Abstract

Background: Blinatumomab is a CD3/CD19 bispecific T-cell engager approved for the treatment of relapsed/refractory (R/R) or minimal residual disease (MRD)-positive B-cell precursor acute lymphoblastic leukemia (B-ALL). Recent phase 3 studies in children and young adults with B-ALL in first relapse suggested that blinatumomab used as consolidation after chemotherapy salvage could be more beneficial than given as single agent in overt relapse. Whereas current strategies aim to demonstrate the benefit of blinatumomab in first line, the optimal use of blinatumomab in adult patients with first B-ALL relapse still deserves to be further explored Aims: To evaluate the efficacy of blinatumomab given as consolidation in adults with B-ALL in a real-world setting Methods: We retrospectively included 115 consecutive patients with B-ALL treated with blinatumomab from April 2012 until June 2021 at Saint-Louis Hospital, Paris, France (n=100), and at AOU Città della Salute e della Scienza, Turin, Italy (n=15). Patients included in clinical trials were excluded. Patients were divided in three subgroups: 68 patients treated in 1st complete remission (CR1), 31 patients treated in 2nd CR after chemotherapy-base salvage therapy (CR2), and 16 patients treated in overt relapse (R/R). Patients in CR1 received blinatumomab for MRD persistence (n=59/68, 87%) or due to inability to receive standard consolidation (n=9/68, 13%, off-label use). The number of blinatumomab cycles along with the use of chemotherapy and/or of allogeneic hematopoietic stem cell transplant (alloHSCT) after blinatumomab was up to physician choice. Results: The median age of patients was 37 years (range, 15-84). Among the 115 patients, 24% (n=28) were Philadelphia (Ph)-positive. Age, sex, baseline disease features and genetic risk categories did not differ between subgroups. After blinatumomab a complete MRD-response was achieved in 83% of CR1 and 86% of CR2 patients (p=.99). A complete remission was reached by 9/15 R/R patients (60%). In the 3 subgroups, the median number of blinatumomab cycles given was 2 (range, 1-6). Forty-six patients (42%) treated in CR (41% CR1, 45% CR2) and 4 R/R patients (25%) were bridged to allo-HSCT in continuous CR after blinatumomab. With a median follow up of 3.1 years, 3-year DFS was 68% in CR1 and 67% in CR2 patients (p=0.41); 3-year OS was 80% in CR1 and 71% in CR2 patients (p=0.32). In R/R patients, 3-year DFS and OS were 13% and 20% respectively. Considering patients who received blinatumomab in CR (CR1+CR2), univariate analysis showed that higher MRD levels both before and after blinatumomab were associated with shorter DFS, while only MRD response to blinatumomab was associated with OS. Both pre- and post-blinatumomab MRD levels retained significance in bivariate analysis for DFS Image:Summary/Conclusion: The present study underlines the efficacy of blinatumomab in consolidation after chemotherapy-based salvage, showing comparable outcomes between patients treated in CR2 and CR1. In CR2 patients, promising DFS and OS were observed as compared to historical cohorts of patients treated with chemotherapy alone or with blinatumomab in overt relapse. Our data suggest that blinatumomab should be preferably used in consolidation rather than as salvage therapy in patients with B-ALL in first relapse

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