Obinutuzumab versus Rituximab in young patients with advanced DLBCL, a PET-guided and randomized phase 3 study by LYSA.
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Le Gouill S, Ghesquieres H, Obéric L, Morschhauser F, Tilly H, Ribrag V, Lamy T, Thieblemont C, Maisonneuve HG, Gressin R, Bouabdallah K, Haioun C, Damaj G, Fornecker LM, Bouabdallah R, Feugier P, Sibon D, Cartron G, Bonnet C, André M, Chartier L, Ruminy P, Kraeber-Bodere F, Bodet-Milin C, Berriolo-Riedinger A, Briere J, Jais JP, Molina T, Itti E, Casasnovas O
Rituximab plus polychemotherapy is standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED trial compares obinutuzumab to rituximab. GAINED (NCT01659099) is an open-label, randomized phase 3 trial. Transplant-eligible patients (18-60yrs) with untreated aged-adjusted international prognostic index (aaIPI) ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab. Patients were stratified by aaIPI (1; 2-3) and chemotherapy regimen (ACVBP; CHOP). Consolidation treatment was determined according to response assessed by centrally reviewed interim semi-quantitative PET. Responders after cycle 2 and 4 (PET2-/PET4-) received planned immuno-chemotherapy consolidation. Responders only after cycle 4 (PET2+/4-) received high-dose methotrexate plus transplantation. The primary objective was an 8% improvement (HR=0.73; 80% power; alpha risk 2.5%; one-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. Events included death, progression, PET 2 or 4 positivity, modification of planned treatment. From September 20, 2012, 670 patients were enrolled (obinutuzumab n=336; rituximab n=334). 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP and 324 (48.4%) received ACVBP. Median follow-up was 38.7 months. The 2-year EFS were similar in obinutuzumab and rituximab groups (59.8% vs 56.6%; p=0.123; HR=0.88). The 2-year PFS in the whole cohort was 83.1% (95%CI 80-85.8). PET2-/4- and PET2+/4- had similar 2-year PFS and OS (89.9% vs 83.9%) and 94.8% vs 92.8%). The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in untreated aaIPI≥1 DLBCL transplant-eligible patients.
Blood. 2020 Nov 19;: