Frederick L Locke1, David B Miklos1, Caron A Jacobson1, Miguel-Angel Perales1, Marie-José Kersten1, Olalekan O Oluwole1, Armin Ghobadi1, Aaron P Rapoport1, Joseph McGuirk1, John M Pagel1, Javier Muñoz1, Umar Farooq1, Tom van Meerten1, Patrick M Reagan1, Anna Sureda1, Ian W Flinn1, Peter Vandenberghe1, Kevin W Song1, Michael Dickinson1, Monique C Minnema1, Peter A Riedell1, Lori A Leslie1, Sridhar Chaganti1, Yin Yang1, Simone Filosto1, Jina Shah1, Marco Schupp1, Christina To1, Paul Cheng1, Leo I Gordon1, Jason R Westin1. 1. From the H. Lee Moffitt Cancer Center, Tampa, FL (F.L.L.); Stanford University School of Medicine, Stanford (D.B.M.), and Kite, a Gilead company, Santa Monica (Y.Y., S.F., J.S., M.S., C.T., P.C.) - both in California; Dana-Farber Cancer Institute, Boston (C.A.J.); Memorial Sloan Kettering Cancer Center, New York (M.-A.P.), and the University of Rochester School of Medicine, Rochester (P.M.R.) - both in New York; Amsterdam Medical Center, University of Amsterdam, Cancer Center Amsterdam, Amsterdam (M.-J.K.), University Medical Center Groningen, Groningen (T.M.), and University Medical Center Utrecht, Utrecht (M.C.M.) - all in the Netherlands; Vanderbilt-Ingram Cancer Center (O.O.O.) and Sarah Cannon Research Institute and Tennessee Oncology (I.W.F.) - both in Nashville; Washington University School of Medicine, St. Louis (A.G.); the Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore (A.P.R.); the University of Kansas Cancer Center, Kansas City (J. McGuirk); the Swedish Cancer Institute, Seattle (J.M.P.); Banner M.D. Anderson Cancer Center, Gilbert, AZ (J. Muñoz); the University of Iowa, Iowa City (U.F.); Bellvitge Institute for Biomedical Research, Universitat de Barcelona, Hematology Department, Institut Català d'Oncologia-Hospitalet, Barcelona (A.S.); University Hospitals Leuven, Leuven, Belgium (P.V.); the Division of Hematology, University of British Columbia and Leukemia-Bone Marrow Transplant Program of British Columbia, Vancouver General Hospital, BC Cancer, Vancouver, Canada (K.W.S.); Peter MacCallum Cancer Centre, Royal Melbourne Hospital and the University of Melbourne, Melbourne, VIC, Australia (M.D.); the University of Chicago Medical Center (P.A.R.) and Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University (L.I.G.) - both in Chicago; John Theurer Cancer Center, Hackensack, NJ (L.A.L.); the Centre for Clinical Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom (S.C.); and the University of Texas M.D. Anderson Cancer Center, Houston (J.R.W.).
Abstract
BACKGROUND: The prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor. METHODS: In this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was event-free survival according to blinded central review. Key secondary end points were response and overall survival. Safety was also assessed. RESULTS: A total of 180 patients were randomly assigned to receive axi-cel and 179 to receive standard care. The primary end-point analysis of event-free survival showed that axi-cel therapy was superior to standard care. At a median follow-up of 24.9 months, the median event-free survival was 8.3 months in the axi-cel group and 2.0 months in the standard-care group, and the 24-month event-free survival was 41% and 16%, respectively (hazard ratio for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; P<0.001). A response occurred in 83% of the patients in the axi-cel group and in 50% of those in the standard-care group (with a complete response in 65% and 32%, respectively). In an interim analysis, the estimated overall survival at 2 years was 61% in the axi-cel group and 52% in the standard-care group. Adverse events of grade 3 or higher occurred in 91% of the patients who received axi-cel and in 83% of those who received standard care. Among patients who received axi-cel, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21%. No deaths related to cytokine release syndrome or neurologic events occurred. CONCLUSIONS: Axi-cel therapy led to significant improvements, as compared with standard care, in event-free survival and response, with the expected level of high-grade toxic effects. (Funded by Kite; ZUMA-7 ClinicalTrials.gov number, NCT03391466.).
BACKGROUND: The prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor. METHODS: In this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was event-free survival according to blinded central review. Key secondary end points were response and overall survival. Safety was also assessed. RESULTS: A total of 180 patients were randomly assigned to receive axi-cel and 179 to receive standard care. The primary end-point analysis of event-free survival showed that axi-cel therapy was superior to standard care. At a median follow-up of 24.9 months, the median event-free survival was 8.3 months in the axi-cel group and 2.0 months in the standard-care group, and the 24-month event-free survival was 41% and 16%, respectively (hazard ratio for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; P<0.001). A response occurred in 83% of the patients in the axi-cel group and in 50% of those in the standard-care group (with a complete response in 65% and 32%, respectively). In an interim analysis, the estimated overall survival at 2 years was 61% in the axi-cel group and 52% in the standard-care group. Adverse events of grade 3 or higher occurred in 91% of the patients who received axi-cel and in 83% of those who received standard care. Among patients who received axi-cel, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21%. No deaths related to cytokine release syndrome or neurologic events occurred. CONCLUSIONS: Axi-cel therapy led to significant improvements, as compared with standard care, in event-free survival and response, with the expected level of high-grade toxic effects. (Funded by Kite; ZUMA-7 ClinicalTrials.gov number, NCT03391466.).
Authors: Miguel-Angel Perales; Larry D Anderson; Tania Jain; Saad S Kenderian; Olalekan O Oluwole; Gunjan L Shah; Jakub Svoboda; Mehdi Hamadani Journal: Transplant Cell Ther Date: 2022-06-26
Authors: Zinaida Good; Jay Y Spiegel; Bita Sahaf; Meena B Malipatlolla; Zach J Ehlinger; Sreevidya Kurra; Moksha H Desai; Warren D Reynolds; Anita Wong Lin; Panayiotis Vandris; Fang Wu; Snehit Prabhu; Mark P Hamilton; John S Tamaresis; Paul J Hanson; Shabnum Patel; Steven A Feldman; Matthew J Frank; John H Baird; Lori Muffly; Gursharan K Claire; Juliana Craig; Katherine A Kong; Dhananjay Wagh; John Coller; Sean C Bendall; Robert J Tibshirani; Sylvia K Plevritis; David B Miklos; Crystal L Mackall Journal: Nat Med Date: 2022-09-12 Impact factor: 87.241
Authors: Pashna N Munshi; Yue Chen; Kwang W Ahn; Farrukh T Awan; Amanda Cashen; Geoffrey Shouse; Mazyar Shadman; Paul Shaughnessy; Joanna Zurko; Frederick L Locke; Aaron M Goodman; Jose C Villaboas Bisneto; Craig Sauter; Mohamad A Kharfan-Dabaja; Gabrielle Meyers; Samantha Jaglowski; Alex Herrera; Mehdi Hamadani Journal: Transplant Cell Ther Date: 2022-05-21