Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium

• Published in: Journal of clinical oncology Vol. 38; no. 27; pp. 3119 - 3128
• Main Authors: Nastoupil, Loretta J, Jain, Michael D, Feng, Lei, Spiegel, Jay Y, Ghobadi, Armin, Lin, Yi, Dahiya, Saurabh, Lunning, Matthew, Lekakis, Lazaros, Reagan, Patrick, Oluwole, Olalekan, McGuirk, Joseph, Deol, Abhinav, Sehgal, Alison R, Goy, Andre, Hill, Brian T, Vu, Khoan, Andreadis, Charalambos, Munoz, Javier, Westin, Jason, Chavez, Julio C, Cashen, Amanda, Bennani, N Nora, Rapoport, Aaron P, Vose, Julie M, Miklos, David B, Neelapu, Sattva S, Locke, Frederick L
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 20.09.2020
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, CD19 - adverse effects; Antigens, CD19 - therapeutic use; Biological Products; Clinical Trials, Phase II as Topic; Comorbidity; Cytokine Release Syndrome - etiology; Female; Humans; Immunotherapy, Adoptive - adverse effects; L-Lactate Dehydrogenase - blood; Leukapheresis; Lymphoma, Large B-Cell, Diffuse - therapy; Male; Middle Aged; Organizational Policy; Original Reports; Patient Selection; Progression-Free Survival; Recurrence; Retrospective Studies; Severity of Illness Index; Standard of Care - standards; Survival Rate; Young Adult
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.19.02104

Axicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of the single-arm phase II ZUMA-1 trial, which showed best overall and complete response rates in infused patients of 83% and 58%, respectively. We report clinical outcomes with axi-cel in the standard-of-care (SOC) setting for the approved indication. Data were collected retrospectively from all patients with relapsed/refractory LBCL who underwent leukapheresis as of September 30, 2018, at 17 US institutions with the intent to receive SOC axi-cel. Toxicities were graded and managed according to each institution's guidelines. Responses were assessed as per Lugano 2014 classification. Of 298 patients who underwent leukapheresis, 275 (92%) received axi-cel therapy. Compared with the registrational ZUMA-1 trial, 129 patients (43%) in this SOC study would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis. Among the axi-cel-treated patients, grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 7% and 31%, respectively. Nonrelapse mortality was 4.4%. Best overall and complete response rates in infused patients were 82% (95% CI, 77% to 86%) and 64% (95% CI, 58% to 69%), respectively. At a median follow-up of 12.9 months from the time of CAR T-cell infusion, median progression-free survival was 8.3 months (95% CI, 6.0 to15.1 months), and median overall survival was not reached. Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 and elevated lactate dehydrogenase had shorter progression-free and overall survival on univariable and multivariable analysis. The safety and efficacy of axi-cel in the SOC setting in patients with relapsed/refractory LBCL was comparable to the registrational ZUMA-1 trial.