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

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.

FIG 1.

Patient flow diagram. Axi-cel, axicabtagene ciloleucel; CAR, chimeric antigen receptor; CR, complete response; CRS, cytokine release syndrome; OS, overall survival; PFS, progression-free survival.

FIG 2.

Duration of response, progression-free survival (PFS), and overall survival (OS) estimates. (A) PFS from leukapheresis. (B) OS from leukapheresis. (C) PFS from axi-cel infusion. (D) OS from axi-cel infusion. (E) Duration of response in axicabtagene ciloleucel (axicel) responders.

FIG 3.

Progression-free survival (PFS) and overall survival (OS) estimates from axicabtagene ciloleucel (axi-cel) infusion, stratified by Eastern Cooperative Oncology Group performance status (ECOG PS) or baseline lactate dehydrogenase (LDH). (A) PFS by ECOG PS at baseline. (B) OS by ECOG PS at baseline. (C) PFS by LDH at conditioning. (D) OS by LDH at conditioning. E, events in a group; N, number of patients in a group.

FIG A1.

Contribution of patients by center. Banner, MD Anderson Cancer Center; CCF, Cleveland Clinic; KCI, Karmanos Cancer Institute; KUMC, University of Kansas Medical Center; Mayo, Mayo Clinic; MDACC, MD Anderson Cancer Center; Moffitt, H. Lee Moffitt Cancer Center & Research Institute; Stanford, Stanford University Medical Center; UCSF, University of California, San Francisco; UM, University of Miami; UMGCCC, University of Maryland Greenebaum Comprehensive Cancer Center; UNMC, University of Nebraska Medical Center; UPMC, University of Pittsburgh Medical Center; URMC, University of Rochester Medical Center; VUMC, Vanderbilt University Medical Center; WU, Washington University.

FIG A2.

(A) Progression-free survival (PFS) and (B) overall survival (OS) in patients who received axicabtagene ciloleucel infusions, stratified by the presence (yes) or absence (no) of any comorbidity at the time of leukapheresis that was a ZUMA-1 exclusion criterion. E, events in a group; N, number of patients in a group.