FDA Approves Three Agents for Hematologic Malignancies in March

Blinatumomab Received Accelerated Approval for Minimal Residual Disease–Positive ALL. On 29 March the United States Food and Drug Administration (FDA) expanded the indication of the CD19/CD3 bispecific T-cell engager blinatumomab (Blincyto®, Amgen) to include adult and pediatric patients with B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission (CR) with minimal residual disease (MRD) ≥0.1%. This decision was based on results from the single-arm phase II BLAST trial, in which 78% of MRD-positive patients achieved MRD negativity after one cycle of blinatumomab determined by assay with a minimum sensitivity of 0.01%. The median relapse-free survival (RFS) was 23.6 months for patients achieving MRD negativity on blinatumomab, and 5.7 months for patients who remained MRD positive. The safety profile was consistent with that seen with blinatumomab in relapsed/refractory ALL.

Nilotinib Now Available for Pediatric Patients With CML. The indication of the tyrosine kinase inhibitor (TKI) nilotinib (Tasigna®, Novartis) was expanded to include use in pediatric patients aged 1 year or older for treatment of Philadelphia chromosome (Ph)-positive chronic-phase chronic myeloid leukemia (CML) that is either newly diagnosed or resistant/intolerant to a previous TKI. This approval was based on results in 69 pediatric patients across two single-arm clinical trials. At 12 cycles, nilotinib treatment yielded major molecular response (MMR) in 60.0% of newly diagnosed patients and 40.9% of resistant/intolerant patients. In general, the safety profile was similar to the profile of nilotinib in adult patients with CML, with the exception that there were lower rates of hyperbilirubinemia and transaminase elevation in pediatric patients.

Brentuximab Vedotin With Chemotherapy for Newly Diagnosed Hodgkin Lymphoma. The CD30-targeting antibody-drug conjugate (ADC) brentuximab vedotin (Adcetris®, Seattle Genetics) was approved for use in combination with chemotherapy in newly diagnosed patients with stage III or IV classical Hodgkin lymphoma. The approval is based on the phase III ECHELON-1 trial (N = 1334), which compared brentuximab vedotin (BV) plus chemotherapy (doxorubicin, vinblastine, and dacarbazine [AVD]) to chemotherapy alone (AVD plus bleomycin [ABVD]) in newly diagnosed patients with stage III/IV Hodgkin lymphoma. BV plus AVD resulted in a 23% reduction in the risk of progression or death compared to ABVD, with a 2-year modified progression-free survival (PFS) rate of 82.1% versus 77.25% (HR 0.77, P = .035). Neutropenia was the most common adverse event associated with BV plus AVD, occurring in 58% of patients, 19% of whom had febrile neutropenia. Prophylactic granulocyte colony stimulating factor (GCSF) is recommended for patients treated with first-line BV plus AVD. Peripheral neuropathy occurred in 67% of patients treated with BV plus AVD compared to 43% who received ABVD, though it was reversible in 67% of patients.

primelines-approved