Blinatumomab Nearly Doubles Overall Survival in B-Cell Precursor Acute Lymphoblastic Leukemia
Drug may offer an effective alternative to chemotherapy for patients with leukemia.
Blinatumomab (Blincyto) significantly improved overall survival in a phase 3 study of high-risk adult patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) compared with standard of care (SOC) chemotherapy.
The findings were from the randomized, open-label TOWER study, which examined the efficacy of blinatumomab versus SOC chemotherapy in 405 adult patients with Ph- relapsed or refractory B-cell precursory ALL, according to a press release.
Patients were randomized 2:1 to receive either blinatumomab (n=271) or treatment with investigator choice of 1 of 4 protocol-defined SOC chemotherapy regimens (n=134). The primary endpoint was overall survival (OS), and key secondary endpoints included complete remission within 12 weeks, the combined endpoint of complete remission plus complete remission with partial or incomplete hematologic recovery and event-free survival.
Additionally, secondary endpoints included remission duration, minimal residual disease (MRD) remission (<10—4), allogeneic stem cell transplant (alloSCT) rate, and adverse event (AE) rates, the press release stated.
The results of the analysis showed that the medical overall survival (OS) was 7.7 months for blinatumomab compared with 4 months of SOC.
“Historically, patients with relapsed or refractory ALL have a poor prognosis, with an overall survival of just 4 months on standard of care chemotherapy,” said Max S. Topp, MD, professor and head of Hematology, University Hospital of Wuerzburg, Germany. “Findings from this head-to-head study showed that [blinatumomab] almost doubled the median overall survival from 4 to 7.7 months, offering these high-risk patients a much-needed alternative to chemotherapy that is both innovative and effective.”
The survival benefit for blinatumomab was independent of alloSCT, as the median OS, censored at the time of alloSCT, was 6.9 months for blinatumomab compared with 3.9 months for SOC, according to the release.
Improvements observed in OS were generally consistent, regardless of age, prior alloSCT, or prior salvage therapy. However, the magnitude of benefit appeared to be greatest in earlier lives of salvage.
For AEs, neutropenia and infection that was greater than or equal to Grade 3 appeared to be less frequent in patients administered blinatumomab compared with SOC. Neurological events appeared at a similar rate between arms.
“Adults with Ph- relapsed or refractory B-cell precursor ALL are in critical need of new treatment options,” said Hagop M Kantarjian, MD, professor and chair of the Department of Leukemia, University of Texas MD Anderson Cancer Center. “Results from the TOWER study reinforce[s] the potential of the single agent bispecific T cell engager immunotherapy, which helped a higher percentage of patients achieve minimal residual disease response versus standard of care chemotherapy, highlighting the depth and quality of remissions achieved.”
Blinatumomab is the first and only bispecific CD 19-directed CD3 T cell engager immunotherapy to demonstrate OS benefit in patients with Ph- relapsed or refractory ALL.
Findings for the key secondary endpoints showed that remission rates were also higher for blinatumomab compared with SOC. In the blinatumomab arm, 34% of patients achieved complete remission versus 16% in the SOC arm. Additionally, patients in the blinatumomab arm had a higher rate of combined complete remission or complete remission with partial or complete hematologic recovery (44% versus 25%, respectively.)
Among the patients with complete remission or complete remission with partial or complete hematologic recovery, 76% achieved MRD negative status in the blinatumomab group compared with 48% in the SOC group. Additionally, of these patients, the median duration of remission was 7.3 months in the blinatumomab group versus 4.6 months in the SOC group.
For the key secondary efficacy endpoint of event-free survival, 6-month estimates in the blinatumomab and chemotherapy groups were 30.7% and 12.5%, respectively, and the HR was 0.55, favoring blinatumomab, according to the release.
“As the first study of an immunotherapy to demonstrate overall survival benefit in adult patients with Ph- relapsed or refractory B-cell precursor ALL, TOWER represents an important advance in the understanding of this aggressive, ultra-orphan disease,” Sean E. Harper, MD, executive vice president of Research and Development at Amgen. “As demonstrated by the data published today in the New England Journal of Medicine, [blinatumomab] has proven to improve overall survival, extend remission rates, and reduce minimal residual disease in these high-risk patients who previously have had limited effective options.