COPENHAGEN—Interim results from the phase 3 TOWER trial suggest blinatumomab can prolong overall survival (OS) when compared to standard care in adults with Ph-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia (B-ALL).
The median OS for patients treated with blinatumomab was nearly double the median OS of patients who received standard chemotherapy (investigator’s choice of 4 different regimens).
Based on these results, Amgen, the company sponsoring the trial, decided to stop it early.
“This was the first study to show that immunotherapy can outcompete chemotherapy,” said Max S. Topp, MD, of University Hospital of Wuerzburg in Germany.
Dr Topp presented results from this study at the 21st Congress of the European Hematology Association (abstract S149).
Patients and treatment
The TOWER trial enrolled and randomized 405 patients with Ph-negative, relapsed/refractory B-ALL, and 376 of them ultimately received treatment.
The patients received blinatumomab (n=267) or investigator’s choice of 1 of 4 protocol-defined standard chemotherapy regimens (n=109):
- FLAG (fludarabine, high-dose cytarabine, and granulocyte-colony stimulating factor), with or without an anthracycline (n=49, 45%)
- A high-dose cytarabine-based regimen (n=19, 17%)
- A high-dose methotrexate-based regimen (n=22, 20%)
- A clofarabine-based regimen (n=19, 17%).
Patients who received blinatumomab received it as a continuous infusion, 4 weeks on and 2 weeks off, at 9 µg/day for 7 days, then 28 µg/day on weeks 2-4. They received 2 cycles of induction, which was followed by 3 cycles of consolidation if they had ≤5% blasts.
If patients still had ≤5% blasts after consolidation, they received up to 12 months of blinatumomab maintenance. Maintenance was a continuous infusion, 4 weeks on and 8 weeks off, at 28 µg/day.
Patient characteristics were similar between the treatment arms. The median age was 37 in both arms (overall range, 18-80). About 40% of patients in the blinatumomab arm and 50% in the chemotherapy arm had not received any prior salvage regimens.
More than 30% of patients in both arms had undergone an allogeneic hematopoietic stem cell transplant (allo-HSCT), and about 20% were primary refractory. Roughly 30% of blinatumomab-treated patients were refractory to salvage therapy, as were more than 20% of chemotherapy-treated patients.
Response and survival
During induction, in the intent-to-treat population (n=271 in the blinatumomab arm and 134 in the chemotherapy arm), the overall response rate was 44% in the blinatumomab arm and 25% in the chemotherapy arm (P<0.001). The complete response rates were 34% and 16%, respectively.
Among patients who received their assigned treatment (n=267 in the blinatumomab arm and 109 in the chemotherapy arm), the overall response rates were 45% and 30%, respectively (P=0.007).
In the intent-to-treat population, the median OS was 7.7 months (95% CI, 5.6-9.6) in the blinatumomab arm and 4 months (95% CI, 2.9-5.3) in the chemotherapy arm (hazard ratio=0.71, P=0.012). The survival curves were similar in the as-treated population.
Dr Topp noted that the improvement in OS with blinatumomab was consistent across subgroups, regardless of age, prior salvage therapy, or prior allo-HSCT.
Dr Topp and his colleagues also considered the effect post-treatment allo-HSCT might have on OS. Sixty-five patients in the blinatumomab arm and 32 in the chemotherapy arm went on to receive an allo-HSCT (24% of patients in both arms).
When the researchers censored for post-treatment allo-HSCT, the median OS was 6.9 months in the blinatumomab arm and 3.9 months in the chemotherapy arm (hazard ratio=0.66, P=0.004).
Safety
In the as-treated population, 99% of patients in both arms experienced adverse events (AEs).
The incidence of grade 3 AEs was 37% in the blinatumomab arm and 30% in the chemotherapy arm. The incidence of grade 4 AEs was 31% and 44%, respectively. The incidence of grade 5 AEs was 19% and 17%, respectively.
Grade 3 or higher AEs of interest, according to Dr Topp, were infection (34% with blinatumomab and 52% with chemotherapy), neutropenia (38% and 58%, respectively), neurologic events (9% and 8%, respectively), and cytokine release syndrome (5% and 0%, respectively).
Seven patients—5 in the blinatumomab arm and 2 in the chemotherapy arm—who did not undergo allo-HSCT died during the study without documented relapse.
