CAR T-Cell Therapy Earns Indication for Lymphoma in First Relapse

The FDA approved the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel, Yescarta) as initial treatment for relapsed/refractory large B-cell lymphoma (LBCL).

The action moves CAR T-cell therapy to the earliest approved line of treatment since the class reached the marketplace almost 5 years ago. The approval includes patients with LBCL that has proven refractory to first-line chemoimmunotherapy or has relapsed within 12 months of first-line chemoimmunotherapy. The treatment is not indicated for patients with primary central nervous system lymphoma.

The approval follows the National Comprehensive Cancer Network category 1 recommendation for axi-cel in primary refractory diffuse large B-cell lymphoma or disease that has relapsed within 12 months after initial treatment.

Support for earlier use of the therapy came from the ZUMA-7 trial, which showed a greater than two-fold improvement in 24-month event-free survival (EFS) for patients who received second-line axi-cel. The difference represented a 60% reduction in the EFS hazard compared with standard-of-care chemoimmunotherapy (P<0.0001). Axi-cel led to a median EFS of 8.3 months versus 2.0 months with standard of care.

“Today’s approval marks an exciting new standard of care,” said Frederick Locke, MD, of Moffitt Cancer Center in Tampa, Florida, in a statement from Kite Pharma. “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. What we found was that axi-cel resulted in three times as many patients receiving treatment with curative intent 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,” he added.

“Definitive clinical trial results such as these do not come along often and should drive a paradigm shift in how patients with relapsed or refractory LBCL are treated moving forward,” noted Jason Westin, MD, of the University of Texas MD Anderson Cancer Center in Houston. “Patients who do not respond to or relapse after initial treatment should quickly be referred to a CAR T-cell therapy authorized treatment center for evaluation.”

The FDA has required a boxed warning about the risk of cytokine release syndrome (CRS) and neurologic toxicity associated with axi-cel. In clinical studies, more than 90% of patients treated with the therapy developed CRS, which was grade 1/2 severity in most cases. Neurologic toxicity occurred in 70% to 80% of patients and reached grade 3 severity in 25% to 30% of cases.