S1619 BLINATUMOMAB FOR MINIMAL RESIDUAL DISEASE (MRD) IN ADULTS WITH BCELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA (BCPALL): MEDIAN OVERALL SURVIVAL (OS) NOT REACHED AT 5 YEARS FOR COMPLETE MRD RESPONDERS
Authors: N. Goekbuget, H. Dombret, G. Zugmaier, M. Bonifacio, C. Graux, C. Faul, M.S. Topp, M. Brüggemann, K. Taylor, R. Bargou
Journal: HemaSphere (2019)

Background: MRD is the strongest predictor of relapse in BCP-ALL. Blinatumomab is a bispecific immunotherapy that redirects T cells to kill CD19+ target cells. In a single-arm study (BLAST; NCT01207388) in adults with BCP-ALL and MRD, we previously reported that 78% (88/113) of patients achieved a complete MRD response after cycle 1 of blinatumomab. Patient incidences of grade 3 or 4 adverse events, including neurologic events (13%) or cytokine release syndrome (2%), were consistent with previous blinatumomab studies. Aims: This report describes the final analysis of OS for adults with BCP-ALL and MRD in the BLAST study, with a minimum patient follow-up of 5 years after blinatumomab treatment. Methods: The BLAST study enrolled adults with BCP-ALL in first (CR1) or subsequent (CR2+) hematologic complete remission after ≥3 intensive chemotherapy blocks, with MRD (≥10−3) at least 2 weeks after the last chemotherapy. All patients received blinatumomab 15 μg/m2per day for up to 4 cycles. Each cycle was 4 weeks of continuous infusion and 2 weeks off. Complete MRD response was defined as no target amplification, with a minimum sensitivity of 10−4. After MRD response assessment (end of cycle 1), patients could undergo allogeneic hematopoietic stem cell transplantation (HSCT) at any time. Kaplan-Meier estimates of OS were determined after long-term follow-up (5 years). A conditional landmark of 45 days (the end of cycle 1) was used for subgroup analyses by complete MRD response. Results: Of 116 patients with MRD who received blinatumomab, OS was evaluated for 110 patients with Philadelphia chromosome–negative (Ph−) BCP-ALL and < 5% blasts at enrollment, including 74 who received HSCT in continuous complete remission (CCR) after blinatumomab. With a median follow-up of 59.8 months, median OS was 36.5 months (95% CI: 22.0-not estimable [NE]). At 5 years, outcomes with vs without HSCT in CCR were as follows: alive without relapse, 40.5% vs 19.4%; relapse, 23.0% vs 72.2%; and death without relapse, 36.5% vs 8.3%. Analyses of OS by complete MRD response in cycle 1 (n = 107) excluded patients with no central MRD assay (n = 1) or inadequate MRD test sensitivity (n = 2). Median OS was not reached (95% CI: 29.5 months-NE) for complete MRD responders (n = 84) and 14.4 months (95% CI: 3.8–32.3) for MRD nonresponders (n = 23; log-rank p = 0.002; Figure 1). Estimated 5-year survival was 43% overall (95% CI: 34%>52%) and 50% for complete MRD responders (95% CI: 39%>60%). Among HSCT recipients in CCR, median OS from HSCT was not reached (95% CI: 25.7 months-NE) for complete MRD responders (n = 61) and 16.5 months (95% CI: 1.1-NE) for MRD nonresponders (n = 10; log-rank p = 0.065). Among patients with MRD in CR1, median OS was not reached (95% CI: 29.5 months-NE) for complete MRD responders (n = 60) and 10.6 months (95% CI: 2.7–39.7) for MRD nonresponders (n = 13; p = 0.008).Summary/Conclusion: In the final, 5-year follow-up analysis of a multinational study of adults with BCP-ALL in hematologic complete remission with MRD, median OS was 36.5 months after blinatumomab treatment. Median OS was not reached among patients with a complete MRD response in cycle 1 of blinatumomab treatment. These results provide further support for long-term OS benefits associated with blinatumomab treatment in adults with BCP-ALL and MRD.