Accelerated Approval Granted to Tisagenlecleucel for Treatment of Relapsed or Refractory Follicular Lymphoma

Follicular lymphoma cells.

The FDA has given accelerated approval to tisagenlecleucel (Kymriah®, Novartis) for treatment of patients with relapsed or refractory (R/R) follicular lymphoma (FL) within six months of receiving two or more lines of systemic therapy or if the patient relapsed after an autologous hematopoietic stem cell transplant.

“Follicular lymphoma is a common non-Hodgkin lymphoma that is generally considered indolent, but the disease remains incurable, and the majority of patients eventually relapse,” wrote Nathan Hale Fowler, MD, Professor of Medicine at MD Anderson Cancer Center, and colleagues, in their published results of the ELARA trial (NCT03568461), on which the approval was based. “Patients with R/R FL will experience progressively shorter duration of response to subsequent treatments (second or later lines of therapy) as reflected by progression-free survival, which has been shown to decrease from 6.6 years after the first line of therapy to 1.5 years and 10 months after the second and third lines of therapy, respectively.”

In this phase 2, open-label, single-arm trial, 97 patients were enrolled to receive tisagenlecleucel as a single intravenous infusion (IV); 93 patients received the protocol-specified dosage of 0.6 to 6.0 x 108 chimeric antigen receptor (CAR)-positive viable T cells, and four patients received a lower dosage between 0.1 × 108 and 0.46 × 108 CAR T cells. The primary end point was complete response rate, based on Lugano classification response criteria for best response determined by an independent review committee. Key secondary end points included overall response rate, duration of response, progression free survival, and overall survival.

At a median follow-up of 9.9 months, positive results were reported at the primary, prespecified interim endpoint with complete response rate being achieved in 69% of patients. Further promise was seen with 86% of patients achieving an overall response rate. The median duration of response, progression free survival, and overall survival were not reached. At the nine-month mark among patients who received a complete response, duration of response was estimated 87%, and at the 12-month progression free survival was estimated 86%. The overall population at the 12-month mark rate for progression free survival was 67%.

The most common adverse reactions occurring in >20% of patients were cytokine release syndrome, infection, fatigue, musculoskeletal pain, headache, and diarrhea.

“The primary analysis results from ELARA demonstrate that tisagenlecleucel is an effective therapy with a manageable safety profile for a R/R FL patient population after two or more lines of therapy with limited treatment options and an unfavorable prognosis,” concluded Dr. Howler and colleagues in their report. “Along with the possibility of outpatient treatment with tisagenlecleucel, the efficacy and safety data from the ELARA study in heavily pretreated patients with R/R FL, including those with high-risk disease characteristics, are promising and will need to be evaluated for potential long-term benefits through studies with longer follow-up.”

The recommended tisagenlecleucel dosage for adult patients with R/R FL is a single IV of 0.6 to 6.0 x 108 CAR-positive viable T cells. Tisagenlecleucel is only available through a Risk Evaluation and Mitigation Strategy (REMS) program.

For More Information

Fowler NH, Dickinson M, Dreyling M, et al (2022). Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med, 28(2):325-332. DOI:10.1038/s41591-021-01622-0 (2022). Efficacy and safety of tisagenlecleucel in adult patients with refractory or relapsed follicular lymphoma (ELARA). NLM identifier: NCT03568461.

Kymriah® (tisagenlecleucel) prescribing information (2022). Novartis. Available at:

US Food and Drug Administration (2022). FDA approves tisagenlecleucel for relapsed or refractory follicular lymphoma. Available at:

Image Credit: Patho. Licensed under CC BY-SA 3.0

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