Oncology News Burst from FDA: Blinatumomab

Wednesday, July 12, 2017

From the Society for Immunotherapy of Cancer

In cooperation with the Food and Drug Administration (FDA), and as a service to our members, SITC will periodically distribute information about newly approved therapies for cancer patients. This helps FDA inform oncologists and professionals in oncology-related fields of recent approvals in a timely manner. Included in the email from the FDA will be a link to the product label, which will provide the relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, SITC does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described. The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On July 11, 2017, the U.S. Food and Drug Administration approved blinatumomab (BLINCYTO®, Amgen Inc.) for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children.

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/day on days 1‑7 and 28 mcg/day on days 8‑28 for cycle 1 in a 42-day cycle, at 28 mcg/day on days 1‑28 for cycles 2‑5 in 42‑day cycles, and at 28 mcg/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 upon these results that 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 hematological 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 <45 kg and fixed dose for those ≥45 kg. 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.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).