A supplemental biologics license application was filed for Blincyto to be approved for certain patients with ALL.
The FDA received a supplemental biologics license application (sBLA) for the full regulatory approval of Blincyto (blinatumomab) for patients who have Philadelphia chromosome-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), according to the developer of the anti-CD19 immunotherapy, Amgen.
The sBLA was based on data from the phase 3 TOWER study, in which the median overall survival (OS) with Blincyto was 7.7 months versus four months with standard chemotherapy. The application also provides data supporting the use of Blincyto in patients with Philadelphia chromosome-positive (Ph+) relapsed/refractory B-cell precursor ALL.
"Acute lymphoblastic leukemia is one of the most aggressive B-cell malignancies, and adult patients who relapse or are refractory to treatment often go through multiple lines of therapy," Sean E. Harper, M.D., executive vice president of Research and Development at Amgen, said in a statement. "We are excited to potentially receive full approval for Blincyto, the first immunotherapy to demonstrate an overall survival benefit versus standard of care chemotherapy in patients with relapsed or refractory Ph- B-cell precursor ALL, and bring a much needed new treatment option to those who are Ph+."
The open-label phase 3 TOWER trial randomized 405 patients in a 2 to 1 ratio to Blincyto (271 patients) or investigator’s choice of one of four standard chemotherapy regimens (134 patients). The median patient age was 37 years in both arms. Other baseline characteristics were also well balanced in the Blincyto versus the standard chemotherapy arm, including median bone marrow blasts (80 percent vs 79 percent), prior salvage therapy (56 percent vs 52 percent) and prior allogeneic stem cell transplant (alloSCT; 35 percent vs 34 percent).
Blincyto was administered in six-week cycles of four weeks on (continuous infusion of 9 µg/d in week one of cycle one, then 28 µg/d) and two weeks off. Patients received dexamethasone prior to Blincyto to prevent cytokine release syndrome. If remission was reached following two induction cycles, patients were allowed to receive treatment until relapse. OS was the primary efficacy endpoint. Complete remission (CR) and combined CR or CR with partial or incomplete hematologic recovery (CR/CRh/CRi) were secondary outcome measures.
Treatment with Blincyto reduced the risk of death by 29 percent versus standard chemotherapy. The OS benefit with Blincyto was observed across prespecified patient subgroups based on age, prior salvage therapy, or alloSCT. The study was halted early for efficacy based on the recommendation of an independent data monitoring committee.
The CR rate with Blincyto was 39 percent versus 19 percent with standard chemotherapy. The combined CR/CRh/CRi rates were 46 percent versus 28 percent, respectively.
The safety analysis was based on 376 patients who received at least 1 dose of Blincyto (267 patients) or standard chemotherapy (109 patients). Of these patients, 57 percent and 25 percent, in the Blincyto and chemotherapy arms, respectively, started at least two cycles.
The adverse event (AE) profile was similar between the two arms and consistent with previous studies of Blincyto. The incidence of all-grade AEs was 99 percent in both treatment arms. Grade 3 AEs occurred in 37 percent of the Blincyto arm and 30 percent of the standard chemotherapy arm. The rates of grade 4 AEs were 31 percent and 44 percent, respectively. Grade 5/fatal AEs occurred in 19 percent of the Blincyto arm versus 17 percent of the chemotherapy arm, including grade 5 infection rates of 11 percent and 12 percent, respectively.
Grade 3 or higher AEs of interest included neutropenia (38 percent in the Blincyto arm vs 58 percent in the standard chemotherapy arm), infection (34 percent vs 52 percent), neurologic events (9 percent vs 8 percent) and cytokine release syndrome (5 percent vs 0).
The FDA granted an accelerated approval to Blincyto in 2014 as a treatment for patients with Ph- relapsed/refractory B-precursor ALL, based on findings from a phase 2 trial.
According to Amgen, the BLINCYTO label includes a Boxed Warning regarding cytokine release syndrome and neurological toxicities.