ELARA Trial Update: Tisa-Cel Continues to Show Efficacy, Safety in Follicular Lymphoma

Tisagenlecleucel (tisa-cel) continues to demonstrate durable efficacy and favorable safety in patients with relapsed or refractory follicular lymphoma (FL), according to an updated analysis of the phase II ELARA trial published in Blood.

Martin Dreyling, MD, of the Ludwig-Maximilian-University Hospital in Munich, Germany, and colleagues reported longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after a median follow-up of 29 months.

The study included 97 patients who had at least two prior lines of therapy or relapsed after autologous hematopoietic stem cell transplantation. Following lymphodepleting chemotherapy, patients received a single dose of tisa-cel at 0.6 × 10⁸ to 6.0 × 10⁸ chimeric antigen receptor (CAR)–positive viable T-cells.

The median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached, while the estimated 24-month PFS, DOR, and OS rates were 57.4% (95% CI, 46.2-67.0), 66.4% (95% CI, 54.3-76.0), and 87.7% (95% CI, 78.3-93.2), respectively. The complete response rate was 68.1% (95% CI, 57.7-77.3), and the overall response rate was 86.2% (95% CI, 77.5-92.4).

Dr. Dreyling and colleagues also explored the association between baseline clinical and disease factors, blood soluble biomarkers, the tumor microenvironment, and circulating blood cells with clinical response and PFS.

Higher tumor burden at baseline was associated with shorter PFS (P = 0.00016) and DOR (P < 0.0001). Meanwhile, lower levels of tumor-infiltrating LAG3+ exhausted T-cells in the tumor microenvironment were associated with longer PFS and DOR. Lower tumor necrosis factor α and interleukin-10 levels were also associated with longer PFS.

“These data suggest that a preexisting immunosuppressive environment before infusion may hinder effective antitumor function of CAR-T cells,” wrote Dr. Dreyling and colleagues.

The researchers did not observe any new safety signals or treatment-related deaths since the primary analysis. Infection of any grade occurred in 16 (16.5%) patients after transfusion, while grade 3 or higher infection occurred in nine (9.3%) patients. Grade 3 or higher cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in ≤1% of patients.

Two patients developed serious neurological events eight weeks after treatment. All other neurological events resolved at the time of data cutoff.

Relapse occurred in 25 (31%) responders, with a median time to relapse of 121.5 days.

“Long-term efficacy in these patients supports use of [tisa-cel] in a broad population of patients with [relapsed or refractory] FL,” wrote Dr. Dreyling and colleagues. “Long-term follow-up and real-world data are needed to help identify the optimal sequencing for these patients.”

Reference

Dreyling M, Fowler NH, Dickinson M, et al. Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update. Blood. 2024;143(17):1713–1725. doi.org/10.1182/blood.2023021567