Axi-cel treatment for B-cell lymphoma provides real-world outcomes comparable to ZUMA-1 trial data

April 19, 2019

The U.S. lymphoma CAR-T consortium, 17 academic centers including Mayo Clinic that are certified to provide Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR)-T cell therapy, reported clinical outcomes on the first 274 patients treated with axicabtagene ciloleucel (axi-cel) for relapsed or refractory diffuse large B-cell lymphoma in the real-world practice. Results indicate that 30-day responses in the real-world setting were comparable to the best responses observed on the pivotal ZUMA-1 clinical trial that led to the FDA approval of this therapy, and safety also appeared to be comparable ― despite nearly half of the study patients failing to meet ZUMA-1 eligibility criteria.

Study authors included Nabila (Nora) N. Bennani, M.D., and Yi Lin, M.D., Ph.D., with Hematology and the CAR-T Cell Therapy Program at Mayo Clinic in Rochester, Minnesota. Study outcomes were presented at the American Society of Hematology (ASH) Annual Meeting and published in Blood in 2018. ZUMA-1 trial results were published in the New England Journal of Medicine in 2017, with longer term two-year follow-up results published in The Lancet Oncology in 2019.

Axi-cel is an autologous anti-CD19 CAR-T cell therapy approved by the FDA in 2017 for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, transformed lymphoma, and high-grade B-cell lymphoma who have failed at least two prior lines of systemic therapy.

In the ZUMA-1 trial, 108 patients with relapsed or refractory diffuse large B-cell lymphoma were treated with axi-cel. Grade 3 or higher cytokine release syndrome by Lee criteria and neurological events occurred in 11 percent and 32 percent of the patients, respectively. The best overall response rate was 83 percent. The complete response rate was 58 percent. At a median follow-up of 24 months, 34 percent of the patients had ongoing remission and median overall survival has not been reached.

Real-world practice demonstrates similar safety and efficacy

Study outcomes presented at the ASH Annual Meeting reflect patient characteristics and treatment course data for the 274 patients infused with axi-cel (Yescarta) in the real-world practice, including:

  • Median age: 60 (range 21-83)
  • Sex: 65 percent male
  • Eastern Cooperative Oncology Group (ECOG) performance status: ECOG 0-1 (81 percent of patients), ECOG 2 (15 percent) and ECOG 3 (4 percent)
  • Histology: 68 percent of patients had diffuse large B-cell lymphoma including high-grade B-cell lymphoma; 26 percent had transformed lymphoma; 6 percent had primary mediastinal large B-cell lymphoma

Bridging therapy (primarily chemotherapy) between apheresis and infusion was given in 55 percent of patients. The median time from leukapheresis to the start of conditioning chemotherapy was 21 days, and the median time from leukapheresis to axi-cel infusion was 26 days. The median hospitalization period was 14 days.

Safety was evaluable in 274 of the patients receiving Yescarta. Grade 3 cytokine release syndrome occurred in 7 percent of patients and neurological events occurred in 33 percent.

In the 248 patients treated who were evaluable for response at the time of the study cutoff, the overall response rate was 81 percent and the complete response rate was 57 percent.

"This study gave us insight into the real-world outcomes of CAR-T cell therapy for lymphoma," says Dr. Lin, the director of the CAR-T Cell Therapy Program and a member of the U.S. lymphoma CAR-T consortium steering committee. "This multicenter, retrospective study delineates the real-world outcomes of axi-cel CAR-T cell therapy for relapsed or refractory aggressive B-cell lymphoma when used as a standard of care.

"Though limited by relatively short follow-up, it is encouraging to see that the 30-day responses in the real-world setting are comparable to the best responses observed in the ZUMA-1 clinical trial and safety appears comparable despite the fact that nearly half of the patients would have failed to meet ZUMA-1 eligibility criteria."

For more information

CAR-T Cell Therapy Program. Mayo Clinic.

Nastoupil LJ, et al. Axicabtagene ciloleucel (axi-cel) CD19 chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory large B-cell lymphoma: Real world experience. Blood. 2018;132:91.

Neelapu SS, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. New England Journal of Medicine. 2017;377:2531.

Locke FL, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): A single-arm, multicentre, phase 1-2 trial. The Lancet Oncology. 2019;20:31.