According to a phase III study, the antibody–drug conjugate inotuzumab ozogamicin is more likely to induce complete remissions, with full or incomplete hematologic recovery, in patients with relapsed or refractory acute lymphocytic leukemia. Data from a phase I study of another antibody–drug conjugate, vadastuximab talirine, demonstrates that it is safe and effective against acute myeloid leukemia.
Two investigational antibody–drug conjugates (ADC) have shown positive results against acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML), according to study results presented during the 21st Congress of the European Hematology Association in Copenhagen, Denmark, in June.
Patients with relapsed or refractory ALL typically have to achieve a complete remission before receiving an allogeneic stem-cell transplant, the only potential cure. Intensive chemotherapy usually doesn't produce complete remissions, however, and phase II investigations have suggested that inotuzumab ozogamicin (Pfizer), which targets CD22 on B cells, might perform better. Hagop Kantarjian, MD, of The University of Texas MD Anderson Cancer Center in Houston, presented data—simultaneously published in The New England Journal of Medicine—from a randomized phase III study of this ADC (N Engl J Med 2016 June 12 [Epub ahead of print]).
Kantarjian and colleagues assigned 326 patients with relapsed or refractory ALL to receive either inotuzumab ozogamicin or a standard chemotherapy regimen. In an analysis of the first 218 patients, 80.7% of individuals in the ADC arm had a complete remission (CR) with full or incomplete hematologic recovery, the latter meaning their blood counts didn't return to normal. In contrast, 29.4% of patients who received chemotherapy achieved these milestones. As a result, 41% of patients who received inotuzumab ozogamicin were able to have a stem cell transplant, versus 11% of those who received chemotherapy.
For the entire group of 326 patients, the median progression-free survival was 5 months for the inotuzumab ozogamicin arm and 1.8 months for the standard chemotherapy arm.
Side effects of the ADC included blockage of small veins in the liver, a potentially fatal complication.
Because many patients with AML are older, they can't tolerate aggressive chemotherapy and instead receive hypomethylating agents, which are less likely to produce remissions. Amir Fathi, MD, of Harvard Medical School in Boston, MA, reported data from a phase I study of vadastuximab talirine (Seattle Genetics) in 53 patients who received the CD33-targeting ADC in combination with the hypomethylating agents azacitidine or decitabine as first-line therapy.
Among 49 evaluable patients, 41% had CRs and 30% had CRs with incomplete hematologic recovery. The median relapse-free survival was 7.7 months. Adverse events were mainly hematologic, with 45% of patients developing febrile neutropenia, for instance, and 53% developing thrombocytopenia. Overall, vadastuximab talirine plus a hypomethylating agent “is a highly promising combination that requires further study,” Fathi says.
For Mark Litzow, MD, of the Mayo Clinic in Rochester, MN, who wasn't involved with either study, “it's very exciting to see the complete remission rate is 80%” in the ALL trial. Vadastuximab talirine plus hypomethylating agents also has potential against AML, he says. “I think this is impressive early data.” –Mitch Leslie
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