Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial

Abstract

Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor-T cell therapy with clinically meaningful outcomes demonstrated in patients with relapsed/refractory (r/r) B-cell lymphoma. In a previous pilot study of tisagenlecleucel in r/r follicular lymphoma (FL), 71% of patients achieved a complete response (CR). Here we report the primary, prespecified interim analysis of the ELARA phase 2 multinational trial of tisagenlecleucel in adults with r/r FL after two or more treatment lines or who relapsed after autologous stem cell transplant (no. NCT03568461). The primary endpoint was CR rate (CRR). Secondary endpoints included overall response rate (ORR), duration of response, progression-free survival, overall survival, pharmacokinetics and safety. As of 29 March 2021, 97/98 enrolled patients received tisagenlecleucel (median follow-up, 16.59 months; interquartile range, 13.8-20.21). The primary endpoint was met. In the efficacy set (n = 94), CRR was 69.1% (95% confidence interval, 58.8-78.3) and ORR 86.2% (95% confidence interval, 77.5-92.4). Within 8 weeks of infusion, rates of cytokine release syndrome were 48.5% (grade ≥3, 0%), neurological events 37.1% (grade ≥3, 3%) and immune effector cell-associated neurotoxicity syndrome (ICANS) 4.1% (grade ≥3, 1%) in the safety set (n = 97), with no treatment-related deaths. Tisagenlecleucel is safe and effective in extensively pretreated r/r FL, including in high-risk patients.

A Retrospective Cohort Study of Treatment Outcomes of Adult Patients With Relapsed or Refractory Follicular Lymphoma (ReCORD-FL)

“…13 Results from ELARA indicate high and durable efficacy of tisa-cel in r/r FL, where 69% of patients achieved complete remission and 76% maintained response for at least 9 months. 13…”

A Multi-scale, Multiomic Atlas of Human Normal and Follicular Lymphoma Lymph Nodes

“…The co-expression of markers associated with cytolytic activity and immune inhibition suggests the presence of an anti-FL response that might be re-invigorated for therapeutic purposes. Although initial efforts using T-cell directed cell therapies in FL have shown great promise, including among high-risk patients, mechanisms of immune evasion and resistance remain largely unknown (Fowler et al, 2022).…”

Targeted Agents in the Treatment of Indolent B-Cell Non-Hodgkin Lymphomas

“…Targeted immunotherapeutics have expanded dramatically over the last two decades and the full spectrum is beyond the scope of this review. Most promising amongst the novel approaches in this domain are chimeric antigen receptor T-cells (CAR-T), CAR-NK cells and bispecific T-cell recruiting antibodies, all with emerging evidence for use in the indolent lymphomas, particularly FL [ 141 , 142 , 143 , 144 , 145 ]. Expanded investigation into WM/LPL, MZL and other indolent forms is awaited.…”

“…Tisagenlecleucel, a second CD19 CAR T, has also recently been investigated in the phase 2 ELARA study and is awaiting expedited FDA review ( Table 5 ) [ 145 ]. Results from 97 infused patients with R/R FL demonstrated similar ORR of 86.2%, CRR of 69.1% with lower rates of high-grade CRS (0%) and neurotoxicity (1%) in keeping with tisagenlecleucel’s more favourable safety profile in DLBCL.…”