Blinatumomab Achieves 78% Complete MRD Response in Adults with MRD-Positive ALL
In this single-arm study, 116 adults with B-cell precursor ALL in haematologic remission but with persistent MRD (>=10^-3) received blinatumomab by continuous infusion. Complete MRD response was achieved in 78% of evaluable patients, and MRD responders had significantly longer relapse-free survival (23.6 vs 5.7 months) and overall survival (38.9 vs 12.5 months). The trial validated MRD by RT-PCR and flow cytometry as both a patient selection criterion and a predictive biomarker for treatment response.
The original study
Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia.
- Authors
- Gökbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, et al.
- Journal
- Blood
- Type
- Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
- PMID
- 29358182
Original abstract
Approximately 30% to 50% of adults with acute lymphoblastic leukemia (ALL) in hematologic complete remission after multiagent therapy exhibit minimal residual disease (MRD) by reverse transcriptase-polymerase chain reaction or flow cytometry. MRD is the strongest predictor of relapse in ALL. In this open-label, single-arm study, adults with B-cell precursor ALL in hematologic complete remission with MRD (≥10-3) received blinatumomab 15 µg/m2 per day by continuous IV infusion for up to 4 cycles. Patients could undergo allogeneic hematopoietic stem-cell transplantation any time after cycle 1. The primary end point was complete MRD response status after 1 cycle of blinatumomab. One hundred sixteen patients received blinatumomab. Eighty-eight (78%) of 113 evaluable patients achieved a complete MRD response. In the subgroup of 110 patients with Ph-negative ALL in hematologic remission, the Kaplan-Meier estimate of relapse-free survival (RFS) at 18 months was 54%. Median overall survival (OS) was 36.5 months. In landmark analyses, complete MRD responders had longer RFS (23.6 vs 5.7 months; P = .002) and OS (38.9 vs 12.5 months; P = .002) compared with MRD nonresponders. Adverse events were consistent with previous studies of blinatumomab. Twelve (10%) and 3 patients (3%) had grade 3 or 4 neurologic events, respectively. Four patients (3%) had cytokine release syndrome grade 1, n = 2; grade 3, n = 2), all during cycle 1. After treatment with blinatumomab in a population of patients with MRD-positive B-cell precursor ALL, a majority achieved a complete MRD response, which was associated with significantly longer RFS and OS compared with MRD nonresponders. This study is registered at www.clinicaltrials.gov as #NCT01207388.