Blinatumomab May Benefit Patients With Philadelphia Chromosome-Positive B-Cell ALL

Blinatumomab (Blincyto) may induce complete remission within 2 cycles of treatment in adults with relapsed or refractory Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia (ALL), according to a new phase II open-label, single-arm, multicenter trial. Patients with this rare and rapidly progressing cancer of the blood and bone marrow have had few treatment options and these results are welcomed news for those patients with refractory disease.

A July 16, 2015 news release from Amgen reported that blinatumomab monotherapy induced a complete remission or complete remission with partial hematological recovery within 2 cycles of treatment in a clinically meaningful number of patients.¹ In addition, no new safety concerns were identified. The data will be presented at an upcoming medical conference and is being submitted for publication.

"These top-line results are encouraging and support blinatumomab as a potential treatment option for patients with relapsed or refractory Philadelphia chromosome-positive B-cell precursor ALL," said Sean Harper, MD, who is the executive vice president of Research and Development for Amgen, Thousand Oaks, Calif. " We are hopeful that our comprehensive ALL development program for blinatumomab, the first clinical and regulatory validation of the BiTE® platform, will continue to demonstrate clinical effectiveness for patients with this serious disease."

Approximately one-fourth of adult ALL expresses the oncogenic protein BCR-ABL1 that results from the t(9;22) chromosome translocation known as the Philadelphia chromosome. This study (Trial Design NCT02000427) consisted of a screening period, an induction treatment period (2 cycles of blinatumomab), a consolidation treatment period (up to 3 additional cycles of blinatumomab for applicable patients), and a safety follow-up visit 30 days after treatment. Following the safety follow-up visit, patients were followed for response duration and survival every 3 months for 18 months or death, whichever occurred first.

Blinatumomab is the first bispecific CD19-directed CD3 T-cell engager (BiTE®) antibody construct product, and the first single-agent immunotherapy to be approved by the US Food and Drug Administration (FDA) for the treatment of patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL.  Prior to approval, this agent was granted breakthrough therapy and continued approval for this indication is contingent upon verification of clinical benefit in subsequent trials.

The most commonly reported adverse reactions (≥ 20%) in clinical trials with this treatment so far have been pyrexia (62%), headache (36%), peripheral edema (26%), febrile neutropenia (26%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%) and constipation (20%). However, there are also considerable serious adverse effects associated with this treatment, including neurological toxicities and CRS (cytokine release syndrome). Approximately 50% of patients receiving this treatment in clinical trials experienced neurological toxicities. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 15% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The median time to onset of any neurological toxicity was 7 days.

References:

• Amgen News Releases. (2015). Amgen Announces Positive BLINCYTO® (blinatumomab) Phase 2 Study Results In Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Cell Precursor Acute Lymphoblastic Leukemia.