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


Axicabtagene ciloleucel (Yescarta) approved for patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy.

The FDA has granted approval to axicabtagene ciloleucel (axi-cel; Yescarta) for the treatment of adult patients with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy.

The approval was based on results of the phase 3 ZUMA-7 trial (NCT03391466), which found that at a median follow-up of 24.9 months, estimated median event-free survival (EFS) was 8.3 months (95% CI, 4.5-15.8) with axi-cel compared with 2.0 months (95% CI, 1.6-2.8) with standard-of-care (SOC) treatment (HR, 0.4-; 95% CI, 0.31-0.51; < .0001). Estimated 18-month EFS rates in the investigative and control cohorts were 41.5% (95% CI, 34.2%-48.6%) and 17.0% (95% CI, 11.8%-23.0%), respectively.

“[The] FDA approval brings that hope to more patients by enabling the power of CAR T-cell therapy to be used earlier in the treatment journey,” said Christi Shaw, chief executive officer of Kite, in a press release. “This milestone has been years in the making. On behalf of the entire Kite community, we would like to thank the patients and physicians who have been on this journey with us. You are what drives us every day to explore the full potential of cell therapy.”

The CAR T-cell therapy was also shown to improve objective response rate (ORR) versus SOC, at 83% (95% CI, 77%-88%) compared with 50% (95% CI, 43%-58%), respectively (odds ratio, 5.31; 95% CI, 3.1-8.9; P < .0001). In the investigative cohort, ORR was comprised of a 65% complete response (CR) rate and a 18% partial response (PR) rate compared with 32% and 18%, respectively, in the SOC cohort.

ZUMA-7, a randomized, international, multicenter, phase 3 trial, evaluated the safety and efficacy of second-line axi-cel with current SOC as second-line treatment in patients with relapsed or refractory LBCL. Eligibility requirements for inclusion in the trial included being at least 18 years of age, having LBCL that was relapsed or refractory within 1 year of frontline treatment, and intention to proceed to consolidation high-dose therapy–autologous stem cell transplant (HDT-ASCT).

The trial enrolled 359 patients randomized 1:1 to receive either a single infusion of axi-cel (n = 180) or SOC in the form of investigator-chosen platinum-based chemoimmunotherapy (n = 179) as second-line treatment. The age of the study participants ranged from 22 years to 81 years, with 30% of patients 65 years of age or older.

An initial disease assessment was performed at day 50, with patients in the axi-cel cohort continuing to day 100, day 150, and long-term follow-up. Patients who responded to treatment with SOC, either with a CR or PR went on to HDT-ASCT. Nonresponders received an additional treatment off trial protocol.

The primary end point of the trial was EFS per blinded central review, with key secondary end points that included ORR, overall survival, progression-free survival, patient-reported outcomes, and safety.

Patients were enrolled between January 25, 2018, and October 4, 2019. The data cutoff date was March 18, 2021, for the EFS primary analysis, at which point 250 events were reported. Among 180 patients randomized to the investigative cohort, 94% were administered axi-cel. Among patients in the SOC cohort, 35% received on-protocol HSCT, and lack of response to chemotherapy was the most common reason for not receiving autologous HSCT. The trial found that 2.5 times more patients administered axi-cel (40.5%) were alive at 2 years without disease progression or the need for additional cancer therapy following a 1-time infusion of axi-cel compared with SOC (16.3%).

Axi-cel is also being evaluated by global regulatory authorities for additional indications inclusive of the ZUMA-7 patient population.

“The ZUMA-7 trial enabled us to look at the broader picture of what happens to patients after a decision is made to follow a particular treatment path,” said Frederick L. Locke, MD, ZUMA-7 principal investigator and co-leader of the Immuno-Oncology Program at Moffitt Cancer Center, in a statement. “What we found was that axi-cel resulted in three times as many patients receiving treatment with curative intent (CAR T-cell therapy), and an overall better outcome for patients than the previous standard of care. Additionally, we have now amassed significant experience with CAR T-cell therapy to better manage or prevent side-effects, making this treatment more accessible for older patients and those with medical conditions for whom the standard of care might be difficult.”


Yescarta® Receives U.S. FDA Approval as First CAR T-cell Therapy for Initial Treatment of Relapsed or Refractory Large B-cell Lymphoma (LBCL). Gilead. [news release]. April 4, 2022. https://www.businesswire.com/news/home/20220401005519/en/

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