The FDA sets a Prescription Drug User Fee Action date of June 21, 2024 for blinatumomab as a treatment for those with CD19-positive B-cell precursor acute lymphoblastic leukemia.
The FDA has granted priority review to a supplemental biologics license application (sBLA) for blinatumomab (Blincyto) as a treatment for patients with early-stage, CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL), according to a press release from Amgen.1
The regulatory agency set a Prescription Drug User Fee Action date of June 21, 2024 for their decision on approving blinatumomab in the aforementioned population. Supporting findings for the sBLA came from the phase 3 E1910 study (NCT02003222) assessing chemotherapy with or without blinatumomab in newly diagnosed adult patients with B-ALL.
According to results presented at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition, the rate of morphologic complete remission (CR/CRi) following induction chemotherapy was 81%.2 Additionally, after a median follow-up of 43 months, the median overall survival (OS) was not reached (NR) in the blinatumomab plus chemotherapy arm compared with 71.4 months in the chemotherapy arm (HR, 0.42; 95% CI, 0.24-0.75; P = .003).
“The addition of blinatumomab to consolidation chemotherapy resulted in a significantly better [OS] in [patients] with newly diagnosed B-lineage ALL who were measurable residual disease [MRD] negative after intensification chemotherapy,” the study authors wrote. “No significant safety concerns were noted. The addition of blinatumomab to consolidation chemotherapy in adult [patients] aged 30 to 70 years represents a new standard of care for BCR::ABL1-negative ALL.”
Patients enrolled on this trial were randomly assigned to receive blinatumomab with or without chemotherapy. Following induction chemotherapy, patients received 4 additional cycles of consolidation chemotherapy or 2 cycles of blinatumomab for 28 days of each cycle. After completing consolidation chemotherapy with or without blinatumomab, 6-mercaptopurine plus vincristine, methotrexate, and prednisone (POMP) maintenance therapy was administered for 2.5 years.
The trial’s primary end point was OS. Secondary end points included relapse-free survival (RFS), MRD status, and adverse effects.
Patients between the ages of 30 and 70 years with newly diagnosed B-ALL and Philadelphia chromosome (Ph–) negativity were able to enroll on the trial. Additional eligibility criteria included having no history of recent myocardial infarction, normal cardiac ejection fraction, and an ECOG performance status of 0 to 3.
Those with mature B-ALL or a concurrent active malignancy for which they were already receiving treatment were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had intercurrent organ damage, an antecedent hematologic disorder, or an active uncontrolled infection. Having clinically relevant central nervous system pathology including epilepsy, seizure, aphasia, stroke, dementia, Parkinson’s disease, cerebellar disease, or psychosis was also grounds for exclusion from enrollment.
Investigators are also evaluating blinatumomab in combination with low-intensity chemotherapy in older adult patients with Ph– B-ALL as part of the phase 3 Golden Gate study (NCT04994717). The trial is still open for enrollment, and developers plan to amend the study to allow for patients to receive blinatumomab subcutaneously, which is expected to take place in the second half of 2024.
The primary end points of the Golden Gate study include treatment-emergent adverse effects during the safety run-in portion and event-free survival and OS in the phase 3 portion. Secondary end points include health-related quality of life, RFS, and MRD status.
Additionally, subcutaneous administration of blinatumomab in adult patients with relapsed/refractory Ph– B-ALL is currently under evaluation in a phase 1/2 study; patient enrollment for this study is still underway.