 CADENZA study (NCT03386513), a multicenter, open-label, single-arm trial of 84 adults with BPDCN without evidence of active central nervous system disease. The study included 33 patients with treatment-naïve BPDCN and 51 patients with relapsed or refractory disease. The primary efficacy endpoint was complete remission or clinical complete remission (CR/CRc). Among patients with treatment-naïve BPDCN, 23 of 33 patients achieved CR/CRc (69.7%; 95% CI, 51.3%-84.4%), with a median duration of CR/CRc of 9.7 months. Among patients with relapsed or refractory BPDCN, 8 of 51 patients achieved CR/CRc (15.7%; 95% CI, 7.0%-28.6%), with a median duration of CR/CRc of 9.2 months.¹,²

    In CADENZA, the most common adverse events included peripheral edema (54%), fatigue (26%), and infusion-related reactions (26%). Grade 3 or higher adverse events included neutropenia (16%), thrombocytopenia (14%), and peripheral edema (12%).² The prescribing information includes a Boxed Warning for hepatotoxicity, including hepatic veno-occlusive disease, and warnings and precautions for infusion-related reactions, edema, sulfite allergic reactions, and embryo-fetal toxicity.¹

    References

    1. US Food and Drug Administration. FDA approves pivekimab sunirine-pvzy for blastic plasmacytoid dendritic cell neoplasm, an ultra-rare hematologic malignancy. Published May 27, 2026. Accessed May 28, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pivekimab-sunirine-pvzy-blastic-plasmacytoid-dendritic-cell-neoplasm-ultra-rare
    2. Pemmaraju N, Marconi G, Montesinos P, et al. Pivekimab sunirine in blastic plasmacytoid dendritic cell neoplasm. J Clin Oncol. 2026;44(10):861-873. doi:10.1200/JCO-25-02083.

  • Oral Menin-Based Triplet Shows Strong Early Activity in ND AML

    The phase II SAVE trial presented at the 2025 American Society of Hematology (ASH) Annual Meeting (Abstract 47) delivered early but compelling results from an all-oral regimen pairing the menin inhibitor revumenib with decitabine/cedazuridine and venetoclax for newly diagnosed acute myeloid leukemia (AML) with mutations in nucleophosmin 1 (NPM1) or rearrangements involving lysine methyltransferase 2A (KMT2A). Among an older, molecularly defined cohort, the combination produced rapid measurable residual disease (MRD)–negative remissions and encouraging early survival signals, raising the possibility that menin inhibition may meaningfully strengthen current low-intensity frontline approaches.

    The newly diagnosed cohort included 21 patients with a median age of 70 years. The NPM1-mutated cohort was older, with a median age of 73 years and 71% aged 70 years or older. Co-mutations were common and included NRAS, KRAS, fms-related tyrosine kinase 3 (FLT3), and isocitrate dehydrogenase 1/2 (IDH1/2). Myelodysplasia-related mutations were present in 43%. Treatment incorporated revumenib through Day 21 of induction to allow confirmation of Day 14 marrow findings before adjustment, and both venetoclax and decitabine/cedazuridine durations were reduced in later cycles as cytopenias emerged. The median cycle length extended to approximately six weeks because of delayed count recovery.

    The overall response rate (ORR) was 86%, and 81% of patients achieved complete remission (CR) or CR with partial hematologic recovery (CRh). All composite remissions were MRD negative by multiparameter flow cytometry with a sensitivity of 10^-4 NPM1-based MRD measured by next-generation sequencing (NGS; sensitivity 5 × 10^-5) showed similar kinetics, and the 2 patients who failed to clear ultimately relapsed. With nine months of median follow-up, the median duration of response (DOR), overall survival (OS), and event-free survival (EFS) had not been reached. Estimated one-year remission rates were 71% in NPM1-mutated AML and 80% in KMT2A-rearranged AML. Most responses occurred within the first cycle, and 33% of patients proceeded to allogeneic hematopoietic stem cell transplantation (HSCT) in first remission, and none of those patients have relapsed.

    Differentiation syndrome (DS) occurred in 19% of patients, including 2 grade 3 events that resolved with corticosteroids. QT interval prolongation occurred in 43% of patients but was limited to grade 2 and did not prompt treatment discontinuation. Infections reflected substantial myelosuppression, with gram-negative rod bacteremia representing the dominant pathogen group. Four deaths occurred including one patient who died post HCT of respiratory failure while receiving revumenib maintenance.

    Taken together, the SAVE trial offers early evidence that integrating a menin inhibitor into an oral hypomethylating agent–venetoclax backbone may produce deep and rapid remissions in newly diagnosed AML with NPM1 mutations or KMT2A rearrangements. Longer follow-up and larger cohorts will be required to define durability, safety in older adults, and the prevalence of resistance mechanisms such as MEN1 mutation.

    References:

    Jen WY, Short NJ, Farhat A, et al. Phase II study of the all-oral combination of revumenib with decitabine/cedazuridine and venetoclax (SAVE) in newly diagnosed AML. Presented at: American Society of Hematology Annual Meeting; 2025; Orlando, FL. Abstract 47.