Low leukemia burden improves blinatumomab efficacy in patients with relapsed/refractory B‐cell acute lymphoblastic leukemia

Abstract

Background A lower baseline bone marrow blast percentage (bBMB%) is associated with better outcomes in patients with B‐cell acute lymphoblastic leukemia (B‐ALL) receiving blinatumomab. The objective of this analysis was to investigate the association between bBMB% and treatment outcomes in relapsed/refractory (R/R) B‐ALL. Methods Data from five trials of blinatumomab for R/R B‐ALL were pooled for analyses. Patients were placed in one of three groups: group 1, ≥50% bBMBs; group 2, ≥25% to <50% bBMBs; group 3, ≥5% to <25% bBMBs. Response and survival outcomes were compared between groups. Results Data from 683 patients (166 pediatric, 517 adult) were analyzed. Collectively, patients in groups 2 and 3 had significantly higher odds of achieving a complete remission (CR) (odds ratio [OR], 3.50 [95% confidence interval (CI), 2.23–5.48] and 3.93 [95% CI, 2.50–6.18], respectively; p < .001) and minimal/measurable residual disease response (OR, 2.61 and 3.37, respectively; p < .001) when compared with group 1 (reference). Groups 2 and 3 had a 37% and 46% reduction in the risk of death (hazard ratio [HR], 0.63 and 0.54, respectively; p < .001) and a 41% and 43% reduction in the risk of an event (relapse or death) (HR, 0.59 and 0.57, respectively; p < .001) compared with group 1. No significant differences in response or survival outcomes were observed between groups 2 and 3. Seven of nine patients whose bBMB% was lowered to <50% with dexamethasone achieved CR with blinatumomab. Conclusion Any bBMB% <50% was associated with improved efficacy following blinatumomab treatment for R/R B‐ALL.

Lower leukemia burden maximizes the impact of blinatumomab therapy

“…This pooled study analysis from Queudeville et al 5 . reinforces the original suggestion from the TOWER study of reduced likelihood of response and higher risk of death in those treated with blinatumomab with >50% marrow blast burden.…”

“…This pooled study analysis from Queudeville et al 5 reinforces the original suggestion from the TOWER study of reduced likelihood of response and higher risk of death in those treated with blinatumomab with >50% marrow blast burden. Reassuringly, it also is consistent with real-world experience using blinatumomab in R/R Ph-negative B-ALL reported by Badar el al.…”

“…Reassuringly, it also is consistent with real‐world experience using blinatumomab in R/R Ph‐negative B‐ALL reported by Badar el al 6 . In a retrospective study of 276 patients treated with blinatumomab at multiple centers, the response rate (CR/CRi) was 65% and blinatumomab was found to be used outside of clinical trials for R/R B‐ALL in patients with median marrow blast burden of 40% (i.e., lower than the median leukemia burden in the studies evaluated by Queudeville et al 5 …”

“…If blinatumomab should become incorporated into front‐line treatment on the basis of emerging data, the currently reported study by Queudeville et al 5 . remains valuable as a systematic evaluation of what setting is associated with best responses to blinatumomab in patients with R/R Ph‐negative B‐ALL.…”

“…3 Given that MRD and relapsed disease lie on a spectrum of leukemia burden, the aforementioned early studies with blinatumomab made evident that this immunotherapy has more impact and higher response rates at lower leukemia burdens. In the present issue, Queudeville et al 5 pooled data from five trials in which blinatumomab was employed as a single agent for R/R B-ALL. They categorized patients in three groups: group 1 with ≥50% marrow blasts, group 2 with ≥25% to <50% marrow blasts, and group 3 with ≥5% to <25% marrow blasts.…”