By Shreeya Nanda
Compared with standard chemotherapy, treatment with inotuzumab ozogamicin increases the rate of complete remission and allows a higher proportion of patients with relapsed or refractory acute lymphoblastic leukaemia (ALL) to subsequently receive stem-cell transplantation, research suggests.
"Because stem-cell transplantation is considered to be the only curative treatment option, the capacity of inotuzumab ozogamicin treatment to increase the number of patients who can proceed to transplantation after salvage therapy is encouraging", says the team led by Hagop Kantarjian (University of Texas MD Anderson Cancer Center, Houston, USA).
The phase III INO-VATE trial accrued a total of 326 patients with relapsed or refractory ALL who were scheduled to receive their first or second salvage therapy. Participants were randomly assigned to receive either intravenous inotuzumab ozogamicin 1.8 mg/m2 per cycle for up to six cycles or physician's choice of chemotherapy (either the combination of fludarabine, cytarabine and granulocyte colony-stimulating factor, cytarabine plus mitoxantrone, or high-dose cytarabine).
Of the first 218 enrolled patients who made up the intention-to-treat population for the primary analysis of complete remission, 80.7% of the 109 given inotuzumab ozogamicin achieved complete remission compared with 29.4% of the 109 treated with standard chemotherapy, a significant difference.
And significantly more patients were able to receive a stem-cell transplant after inotuzumab ozogamicin than after standard chemotherapy, at 41% versus 11%.
Inotuzumab ozogamicin - an anti-CD22 antibody conjugated to the cytotoxic antibiotic calicheamicin - also improved survival outcomes. In the total study population, progression-free survival was significantly longer in the inotuzumab ozogamicin (n=164) than in the control (n=162) arm, at a median of 5.0 and 1.8 months, respectively.
Median overall survival was also longer among inotuzumab ozogamicin-treated participants, at 7.7 months compared with 6.7 months for those given standard chemotherapy, but the difference did not meet the prespecified criteria for significance.
Thrombocytopenia and febrile neutropenia of at least grade 3 occurred less often in the inotuzumab ozogamicin than in the control group, at 37% versus 59% and 24% versus 49%, respectively.
But veno-occlusive liver disease within 2 years of randomisation was more common among patients who received inotuzumab ozogamicin, at 11% versus 1%, the study authors report in The New England Journal of Medicine.
They believe that the conditioning protocol may contribute to the risk of veno-occlusive disease, given that use of a dual- versus a single-alkylator conditioning regimen significantly predicted the development of veno-occlusive disease in multivariate analysis.
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N Engl J Med 2016; Advance online publication