Tisagenlecleucel Effective, Safe in Relapsed or Refractory Follicular Lymphoma

An interim analysis of the phase II ELARA trial found tisagenlecleucel to be effective and safe for the management of pretreated, relapsed or refractory follicular lymphoma (FL). The analysis was recently published in Nature Medicine.

Tisagenlecleucel is an autologous CD19-directed chimeric antigen receptor T-cell therapy. It has already been approved by the US Food and Drug Administration for use in adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), high-grade B-cell lymphoma and DLBCL that has developed from FL, and relapsed or refractory B‐cell precursor acute lymphoblastic leukemia in patients aged up to 25 years.

The patient cohort in the multinational ELARA trial included 98 adults with relapsed or refractory FL, all of whom had already undergone at least two lines of treatment or experienced relapse after autologous stem cell transplant. The patients had undergone a median of four previous treatments, but a majority of the cohort was naïve to lenalidomide, lenalidomide plus rituximab, and phosphatidylinositol 3-kinase inhibitor therapies. Ninety-seven of the enrolled patients had received tisagenlecleucel as of March 2021, and they had a median treatment follow-up of 16.59 months.

The efficacy set of the trial comprised 94 patients. This cohort achieved a complete response (CR) rate of 69.1%, an overall response rate of 86.2%, and a progression-free survival (PFS) rate at 12 months of 67.0%. For the patients who achieved CR, the analysis estimated a duration of response rate at nine months of 86.5% and a PFS rate at 12 months of 85.5%.

“Antitumor activity was seen independently of established risk factors for progression and across subgroups of patients,” noted lead analysis author Nathan Hale Fowler, MD, of the MD Anderson Cancer Center. These factors included having advanced or bulky disease, a high Follicular Lymphoma International Prognostic Index score, progression of disease within 24 months, and disease refractory to more than two lines of therapy.

There were seven mortalities among the 97 patients who formed the safety set in the trial, but none were related to treatment. Within eight weeks of infusion there was a 48.5% cytokine release syndrome rate, but all of the occurrences were below grade 3. The set had a neurological event rate of 37.1%, with the rate specifically for events of grade 3 or higher calculated to be 3.0%. The rate of immune effector cell-associated neurotoxicity syndrome in the set was 4.1%, with the rate specifically for events of grade 3 or higher calculated to be 1.0%.

“Along with the possibility of outpatient treatment with tisagenlecleucel, the efficacy and safety data from the ELARA study in heavily pretreated patients with [relapsed or refractory] 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,” said Dr. Fowler of the interim analysis findings.

Reference

Fowler NH, Dickinson M, Dreyling M, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med. 2022;28(2):325-332. doi:10.1038/s41591-021-01622-0