Overall Survival Benefit in Relapsed and Refractory B-Cell ALL Patients Receiving Inotuzumab Ozogamicin
CD22 is expressed in more than 90% of cases of B-cell acute lymphoblastic leukemia (ALL). This evaluation assessed overall survival (OS) and progression-free survival (PFS) in adults with relapsed/refractory (r/r) ALL receiving InO versus standard care (SC).1
This global randomized phase 3 trial enrolled patients with r/r ALL, including approximately 15% of patients in each arm with Philadelphia-positive ALL, who were candidates for salvage therapy. Patients were randomized to InO on days 8 and 15 of a 21- to 28-day cycle for up to 6 cycles or SC (either fludarabine + cytarabine + granulocyte colony-stimulating factor [FLAG], Ara-C plus mitoxantrone, or high-dose Ara-C). The study has 2 primary end points: (1) OS and (2) complete remission (CR)/CR with incomplete hematologic recovery (CRi). Safety was assessed in all patients who received ≥1 doses of study drug. Per protocol, the final OS analysis was to be performed after observing approximately 248 events. As of March 2016, 252 events (122 with InO and 130 with SC) occurred.
The intent-to-treat analysis population included 326 patients. Both arms were well balanced for baseline stratification factors. OS was significantly improved in the InO arm. Median OS for InO was 7.7 months (95% confidence interval [CI], 6.0-9.2) versus 6.7 months for SC (95% CI, 4.9-8.3) with a hazard ratio (HR) of 0.77 (97.5% CI, 0.58-1.03; P
= 0.0203). The 2-year OS rate for InO was 23% (95% CI, 16%-30%) versus 10% for SC (95% CI, 5%-16%). The goal of demonstrating a statistically significant improvement in final OS with InO versus SC was not met at the prespecified significance level of 0.0104. It was noted, however, that the OS data departed from the proportional hazards assumption. Consequently, a restricted mean survival time analysis was applied and showed mean OS of 13.9 months for InO and 9.9 months for SC, a difference that met statistical significance (P
PFS was significantly longer with InO versus SC (HR, 0.45; 97.5% CI, 0.34-0.61; P
<0.0001). Median PFS was 5.0 months for InO (95% CI, 3.7-5.6) versus 1.8 months for SC (95% CI, 1.5-2.2).
Follow-up of previously reported end points, including objective response, minimal residual disease–negativity, and stem-cell transplant rates, were all superior in the InO arm compared with SC by protocol-specified criteria.
Updated safety results demonstrate a tolerability and toxicity profile consistent with prior reports. Veno-occlusive disease (VOD) and liver toxicity were more common in patients receiving InO compared with SC (13% vs 1% for VOD and 15% vs 8% for grade 3/4 GGT/AST elevation, respectively).
Researchers concluded that, compared with SC, InO results in longer OS and significantly prolonged PFS in adult patients with r/r ALL.
- Kantarjian H, et al. EHA 2016. Abstract LB2233.