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A CD22 antibody-drug conjugate produced complete remission in 81% of adults with relapsed ALL compared with 29% on chemotherapy, at the cost of liver toxicity in about one in ten.
INO-VATE randomised 326 adults with relapsed or refractory CD22-positive B-cell ALL to inotuzumab ozogamicin or standard intensive salvage chemotherapy. The two primary endpoints were complete remission (analysed in the first 218 patients) and overall survival. Complete remission was 80.7% versus 29.4%, with MRD-negativity among responders 78.4% versus 28.1%, and median PFS 5.0 versus 1.8 months. Median OS was 7.7 versus 6.7 months (hazard ratio 0.77), which did not meet the prespecified boundary, although two-year survival was 23% versus 10%. Hepatic veno-occlusive disease occurred in 11% of inotuzumab patients, especially after subsequent transplant with dual-alkylator conditioning.
INO-VATE made inotuzumab a standard salvage therapy for adult ALL and a common route to transplant, and, with the TOWER trial of blinatumomab, moved adult ALL from chemotherapy-only salvage to immunotherapy. Both drugs have since been pulled into front-line regimens. The liver toxicity signal shaped how transplant conditioning is chosen after inotuzumab.
Shares Elias Jabbour, Hagop M. Kantarjian, Inotuzumab ozogamicin, CD22.
Shares Inotuzumab ozogamicin, Pfizer (incl. Seagen), Acute lymphoblastic leukaemia, Antibody-drug conjugate (ADC).
Shares Inotuzumab ozogamicin, CD22, Acute lymphoblastic leukaemia.
Shares Blinatumomab, Overall survival (OS), Minimal / molecular residual disease (MRD), New England Journal of Medicine.
Shares Overall survival (OS), Pfizer (incl. Seagen), Toxicity and quality of life are undervalued, New England Journal of Medicine.
Shares CD22, Acute lymphoblastic leukaemia.
Shares CD22, Acute lymphoblastic leukaemia.
Shares MD Anderson Cancer Center, Overall survival (OS), Toxicity and quality of life are undervalued, New England Journal of Medicine.