The US Food and Drug Administration ( FDA ) has granted accelerated approval for Kymriah ( Tisagenlecleucel ) for the treatment of adult patients with relapsed or refractory ( r/r ) follicular lymphoma ( FL ) 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 trial(s).
Kymriah is now FDA approved in three indications and remains the only CAR-T cell therapy approved in both adult and pediatric settings.
The approval is based on data from the phase II ELARA trial, 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 Kymriah 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.
Kymriah was shown to be effective in high-risk patients including those who were heavily pretreated or had refractory disease, progression of disease within 2 years ( POD24 ), bulky disease or those with high FLIPI ( Follicular Lymphoma International Prognostic Index ) scores.
For the 97 patients evaluable for safety at 21 months of median follow-up, the safety profile of Kymriah was remarkable.
Fifty-three percent of patients experienced any-grade cytokine release syndrome ( CRS ), 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 ( 17 of 97 patients ) were infused in an outpatient setting.
While follicular lymphoma is typically an indolent type of cancer, patients with follicular lymphoma may be exposed to a median of four 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. ( Xagena )
Source: Novartis, 2022