Obinutuzumab vs rituximab for advanced DLBCL: a PET-guided and randomized phase 3 study by LYSA
Steven Le Gouill, Hervé Ghesquières, Lucie Oberic, Franck Morschhauser, Hervé Tilly, Vincent Ribrag, Thierry Lamy, Catherine Thieblemont, Hervé Maisonneuve, Rémy Gressin, Krimo Bouhabdallah, Corinne Haioun, Gandhi Damaj, Luc Fornecker, Réda Bouhabdallah, Pierre Feugier, David Sibon, Guillaume Cartron, Christophe Bonnet, Marc André, Loic Chartier, Philippe Ruminy, Françoise Kraeber-Bodéré, Caroline Bodet-Milin, Alina Berriolo-Riedinger, Josette Brière, Jean-Philippe Jais, Thierry Jo Molina, Emmanuel Itti, René-Olivier Casasnovas, Steven Le Gouill, Hervé Ghesquières, Lucie Oberic, Franck Morschhauser, Hervé Tilly, Vincent Ribrag, Thierry Lamy, Catherine Thieblemont, Hervé Maisonneuve, Rémy Gressin, Krimo Bouhabdallah, Corinne Haioun, Gandhi Damaj, Luc Fornecker, Réda Bouhabdallah, Pierre Feugier, David Sibon, Guillaume Cartron, Christophe Bonnet, Marc André, Loic Chartier, Philippe Ruminy, Françoise Kraeber-Bodéré, Caroline Bodet-Milin, Alina Berriolo-Riedinger, Josette Brière, Jean-Philippe Jais, Thierry Jo Molina, Emmanuel Itti, René-Olivier Casasnovas
Abstract
Rituximab plus polychemotherapy is the standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED, a randomized phase 3 trial, compared obinutuzumab to rituximab. Transplant-eligible patients (18-60 years) with an untreated age-adjusted International Prognostic Index (aaIPI) score ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab and stratified by aaIPI (1; 2-3) and chemotherapy regimen (doxorubicin, cyclophosphamide, prednisone plus vindesine, bleomycin [ACVBP] or vincristine [CHOP]). Consolidation treatment was determined according to response to interim positron emission tomography (PET). Responders after cycle 2 and 4 (PET2-/PET4-) received immunochemotherapy. Responders after only cycle 4 (PET2+/4-) received transplantation. The primary objective was an 8% improvement (hazard ratio [HR] = 0.73; 80% power; α risk, 2.5%; 1-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. From September 2012, 670 patients were enrolled (obinutuzumab, n = 336; rituximab, n = 334). A total of 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP. Median follow-up was 38.7 months. The 2-year EFS was similar in both groups (59.8% vs 56.6%; P = .123; HR = 0.88). The 2-year PFS in the whole cohort was 83.1% (95% confidence interval, 80% to 85.8%). PET2-/4- and PET2+/4- had similar 2-year progression-free survival (PFS) and overall survival (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 aaIPI ≥1 DLBCL transplant-eligible patients. This trial was registered at www.clinicaltrials.gov as #NCT01659099.
© 2021 by The American Society of Hematology.
Source: PubMed