Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab (R-InO) versus chemotherapy for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (B-NHL).

Background: InO is an anti‐CD22 antibody conjugated to calicheamicin; R‐InO has shown activity in pts with relapsed/refractory aggressive B‐NHL in a phase 1/2 study (Fayad, J Clin Oncol 2013; 31, 573‐583: ORR, 74% and 20% for relapsed and refractory pts, respectively). Methods: This randomized, phase 3 trial (NCT01232556 ) compared efficacy and safety of R‐InO (R 375 mg/m2 IV‐day [d] 1; InO 1.8 mg/m2 IV‐d 2 [each cycle]; 28 d cycles) vs investigator's choice (IC: R‐bendamustine [R‐B: R 375 mg/m2 IV‐d 1, B 120 mg/m2‐d 1 and d 2 each cycle] or R‐gemcitabine [R‐G: R 375 mg/m2 IV‐d 1, 8, 15, 22 cycle 1, d 1 all other cycles; G 1000 mg/m2‐d 1, 8, 15 each cycle]) in adults with relapsed/refractory CD22+ aggressive B‐NHL; not candidates for high‐dose chemotherapy. Endpoints were OS (primary), PFS, ORR (CR + PR); safety. A planned interim analysis based on 108 events (~40% of planned OS events) was conducted in May, 2013 when enrollment was stopped for futility. We present preliminary results for all enrolled pts. Results: 338 pts were enrolled (age >65 y, 68%; DLBCL, 91%; sIPI [>4], 24%; best prior response of progressive disease [PD], 28%; previous time‐to‐progression >12 mo, 32%). See Table for efficacy results. Most common AEs (R‐InO vs IC): thrombocytopenia (59% vs 37%), neutropenia (32% vs 47%), nausea (29% vs 33%), fatigue (33% vs 25%), and leukopenia (21% vs 31%). 2 R‐InO pts had venoocclusive disease (VOD) on study treatment (1 additional pt had VOD after an allotransplant and ~13 mo after 1 R‐InO dose). Treatment‐related death occurred in 6 pts (4 R‐InO, 2 IC). Among R‐InO vs IC pts, 28% vs 15% discontinued due to AEs; 53% vs 57% due to PD. Conclusions: Although R‐InO activity was observed, there was no statistical difference in ORR, PFS, or OS between R‐InO vs IC treated pts. R‐InO was not superior to IC among subgroups analyzed to date (to be presented). Poorer outcomes in this phase 3 study vs the phase 1/2 study may reflect more refractory pts in this study.