The addition of blinatumomab to standard frontline treatment of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) alternating with high-dose methotrexate and cytarabine resulted in promising survival rates at 3 years among patients with B-cell acute lymphoblastic leukemia (ALL), according to the results of a phase 2 study published in the journal Lancet Haematology.
Previous studies showed that high rates of minimal residual disease (MRD) can be achieved with blinatumomab among patients with relapsed/refractory B-ALL. The objective of this study was to determine if the use of blinatumomab in the front line can improve outcomes.
The single-arm, phase 2 study treated 38 patients with previously untreated B-ALL with 4 cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine and followed by 4 cycles of blinatumomab consolidation. Patients also received maintenance therapy with 15 cycles of alternating 6-mercaptopurine, vincristine, methotrexate, and prednisone (POMP) and blinatumomab. The primary endpoint was relapse-free survival (RFS).
At baseline, the median age of the cohort was 37 and 32% of patients were female. There were 55% of patients who were White, 32% who were Hispanic, 5% who were non-Hispanic Black, and 3% who were Asian. There were 27% of patients with a TP53 mutation and 8% had complex karyotype.
At 3 years, the RFS was 73% with a median follow-up of 37 months. The 3-year RFS was higher among patients without high-risk features at 82%, whereas patients with at least 1 high-risk feature had an RFS of 66%.
MRD negativity was achieved by 97% of patients during the trial, with 86% reaching negativity before their first dose of blinatumomab. All of the 13% of patients who were MRD-positive before blinatumomab achieved negativity after 1 cycle.
The OS was 81% at 3 years for the entire cohort, and was 88% for patients who achieved MRD-negativity after 1 cycle of chemotherapy and 75% among patients who did not.
Infections were the most coming grade 3-4 nonhematologic adverse events (AEs), and occurred in 37% and 71% of patients during induction and consolidation, respectively. Grade 3 cytokine release syndrome occurred in 1 patient and 4 patients developed grade 3 blinatumomab-related neurotoxicity.
The authors concluded that “front-line sequential chemotherapy with blinatumomab resulted in encouraging long-term survival.” They advocated for future randomized studies of the addition of blinatumomab to the treatment of B-ALL.
Disclosures: This study was supported by Amgen. Please see the original reference for a full list of disclosures.
Jabbour E, Short NJ, Jain N, et al. Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: a single-arm, single-centre, phase 2 trial. Lancet Haematol. Published online October 21, 2022. doi: 10.1016/S2352-3026(22)00285-X