On May 28, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah) for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. Tisagenlecleucel is now FDA-approved in three indications and remains the only CAR T-cell therapy approved in both adult and pediatric settings.
ELARA Trial
The approval is based on data from the phase II ELARA trial (ClinicalTrials.gov identifier: NCT03568461), a single-arm, open-label trial, in which 90 patients were evaluated for efficacy with a median follow-up of approximately 17 months.
Eighty-six percent of patients treated with tisagenlecleucel achieved a response, including 68% who experienced a complete response. Prolonged durable response to treatment was demonstrated, with an estimated 85% of patients who achieved a complete response still in response 12 months after initial response. Tisagenlecleucel was shown to be effective in high-risk patients, including those who were heavily pretreated or had refractory disease, POD24, bulky disease, or those with high Follicular Lymphoma International Prognostic Index (FLIPI) scores.
For the 97 patients evaluable for safety at a median follow-up of 21 months, 53% experienced any-grade cytokine-release syndrome (as defined by the Lee scale), and there were no reported cases of high-grade (grade 3 or higher) cytokine-release syndrome. Forty-three percent of patients experienced any-grade neurologic events; grade 3 or higher neurologic events were seen in only 6% of patients. Eighteen percent of patients were infused in an outpatient setting.
Stephen J. Schuster, MD
“Patients with follicular lymphoma who relapse or don’t respond to treatment have a poor prognosis and may face a series of treatment options without a meaningful, lasting response,” said Stephen J. Schuster, MD, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma in the Division of Hematology Oncology, and Director of the Lymphoma Program and Translational Research at the University of Pennsylvania’s Abramson Cancer Center, institutional principal investigator of the ELARA trial. “This new, effective option for patients with follicular lymphoma may offer long-term benefit.”
While follicular lymphoma is typically an indolent type of cancer, patients with follicular lymphoma may be exposed to a median of 4 lines of treatment, with an upper range of 13 lines. Although there are multiple systemic therapies available, the efficacy of these regimens drops off rapidly in later lines.
In early May 2022, the European Commission approved tisagenlecleucel for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.
In accordance with the Accelerated Approval program, continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
