Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma
CAR-T for second line is better than standard of care, the question is: how about compared to BITE therapy? Future is exciting for those patients.
Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma
Author(s): Sattva S. Neelapu1;Caron A. Jacobson2;Armin Ghobadi3;David B. Miklos4;Lazaros J. Lekakis5;Olalekan O. Oluwole6;Yi Lin7;Ira Braunschweig8;Brian T. Hill9;John M. Timmerman10;Abhinav Deol11;Patrick M. Reagan12;Patrick Stiff13;Ian W. Flinn14;Umar Farooq15;Andre H. Goy16;Peter A. McSweeney17;Javier Munoz18;Tanya Siddiqi19;Alex F. Herrera19;Julio C. Chavez20;Nancy L. Bartlett21;Adrian A. Bot22;Rhine R. Shen22;Jinghui Dong22;Kanwarjit Singh22;Harry Miao22;Jenny J. Kim22;Yan Zheng22;Frederick L. Locke20
Source: Blood (2023) 141 (19): 2307–2315.
Dr. Anjan Patel's Thoughts
5-year survival data from the Zuma trials shows that there is curative potential in r/r DLBCL with cure rates near 50%.
KEY POINTS
Axicabtagene ciloleucel induced long-term survival with no new safety signals in patients with refractory LBCL. Durable responses were associated with expansion of chimeric antigen receptor T cells early after intravenous infusion.
ABSTRACT
In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we assessed outcomes in ZUMA-1 after 5 years of follow-up. Eligible adults received lymphodepleting chemotherapy followed by axi-cel (2 × 106 cells per kg). Investigator-assessed response, survival, safety, and pharmacokinetics were assessed in patients who had received treatment. The objective response rate in these 101 patients was 83% (58% complete response rate); with a median follow-up of 63.1 months, responses were ongoing in 31% of patients at data cutoff. Median overall survival (OS) was 25.8 months, and the estimated 5-year OS rate was 42.6%. Disease-specific survival (excluding deaths unrelated to disease progression) estimated at 5 years was 51.0%. No new serious adverse events or deaths related to axi-cel were observed after additional follow-up. Peripheral blood B cells were detectable in all evaluable patients at 3 years with polyclonal B-cell recovery in 91% of patients. Ongoing responses at 60 months were associated with early CAR T-cell expansion. In conclusion, this 5-year follow-up analysis of ZUMA-1 demonstrates sustained overall and disease-specific survival, with no new safety signals in patients with refractory LBCL. Protracted B-cell aplasia was not required for durable responses. These findings support the curative potential of axi-cel in a subset of patients with aggressive B-cell lymphomas. This trial was registered at ClinicalTrials.gov, as #NCT02348216.
Author Affiliations
1Division of Cancer Medicine, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX;2Dana-Farber Cancer Institute, Boston, MA;3Division of Medical Oncology, Washington University School of Medicine, St Louis, MO;4Department of Medicine–Med/Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA;5Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL;6Vanderbilt-Ingram Cancer Center, Nashville, TN;7Department of Hematology, Mayo Clinic, Rochester, MN;8Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY;9Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH;10Division of Hematology and Oncology, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA;11Karmanos Cancer Center, Wayne State University, Detroit, MI;12Department of Medicine, University of Rochester School of Medicine, Rochester, NY;13Loyola University Chicago Stritch School of Medicine, Maywood, IL;14Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN;15University of Iowa, Iowa City, IA;16John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ;17Colorado Blood Cancer Institute, Denver, CO;18Department of Hematology, Mayo Clinic, Phoenix, AZ;19Division of Lymphoma, City of Hope National Medical Center, Duarte, CA;20Moffitt Cancer Center, Tampa, FL;21Washington University School of Medicine and Siteman Cancer Center, St Louis, MO;22Kite, a Gilead Company, Santa Monica, CARelated Articles
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