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FDA approves Besponsa for acute lymphoblastic leukemia
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The FDA today approved inotuzumab ozogamicin for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.
Inotuzumab ozogamicin (Besponsa; Wyeth Pharmaceuticals, Pfizer) is an investigational antibody-drug conjugate comprised of a monoclonal antibody that targets CD22 — an antigen expressed on cancer cells in most patients with B-cell ALL — linked to a cytotoxic agent.
“The approval of Besponsa is an important step forward for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia, a rare disease that can be fatal within a matter of months if left untreated,” Liz Barrett, global president of Pfizer Oncology, said in a company-issued press release.
The approval included data from the randomized, open-label, international, multicenter INO-VATE ALL study, designed to compare inotuzumab ozogamicin with standard-of-care chemotherapy in 326 patients with relapsed or refractory B-cell precursor ALL.
Researchers randomly assigned patients to receive inotuzumab ozogamicin (n = 164) or investigator’s choice of chemotherapy (n = 162).
More patients assigned inotuzumab ozogamicin achieved complete remission (81% vs. 29%) and proceeded to transplantation (48% vs. 22%) than patients assigned chemotherapy. Further, of the patients who achieved complete remission, minimal residual disease negativity also occurred in more patients assigned inotuzumab ozogamicin (78% vs. 28%).
“Bespona will help address a significant need for new treatment options in B-cell acute lymphoblastic leukemia, and may help more patients reach stem cell transplant, which provides the best chance for long-term remission,” Barrett said. “We’re proud to build on our continued commitment to patients with hematologic malignancies, and will continue our work to find new treatments in acute lymphoblastic leukemia and other blood cancers.”
Median OS was 7.7 months (95% CI, 6.0-9.2) among patients treated with inotuzumab ozogamicin compared with 6.2 months (95% CI, 4.7, 8.3) among patients treated with chemotherapy. However, this difference did not meet the prespecified boundary for statistical significance (HR = 0.75; 97.5% CI, 0.57-0.99).
The most common adverse reactions associated with inotuzumab ozogamicin included thrombocytopenia, neutropenia, infection, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, gamma-glutamyl transferase increased and hyperbilirubinemia.
Infection, thrombocytopenia, hyperbilirubinemia, transaminases increased and hemorrhage were the most common adverse events leading to permanent discontinuation of treatment.
The U.S. labeling for inotuzumab ozogamicin includes a boxed warning for hepatotoxicity, including hepatic veno-occlusive disease — which occurred in 14% of patients — and increased risk for post-transplant nonrelapse mortality. Post-transplant nonrelapse mortality occurred in more patients treated with inotuzumab ozogamicin than chemotherapy (39% vs. 22%).
The FDA recommended a dose of 1.8 mg/m² inotuzumab ozogamicin administered as three divided doses on days 1, 8 and 15 for the first cycle. The recommended dosing for subsequent cycles is dependent on response to treatment.