Tisagenlecleucel is safe and effective for adults with pretreated relapsed/refractory follicular lymphoma (FL).

  • Major Finding: Tisagenlecleucel is safe and effective for adults with pretreated relapsed/refractory follicular lymphoma (FL).

  • Concept: Cytokine release syndrome and neurologic events were observed with no treatment-related deaths.

  • Impact: Tisagenlecleucel shows promising safety and efficacy in FL, supporting further investigation of long-term benefits.


Patients with follicular lymphoma (FL), a common type of non-Hodgkin lymphoma, often relapse on chemoimmunotherapy treatments. Those who experience progression of disease within 2 years of initial treatment have a particularly poor prognosis with even shorter duration of response to subsequent treatments. Additional treatments for relapsed/refractory FL, including PI3K inhibitors, lenalidomide combined with rituximab, and EZH2 inhibitors, have been developed but show only modest efficacy. In a small pilot study using tisagenlecleucel, an anti-CD19 chimeric antigen receptor T-cell therapy that has been previously approved for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, led to complete responses in 71% of patients with relapsed/refractory FL after a median follow-up of over 5 years. Fowler and colleagues reported the prespecified interim analysis of the phase II trial (ELARA) of tisagenlecleucel infusion in 97 adult patients with relapsed/refractory FL after two or more lines of previous therapy or autologous stem cell transplant. The primary endpoint of complete response rate was met (69.1%). A partial response at 3 months was observed in 31 patients, with 15 of these patients eventually converting to a complete response. Secondary endpoints included overall response rate (ORR) and safety: The ORR was 86.2%, and treatment-related adverse events were reported in 96.9% patients, with 71% reporting grade 3 or 4 events within 8 weeks of infusion. Cytokine release syndrome was observed in 49% of patients, 37.1% of patients demonstrated neurologic events, and 4.1% of patients developed immune effector cell–associated neurotoxicity syndrome. No treatment-related deaths were reported. Overall, this trial indicates safety and efficacy of tisagenlecleucel in heavily pretreated adult patients with relapsed/refractory FL, with longer follow-up needed to analyze other secondary endpoints of duration of response, progression-free survival, and overall survival.

Fowler NH, Dickinson M, Dreyling M, Martinez-Lopez J, Kolstad A, Butler J, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med 2021 Dec 17 [Epub ahead of print].

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