FDA Approves Inotuzumab Ozogamicin (Besponsa) for ALL

The US Food and Drug Administration (FDA) today approved inotuzumab ozogamicin (Besponsa, Wyeth/Pfizer) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

“For adult patients with B-cell ALL whose cancer has not responded to initial treatment or has returned after treatment, life expectancy is typically low,” said Richard Pazdur, MD, of the FDA’s Center for Drug Evaluation and Research. “These patients have few treatments available, and today’s approval provides a new, targeted treatment option.”

The approval was based on results from INO-VATE ALL, an open-label, randomized trial in 326 patients with Philadelphia chromosome–negative or Philadelphia chromosome–positive relapsed or refractory B-cell precursor ALL.

Patients were randomly assigned to receive inotuzumab ozogamicin (n = 164) or investigator’s choice of chemotherapy (n = 162).

Trial participants were required to have ≥5% bone marrow blasts and to have received one or two previous induction chemotherapy regimens for ALL. Patients with Philadelphia chromosome–positive B-cell precursor ALL were required to have disease that failed treatment with at least one tyrosine kinase inhibitor and standard chemotherapy.

Of the initial 218 patients in the trial, 35.8% of the patients in the inotuzumab ozogamicin arm experienced complete remission (CR) for a median 8.0 months, and 89.7% of those patients achieved minimal residual disease (MRD)–negativity. Of the patients in the chemotherapy arm, 17.4% experienced CR for a median 4.9 months, and 31.6% of those had MRD-negativity.

Final results from INO-VATE ALL were first presented at the European Hematology Association (EHA) 2016 Congress and were simultaneously published online in the New England Journal of Medicine, as reported by Medscape Medical News.

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At the EHA 2016 Congress, Hagop P. Kantarjian, MD, who was the lead author of the INO-VATE ALL trial, said that the drug will be used in combinations in the future.

“In my opinion, inotuzumab is well tolerated with appropriate prevention measures, and my hope is that soon in the future, inotuzumab will be used not as a single agent but in combination with chemotherapy or with other antibodies,” said Dr Kantarjian, who is from University of Texas MD Anderson Cancer Center, Houston.

At the EHA 2016 Congress, another expert not involved in the study admired the new drug. “Clearly inotuzumab is a very effective drug,” said Shai Izraeli, MD, professor and head of functional genomics and the Childhood Leukemia Research Center at the Sheba Medical Center, Israel, at that time.

Dr Izraeli emphasized that any improvement in the treatment of this disease is important because the 5-year survival rate for patients with relapsed or refractory B-cell ALL is less than 10%.

According to the FDA, the most common adverse reactions (occurring in more than 20% of patients) were thrombocytopenia, neutropenia, infection, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, increases in transaminase level, abdominal pain, increases in gamma-glutamyltransferase level, and hyperbilirubinemia.

The most common adverse reactions (occurring in 2% or more of patients) that were reported as the reason for permanent discontinuation of treatment were infection, thrombocytopenia, hyperbilirubinemia, increases in transaminase level, and hemorrhage.

For the first cycle, the recommended dose of inotuzumab ozogamicin for all patients is 1.8 mg/m2 per cycle, administered as three divided doses on day 1 (0.8 mg/m2), day 8 (0.5 mg/m2), and day 15 (0.5 mg/m2). The recommended dosing for subsequent cycles depends on response to treatment.

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The FDA previously granted orphan drug and breakthrough therapy designations to inotuzumab ozogamicin for the treatment of ALL, as well as priority review.

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