Inotuzumab ozogamicin linked to better outcomes than standard chemotherapy for ALL: The INO-VATE ALL trial

1. Inotuzumab ozogamaxin (IO) demonstrated significantly higher complete remission rates and median progression-free survival compared to standard chemotherapy in relapsed acute lymphoblastic leukemia (ALL).

2. Among patients with complete remission, absence of minimal residual disease and progression to stem-cell transplantation was more common with IO.

Evidence Rating Level: 1 (Excellent) 

Study Rundown: Though chemotherapy often induces complete response in ALL, many patients relapse and become difficult to treat. Patients must be in complete remission to be eligible for stem cell transplantation which is considered the only cure for this aggressive form of leukemia. This study evaluated the safety and efficacy of the conjugated anti-CD22 antibody IO in the treatment of relapsed or refractory CD22-positive ALL. Primary endpoints included complete remission and overall survival. A significant increase in complete remission compared to standard therapy was demonstrated, but overall survival did not meet statistical significance. Moderate adverse events for IO were reported, including cytopenia, liver toxicity, and veno-occlusive disease (VOD). If approved, IO could bridge the gap to stem cell transplantation and increase the cure rate of ALL.

Click to read the study, published today in NEJM

Relevant Reading: Treatment of acute lymphoblastic leukemia

In-Depth [randomized controlled trial]: This study was an open label, phase III, randomized controlled trial that collected survival data on 326 patients with relapsed or refractory ALL from 18 countries. Participants were randomized to IO or standard chemotherapy. Of the 326 patients, the first 218 were included in the primary analysis (n = 109 in each group). The study used independent primary endpoints that included: complete remission with or without complete hematologic recovery and overall survival. Secondary endpoints included safety and other measures of efficacy, including duration of remission, progression-free survival, rate of subsequent transplantation, and patients in complete remission with minimal residual disease.

Treatment with IO was associated with a significantly higher rate of remission than standard chemotherapy (80.7%, 95%CI 72.1 to 87.7; vs. 29.4%, 95%CI 21.0 to 38.8, p < 0.001). There was no significant difference in overall survival according to the threshold preset by the primary analysis (HR 0.77, p = 0.04), but post hoc analysis of restricted mean survival time demonstrated longer mean overall survival (p = 0.005). In patients with complete remission, IO was associated with significantly lower rates of minimal residual disease (78.4% vs. 28.1%, p < 0.001), greater median duration of remission (4.6 vs. 3.1 months; HR 0.55; p = 0.03), and subsequent stem-cell transplantation (41% vs.11%, p < 0.001). Grade ³3 hematologic adverse events were more common in the standard chemotherapy group (thrombocytopenia 24% vs. 49%; platelet transfusion 64% vs. 95%; febrile neutropenia 24% vs. 49%). Liver-related adverse events and VOD occurred more frequently in the IO group.

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