FDA Grants Regular Approval to Blinatumomab and Expands Indication to Include Philadelphia Chromosome-Positive B Cell ALL

Blinatumomab received accelerated approval in December 2014 for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL. This current supplement provides the confirmation of clinical benefit required under the accelerated approval and also expands the indication to include Philadelphia chromosome-positive relapsed or refractory B-cell precursor ALL.

The trial that confirmed clinical benefit was a randomized, open‑label, multicenter clinical trial (TOWER, NCT02013167) comparing blinatumomab to standard-of-care (SOC) chemotherapy in 405 patients with relapsed or refractory B-cell precursor ALL. Blinatumomab was administered at 9 mcg per day on days 1–7 and 28 mcg per day on days 8–28 for cycle 1 in a 42-day cycle, at 28 mcg per day on days 1–28 for cycles 2–5 in 42‑day cycles, and at 28 mcg per day on days 1–28 for cycles 6–9 in 84‑day cycles. The trial demonstrated a statistically significant improvement in overall survival (OS) for patients treated with blinatumomab compared to those treated with SOC (hazard ratio = 0.71; 95% CI = 0.55, 0.93, p = 0.012). The estimated median OS was 7.7 months in the blinatumomab arm (95% CI = 5.6, 9.6) and 4.0 months in the SOC arm (95% CI = 2.9, 5.3). An independent data monitoring committee recommended that the study end early for efficacy based on these results, which were prespecified in an interim analysis.

The inclusion of Philadelphia chromosome-positive relapsed or refractory B-cell precursor ALL in the indication was based on a single-arm, multicenter study (ALCANTARA, NCT02000427) enrolling 45 patients with Philadelphia chromosome-positive ALL. Patients either had disease resistant to second-generation tyrosine kinase inhibitors or were intolerant to second-generation tyrosine kinase inhibitors and had disease resistant to imatinib. In this population, 36% of the patients achieved a complete remission with complete or partial hematologic recovery. The median duration of remission was 6.7 months.

No new major adverse reactions of blinatumomab were identified in the above clinical trials. Dosage and administration schedule of blinatumomab is based on weight for patients weighing less than 45 kg and fixed dose for those 45 kg or greater. Patients should be premedicated with dexamethasone. Hospitalization is recommended at the beginning of the first and second cycles. Details are available in the full prescribing information (https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125557s008lbl.pdf).

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