IBCL-195: Primary Analysis of the Phase 2 ELARA Trial: Tisagenlecleucel Efficacy and Safety in Adult Patients with Relapsed/Refractory Follicular Lymphoma (r/r FL)

Abstract

Context Tisagenlecleucel demonstrated durable responses and manageable safety in adult patients with r/r diffuse large B-cell lymphoma. Objective Determine the efficacy and safety of tisagenlecleucel in adult patients with r/r FL. Design ELARA (NCT03568461) is an international, multicenter, single-arm, phase 2 trial of tisagenlecleucel treatment. Patients or Other Participants Adult (≥18 years) patients with r/r FL (grades 1–3A) after ≥2 lines of therapy or whose disease relapsed after autologous stem cell transplant were eligible. As of September 28, 2020, 98 patients were enrolled. Interventions Bridging therapy was permitted, and disease status was reassessed prior to infusion. Patients received tisagenlecleucel (0.6–6×10 8 CAR+ viable T-cells) after lymphodepleting chemotherapy. Main Outcomes Measures Primary endpoint was complete response rate (CRR) by central review (Lugano 2014 criteria). Secondary endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and cellular kinetics. Results Ninety-seven patients received tisagenlecleucel (median follow-up, 10.6 months). Median age at study entry was 57 years (range, 29-73), 85% had stage III–IV disease, 60% had a FLIPI score ≥3, 65% had bulky disease, and 42% had LDH > upper limit of normal. Median number of prior therapies was 4 (range, 2–13); 78% of patients were refractory to their last treatment, and 60% progressed ≤2 years of initial anti-CD20-containing treatment. Among 94 patients evaluable for efficacy, CRR was 66% (95% CI, 56%–75%), and ORR was 86% (95% CI, 78%–92%). Estimated DOR (CR) and PFS rates at 6 months were 94% (95% CI, 82%–98%) and 76% (95% CI, 65%–84%), respectively. Of 97 patients evaluable for safety, 65% experienced grade ≥3 adverse events ≤8 weeks post-infusion, most commonly neutropenia (28%) and anemia (13%). Any-grade cytokine release syndrome (Lee scale) occurred in 49% of patients. Any-grade neurological events (per CTCAE v4.03) occurred in 9% of patients. Three patients died from disease progression. C(max) and AUC(0–28d) for tisagenlecleucel were similar between responders and nonresponders. C(max) was achieved at a median of 10 days in responders and 12.9 days in nonresponders. Conclusions Tisagenlecleucel demonstrated efficacy and a favorable safety profile in patients with r/r FL. The study was funded by Novartis.