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

J Clin Oncol. 2020 Sep 20;38(27):3119-3128. doi: 10.1200/JCO.19.02104. Epub 2020 May 13.

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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
  • Patient Selection
  • Progression-Free Survival
  • Recurrence
  • Retrospective Studies
  • Severity of Illness Index
  • Standard of Care / standards
  • Survival Rate
  • Young Adult

Substances

  • Antigens, CD19
  • Biological Products
  • L-Lactate Dehydrogenase
  • axicabtagene ciloleucel