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, CA

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