Axicabtagene Ciloleucel Approved for Second-Line Treatment of Large B-Cell Lymphoma

Large B-cell lymphoma cells.

The FDA has approved axicabtagene ciloleucel (Yescarta®, Kite Pharma, Inc.) for treatment of adult patients with large B-cell lymphoma (LBCL). Axicabtagene ciloleucel, also known as axi-cel, is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. It is indicated as a second-line treatment for patients who have already undergone first-line chemoimmunotherapy with no response or who have experienced relapse within 12 months of first-line chemoimmunotherapy. It is noted that axicabtagene ciloleucel is not to be used for treatment of patients with primary central nervous system lymphoma.

“For patients with relapsed or refractory large B-cell lymphoma after first-line chemoimmunothrapy, standard second-line treatment includes salvage chemoimmunotherapy and, for patients with a response, high-dose chemotherapy with autologous stem-cell transplantation, but the prognosis for many is poor,” wrote Frederick L. Locke, MD, Co-Leader of the Immuno-Oncology Program at Moffitt Cancer Center, and colleagues, in their published results of the ZUMA-7 clinical trial (NCT03391466), on which the approval was based. “Axi-cel therapy lead to significant improvements, as compared with standard care, in event-free survival and response, with expected levels of high-grade toxic effects.”

The phase 3, open-label, international, multicenter trial enrolled 359 patients with LBCL who had undergone first-line chemoimmunotherapy with no response or who relapsed within 12 months of receiving chemoimmunotherapy. Patients were randomized in a 1:1 ratio to receive either a single infusion of axicabtagene ciloleucel or standard care. Patients receiving axicabtagene ciloleucel underwent leukapheresis, followed by 500 mg/m2 of body surface area per day of cyclophosphamide and 30 mg/m2 of body-surface area per day of fludarabine on days five, four, and three prior to infusion. Bridging therapy with glucocorticoids was permitted. The target dose of axicabtagene ciloleucel was 2×10­­­­­6 CAR T cells per kg of body weight. Patients in the standard care group underwent two to three cycles of chemoimmunotherapy, with those experiencing a complete or partial response going on to receive high-dose chemotherapy and autologous stem cell transplantation. The primary end point of the trial was event-free survival, followed by key secondary end points of response and overall survival.

At a median follow-up of 24.9 months, axicabtagene ciloleucel produced a significantly longer event-free survival rate (8.3 months) in comparison with those receiving standard care (2.0 months). At the 18-month mark, the estimated event-free survival rate was significantly improved in those receiving axicabtagene ciloleucel (41.5%) compared with those receiving standard care (17.0%). Furthermore, the secondary end point of response rate in those receiving axicabtagene ciloleucel was 1.66 times higher than those receiving standard care (83% vs 50%). Overall survival was not reached in the axicabtagene ciloleucel group, compared with 35.1 months in the standard care group.

Adverse reactions experienced by ≥30% of patients who received axicabtagene ciloleucel were cytokine release syndrome (CRS), fever, hypotension, fatigue, anemia, diarrhea, headache, nausea, tachycardia, headache, nausea, tachycardia, and leukopenia. Axicabtagene ciloleucel is noted with a boxed warning for patients with non-Hodgkin lymphoma; studies revealed occurrences of CRS in 88% and neurologic toxicities in 81%. Axicabtagene ciloleucel is only available under a Risk Evaluation and Mitigation Strategy (REMS) program.

“The ZUMA-7 trial showed a significant improvement in efficacy with axi-cel therapy as compared with second-line standard care, in patients with relapsed or refractory large B-cell lymphoma,” concluded Dr. Locke and colleagues, in their report. “Axi-cel appears to be a viable alternative to a regimen of chemoimmunotherapy, high-dose chemotherapy, and autologous stem-cell transplantation for the second-line treatment of relapsed or refractory large B-cell lymphoma.”

The recommended dosage of axicabtagene ciloleucel is 2×106 CAR-positive viable T cells per kg of body weight, with a maximum of 2×108 CAR-positive viable T cells.

For More Information:

Locke FL, Miklos DB, Jacobson CA, et al (2022). Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med, 386:640-654. DOI:10.1056/NEJMoa2116133. (2022). Efficacy of axicabtagene ciloleucel compared to standard of care therapy in subjects with relapsed/refractory diffuse large B cell lymphoma (ZUMA-7). NLM identifier: NCT03391466.

Yescarta® (axicabtagene ciloleucel) prescribing information (2022). Kite Pharma, Inc. Available at:

US Food and Drug Administration (2022). FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. Available at: 

Image Credit: Nephron. Licensed under CC BY-SA 3.0

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