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.

• Authors: Loretta J Nastoupil, Michael D Jain, Lei Feng, Jay Y Spiegel, Armin Ghobadi, Yi Lin, Saurabh Dahiya, Matthew Lunning, Lazaros Lekakis, Patrick Reagan, Olalekan Oluwole, Joseph McGuirk, Abhinav Deol, Alison R Sehgal, Andre Goy, Brian T Hill, Khoan Vu, Charalambos Andreadis, Javier Munoz, Jason Westin, Julio C Chavez, Amanda Cashen, N Nora Bennani, Aaron P Rapoport, Julie M Vose, David B Miklos, Sattva S Neelapu, Frederick L Locke
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 38 Issue 27 Pg. 3119-3128 (09 20 2020) ISSN: 1527-7755 [Electronic] United States
• PMID: 32401634 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, CD19 (adverse effects, 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