In a phase II trial reported in the Journal of Clinical Oncology, Martinelli et al found that blinatumomab (Blincyto) produced complete responses in patients with relapsed/refractory Philadelphia chromosome–positive (Ph+) B-precursor acute lymphoblastic leukemia (ALL) progressing after failure of tyrosine kinase inhibitor–based therapy.
The study included 45 patients from 19 European and U.S. centers who had relapsed after or were refractory to at least one second-generation or later tyrosine kinase inhibitor or were intolerant to second-generation or later tyrosine kinase inhibitors and intolerant or refractory to imatinib. Blinatumomab was given via continuous infusion at 9 mg/day in week 1 of cycle 1 followed by 28 mg/d thereafter; each treatment cycle consisted of 4 weeks of continuous infusion followed by 2 weeks off. The primary endpoint was complete remission or complete remission with partial hematologic recovery (CRh) during the first two cycles.
Responses and Toxicity
Complete remission/CRh during the first 2 cycles was achieved in 16 patients (36%, 95% confidence interval = 22%–51%), including 4 of 10 patients with T315I mutation. Complete minimal residual disease response was observed in 14 of complete remission/CRh responders (88%). Subsequent allogeneic hematopoietic stem cell transplantation was performed in 7 responders (44%), including 6 of 11 (55%) who had no prior transplantation. Median relapse-free survival and overall survival were 6.7 months and 7.1 months.
The most common adverse events were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Grade 1 or 2 cytokine-release syndrome occurred in 3 patients (7%), and 3 patients (7%) had grade 3 neurologic events, including a case of aphasia, which required temporary treatment interruption.
The investigators concluded: “Single-agent blinatumomab showed antileukemia activity in high-risk patients with Ph+ ALL who had relapsed or were refractory to [tyrosine kinase inhibitors]. [Adverse events] were consistent with previous experience in Ph+ ALL.”
The study was supported by Amgen.
Giovanni Martinelli, MD, of S. Orsola University Hospital, Bologna, is the corresponding author of the Journal of Clinical Oncology article.
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