FDA Approves New Acute Lymphoblastic Leukemia Treatment

The drug includes a boxed warning due to the risk of severe hepatotoxicity

The US Food and Drug Administration (FDA) has approved inotuzumab ozogamicin (Besponsa) for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in the adult population.

The trial that led to the approval, INO-VATE ALL, was a phase III trial that included 326 adult patients with relapsed or refractory B-cell ALL. Patients were randomized 1:1 to receive treatment with investigator’s choice of chemotherapy or inotuzumab ozogamicin.

The rate of complete remission was higher in patients treated with inotuzumab ozogamicin compared with chemotherapy (81% vs 29%), as was the rate of minimal residual disease (MRD) negativity (78% vs 28% with chemotherapy) among those who achieved complete remission. Hematopoietic stem cell transplantation was also more common in patients treated with inotuzumab ozogamicin (48% vs 22%).

Median overall survival was higher in the inotuzumab ozogamicin arm (7.7 months vs 6.2 months) but these results did not reach statistical significance.

“Based on the results seen in the INO-VATE ALL trial, Besponsa improved multiple efficacy measures, including rates of hematologic remission, MRD negativity, and stem cell transplantation,” said lead study investigator Hagop M. Kantarjian, MD, of the University of Texas MD Anderson Cancer Center, in a press release. “I look forward to seeing the impact this important new therapy may have on my patients.”

Common adverse events (AEs) associated with inotuzumab ozogamicin include abdominal pain, anemia, fatigue, febrile neutropenia, headache, hemorrhage, hyperbilirubinemia, infection, leukopenia, liver damage, nausea, neutropenia, pyrexia, and thrombocytopenia. Other serious AEs include infusion-related reactions, myelosuppression, and QT interval prolongation.

Inotuzumab ozogamicin includes a boxed warning due to the risk of severe hepatotoxicity, including sinusoidal obstruction syndrome or veno-occlusive disease (VOD). Treatment should be paused or reduced if hepatotoxicity occurs and ceased if VOD occurs. The boxed warning also includes an increased risk of death following hematopoietic stem cell transplantation.

Inotuzumab ozogamicin may cause harm to a fetus or newborn; as such, women who are pregnant or breastfeeding should not take the drug.

The FDA also recently approved blinatumomab (Blincyto) for the treatment of B-cell precursor ALL in adult and pediatric patients.