Tisagenlecleucel Granted FDA Priority Review for Relapsed/Refractory Follicular Lymphoma

Patients with relapsed or refractory follicular lymphoma who have received 2 prior lines of therapy appear to benefit from treatment with tisagenlecleucel, which was granted a priority review by the FDA.

The FDA has granted priority review to tisagenlecleucel (Kymriah) for adult patients with relapsed or refractory follicular lymphoma who have undergone 2 previous lines of treatment, according to a press release from therapy developer Novartis.1

Submissions to the regulatory organization were based on findings from the phase 2 ELARA trial (NCT03568461), results of which were presented at the 2021 American Society of Clinical Oncology Annual Meeting.2 Treatment with the CD19-targeting CAR T-cell therapy resulted in an overall response rate of 86%, including a complete response (CR) rate of 66%. After 11 months of follow-up, the median duration of response was not reached.

“This is an important milestone in our mission to bring Kymriah to adult patients with relapsed or refractory follicular lymphoma. Receiving orphan drug designation from the [European Commission] as well as priority review from the FDA underscores the unmet need and urgency for these patients. With Kymriah demonstrating impressive results in the ELARA trial, we are hopeful that we can offer a unique and potentially definitive treatment that minimizes the burden,” Jeff Legos, executive vice president and global head of Oncology & Hematology Development at Novartis, said in a press release.

The trial enrolled 98 patients, 97 of whom were treated and evaluable for safety. After undergoing lymphodepleting chemotherapy, patients were given a single intravenous infusion of tisagenlecleucel at a dose of 0.6 × 108 CAR-positive T cells.

The median follow-up for efficacy was 10.9 months. Additional findings from the study indicated that the probability for patients continuing to respond to treatment for 6 months or more was 79% (95% CI, 66-87). Moreover, 38.7% of partial responses converted to CRs, with all but 1 conversion occurring between months 3 and 6. Investigators noted that the median time to next anti-lymphoma treatment had not been reached.

Additional findings from the trial indicated that CR rates were consistent across all patient subgroups. Investigators noted that the median progression-free survival (PFS; 95% CI, 12.1-not evaluable [NE]) and overall survival (95% CI, NE-NE) were not reached. The 6-month PFS rate was 76% (95% CI,65%-84%).

In terms of safety, 48.5% of patients experienced any-grade cytokine release syndrome (CRS) and no patients had CRS that was grade 3 or higher. Neurological adverse effects of any grade occurred in 9.3% of patients, with 1.0% experiencing grade 3 or higher events. Notably, all neurological and CRS adverse events resolved with appropriate management.

Tisagenlecleucel was most recently granted a regenerative medicine advanced therapy designation by the FDA in April 2020 for patients with relapsed/refractory follicular lymphoma.

References

  1. Novartis receives priority review by US FDA and filing acceptance by EMA for Kymriah® to treat patients with relapsed or refractory follicular lymphoma. News release. Novartis. October 27, 2021. Accessed October 27, 2021. https://bit.ly/3Gv8skr
  2. Schuster SJ, Dickinson MJ, Dreyling MH, et al. Efficacy and safety of tisagenlecleucel (Tisa-cel) in adult patients (Pts) with relapsed/refractory follicular lymphoma (r/r FL): primary analysis of the phase 2 Elara trial. J Clin Oncol. 2021;39(suppl 15):7508. doi:10.1200/JCO.2021.39.15_suppl.7508