Tisa-Cel Yields Superior Efficacy Over SOC in R/R Follicular Lymphoma

Patients with relapsed/refractory follicular lymphoma who were treated with tisagenlecleucel (tisa-cel; Kymriah) experienced a significant improvement in survival outcomes compared with those who received a standard of care (SOC) regimen, according to an indirect treatment comparison of the phase 2 ELARA trial (NCT03568461) and ReCORD-FL trial (NCT04342117) published in Blood Advances.

As this was a single-arm trial, investigators pulled findings from the global, observational, retrospective ReCORD-FL trial to obtain SOC data for a population of patients with relapsed/refractory follicular lymphoma. The complete response rate was 69.1% (95% CI, 59.8%-78.3%) in the tisa-cel arm vs 37.3% (95% CI, 26.4%-48.3%) in the SOC arm, and the overall response rate (ORR) was 85.6% (95% CI, 78.7%-92.5%) vs 63.6% (95% CI, 52.5%-74.7%). At 12 months, the probability of being progression free or event free was 70.5% (95% CI, 61.4%-79.7%) in the tisa-cel arm vs 51.9% (95% CI, 40.6%-63.3%) in the SOC arm (HR, 0.60; 95% CI, 0.34-0.86). Additionally, probability of overall survival at 12 months was 96.6% (95% CI, 92.9%-100%) in the tisa-cel arm vs. 71.7% (95% CI, 61.2%-82.2%) in the SOC arm (HR, 0.2; 95% CI, 0.02-0.38).

“This study provides further context to the results of the single-arm ELARA trial by providing needed historical control data from clinically similar patients receiving usual care in routine practice settings. The ITC [indirect treatment comparison] results suggest that tisa-cel has superior efficacy over usual care in a clinically similar, matched group of patients with [relapsed/refractory follicular lymphoma] for all evaluated endpoints. Taken together, findings presented here provide a key benchmark and suggest that tisa-cell may be a valuable treatment option for consideration in patients with multiply [relapsed/refractory follicular lymphoma,” concluded the investigators.

The median number of lines of previous therapy was 4 and 37% of patients received prior autologous hematopoietic stem cell transplant. For patients who received SOC, the most common treatment regimens consisted of anti-CD20 monoclonal antibody plus alkylator (31.5%), anti-CD20 monoclonal antibody minus alkylator (25.9%), alkylator without anti-CD20 monoclonal antibody (17.5%), and other regimens (25.2%).

Prior to the indirect treatment comparison analysis which included ELARA and the ReCORD-FL for the SOC patients, anti-CD20 monoclonal antibody plus an alkylator was given. Other treatments given to those in the ReCORD-FL and ELARA trial included PI3K inhibitors (14.0% vs 21.4%), lenalidomide alone or in combination with other treatments (15.4% vs 22.4%), and lenalidomide plus rituximab (9.8% vs 17.3%).

The progression-free survival and event-free survival was not reached (NR) in the tisa-cel arm but was 13.1 months (95% CI, 8.1-NR) in the SOC arm; this was indicative of a 40% reduction in the risk of progression, death, or starting a new anti-cancer therapy at 12 months in the tisa-cel arm compared with the SOC arm.

In the sub-analysis, which included usual care patients with lines of therapy that started at or beyond 2014, the complete response rate in the tisa-cel arm remained superior with 69.1% vs 30.5% in the SOC arm and the ORRs were 85.6% and 58.8%, respectively. The population size was significantly lower in the analysis with 37 patients compared with 95 in the actual sample size, which highlighted a greater loss of statistical precision in the sub-analysis while in the main analysis, which had sample sizes of 99 and 95 patients, respectively. All end point differences were statistically significant.

Reference

Salles GA, Schuster SJ, Dreyling M, et al. Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma. Blood Adv. Published online August 16, 2022. doi:10.1182/bloodadvances.2022008150