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FDA Approves Three New Treatments in Hematology and Oncology in October

In October, the US Food and Drug Administration (FDA) approved three new agents for hematology and oncology, including a second chimeric antigen receptor modified T-cell (CAR T-cell) therapy, a Bruton’s tyrosine kinase (BTK) inhibitor for mantle cell lymphoma, and an IV formulation of rolapitant.

  • New CAR T-Cell Therapy Approved for Non-Hodgkin Lymphoma. On 18 October, the FDA approved axicabtagene ciloleucel (axi-cel, [YESCARTA, Kite Pharma, Inc]), a CD19-targeting CAR T-cell therapy, for treatment of adults with relapsed or refractory non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and transformed follicular lymphoma. Patients must have received two or more lines of systemic therapy prior to receiving CAR T-cell therapy. Axi-cel single dose (2×106 CAR T cells/kg) is administered after a fludarabine and cyclophosphamide conditioning regimen. Approval was based on an overall response rate (ORR) of 82% and complete response (CR) rate of 54% observed in 101 patients treated on the phase II ZUMA-1 trial. The median duration of response was 8.2 months. Median overall survival was not reached, however 80% of patients were alive at 6 months. The most common grade ≥3 treatment-related adverse events (AEs) were neutropenia (66%), leukopenia (44%), anemia (43%), febrile neutropenia (31%), and encephalopathy (21%). Cytokine release syndrome (CRS) occurred in 13% of patients in the ZUMA-1 study and 3 patients died from CRS-related complications. Axi-cel will carry a boxed warning regarding the risk of CRS.
  • Acalabrutinib Approved for Relapsed Mantle Cell Lymphoma. On 31 October, the selective BTK inhibitor acalabrutinib (CALQUENCE®, AstraZeneca) received accelerated approval for treatment of patients with mantle cell lymphoma who have been treated with at least one prior therapy. The approval was based on results from the open-label, phase II ACE-LY-004 trial, in which acalabrutinib (100 mg twice daily) resulted in an ORR of 81% and CR rate of 40% in 124 patients with relapsed or refractory mantle cell lymphoma. The most common AEs (≥20%) of any grade were anemia, thrombocytopenia, headache, neutropenia, diarrhea, fatigue, myalgia, and bruising.
  • Intravenous Formulation of Rolapitant Now Approved. An intravenous (IV) formulation of rolapitant (Varubi®, Tesaro), was approved on 25 October for use in combination with other antiemetic agents for the prevention of delayed chemotherapy-induced nausea and vomiting. Rolapitant tablets were approved by the FDA in 2015 for this indication. Approval of the IV formulation was based on a bioequivalence study demonstrating comparability of IV and oral formulations.

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