Copenhagen – The monoclonal antibody blinatumomab nearly doubled overall survival compared with standard chemotherapy among patients with relapsed or refractory B-cell precursor leukemia negative for the Philadelphia chromosome, investigators reported.
Among 405 patients enrolled in the TOWER study, a multicenter, open-label phase III trial, median overall survival for patients treated with blinatumomab (Blincyto) was 7.7 months, compared with 4.0 months for patients treated with one of four standard chemotherapy regimens (P = .012) reported Dr. Max S. Topp of Universitätsklinikum in Würzburg, Germany.
Dr. Max S. Topp
“Blinatumomab is the first immunotherapy agent to demonstrate an overall survival benefit when compared to chemotherapy in patients relapsing with adult acute lymphoblastic leukemia. It increases almost twofold the overall survival when compared to standard care. This was consistent in all subgroups that we were looking at, regardless of age, prior salvage therapy, or patients relapsing after an allo-transplantation,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.
The trial was halted early, after a preplanned interim analysis showed a clear survival benefit with blinatumomab.
Blinatumomab is a bispecific T-cell engager (BiTE) antibody designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. As previously reported, it has induced high complete remission rates in patients with relapsed or refractory acute lymphoblastic leukemia (ALL).
In May 2015, the Food and Drug Administration granted blinatumomab accelerated approval for the treatment of adult patients with relapsed/refractory Philadelphia chromosome–negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
In the TOWER trial, patients with relapsed/refractory BCP-ALL were randomly assigned on a 2:1 basis to receive either blinatumomab (271 patients) or standard chemotherapy (134), consisting of the investigator’s choice of one of four defined regimens (based on either anthracyclines, histone deacetylase inhibitors, high-dose methotrexate, or clofarabine).
The patients were further stratified by age, prior salvage therapy, and prior allogeneic stem cell transplant (alloSCT).
Patients assigned to receive blinatumomab received it in 6-week cycles consisting of continuous infusions of 9 mcg/day in week 1 of cycle 1, then 28 mcg/day for weeks 3-4, followed by 2 weeks off. Patients were pretreated with dexamethasone for prophylaxis against the cytokine release syndrome.
Patients whose disease was in remission following two induction cycles could be continued on therapy until relapse.
As noted, the trial was halted early, after 248 patients had died; the primary analysis had been planned to occur after 330 patients had died.
In addition to the superior survival rates, blinatumomab was associated with a higher rate of complete responses (39% vs. 19%, P less than .001) and combined complete responses, complete hematologic responses, and complete responses with incomplete recovery of counts (46% vs. 28%, P = .001).
In all, 19% of patients assigned to blinatumomab and 17% assigned to chemotherapy died on study. Grade 3 or greater adverse events included neutropenia (38% of patients and 58%, respectively), infections (34% and 52%), neurologic events (9% and 8%), and the cytokine release syndrome (5% vs. 0%).
Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who moderated the briefing, asked Dr. Topp whether there were plans to use blinatumomab earlier in the course of disease.
Dr. Topp agreed that it might be a valuable addition to upfront therapy, noting that blinatumomab has been shown in a small percentage of patients who are positive for minimal residual disease to convert to being negative for minimal residual disease, and that this conversion was associated with improved overall survival.