Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma

Author(s): Frederick L. Locke, M.D., David B. Miklos, M.D., Ph.D., Caron A. Jacobson, M.D., Miguel-Angel Perales, M.D., Marie-José Kersten, M.D., Ph.D., Olalekan O. Oluwole, M.B., B.S., M.D., Armin Ghobadi, M.D., Aaron P. Rapoport, M.D., Joseph McGuirk, D.O., John M. Pagel, M.D., Ph.D., Javier Muñoz, M.D., Umar Farooq, M.D., et al., for All ZUMA-7 Investigators and Contributing Kite Members
Source: February 17, 2022 N Engl J Med 2022; 386:640-654 DOI: 10.1056/NEJMoa2116133
Lucio Gordan MD

Dr. Gordan's Thoughts

Significant enhancement in 2-year EFS with axi-cell versus rescue chemoimmunotherapy + ASCT in refractory-relapsed DLBC-NHL. Toxicities, costs, operational aspects of CAR T-cell remain significant barriers in community oncology. Hopefully, enhanced products, technologies will allow broader utilization of CAR T-cell in the future.

BACKGROUND

The prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor.

METHODS

Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma
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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. opens in new tab.)

Author Affiliations

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.).

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