Blinatumomab doubled survival vs standard of care in first salvage for relapsed/refractory ALL
Blinatumomab more than doubled the overall survival (OS) vs standard-of-care (SOC) chemotherapy in the first salvage regimen in patients with Philadelphia chromosome-negative relapsed/refractory precursor B-cell acute lymphoblastic leukaemia (R/R BCP-ALL), according to a subset analysis of the TOWER* trial presented at the European Hematology Association (EHA) Congress 2017 held in Madrid, Spain.
“Adults with BCP-ALL often relapse following standard induction/consolidation chemotherapy. Prognosis following second and successive chemotherapy salvage regimens is poor compared with first salvage or frontline therapy, with less favourable outcomes among patients with shorter complete response duration,” according to lead author Professor Hervé Dombret of Hôpital Saint-Louis in Paris, France.
The current study is a subset analysis by salvage therapy status of the multinational phase III TOWER trial which randomized 405 patients with R/R BCP-ALL on a 2:1 ratio to intravenous blinatumomab (9 µg/day in week 1 of cycle 1, followed by 28 µg/day in cycles of 4 weeks on, 2 weeks off; n=271) or investigator’s choice of any one out of four SOC regimens (n=134). [EHA 2017, abstract 478]
Among patients undergoing the first salvage therapy, median OS was significantly higher in the blinatumomab than the SOC arms (11.1 vs 5.5 months; p=0.016). Similar trend toward higher OS with blinatumomab vs SOC was also observed in the subgroup undergoing second or successive salvage regimens (5.1 vs 3.0 months; p=0.055).
“Improved OS compared with SOC in [the first salvage for] patients supports earlier use of blinatumomab,” suggested Dombret.
Additionally, the blinatumomab arm showed consistently higher rate of complete remission than the SOC arm, with or without full haematologic recovery (CR/CRh/CRi**), in both subgroups of patients undergoing the first salvage (51.0 percent vs 36.5 percent; p=0.07) or second and successive salvage regimens (39.5 percent vs 14.1 percent; p<0.001).
Adverse events (AEs) of grade ≥3 occurred in fewer patients treated with blinatumomab vs SOC as the first salvage (61 percent vs 83 percent) and the second or successive salvage therapies (68 percent and 75 percent). Similar observations were also reported for grade ≥4 AEs in both the first salvage setting (34 percent vs 51 percent) and second or successive salvage settings (36 percent vs 54 percent).
The rates of neurologic events of grade ≥3 were similar in both the blinatumomab and the SOC arms regardless of salvage status (9 percent vs 9 percent in the first salvage; 10 percent vs 9 percent in the second or successive salvage).
Grade ≥3 cytokine release syndrome was reported more frequently in the blinatumomab vs the SOC arms, at rates of 4 percent in the first salvage and 5 percent in the second or successive salvage settings vs none in the SOC group.