Tisagenlecleucel was deemed safe and effective for patients with relapsed/refractory follicular lymphoma (FL) based on the primary analysis of the ELARA trial, which was published in Nature Medicine.

The phase 2 trial (ClinicalTrials.gov Identifier: NCT03568461) was designed to evaluate the safety and efficacy of the chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel.  

The trial enrolled 98 adults with grade 1-3A FL who previously received 2 or more lines of therapy or who relapsed after autologous stem cell transplant. Approximately 64% of patients had bulky disease, 85.6% had stage III-IV disease, and 78.4% were refractory to their prior treatment.


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Ultimately, 97 patients received tisagenlecleucel, 18% of them in an outpatient setting. Most patients (n=93) received the protocol-specified dose (0.6×108 to 6.0×108 CAR+ viable T cells), and 4 patients received a lower dose (0.1×108 to 0.46×108).

Results

The median follow-up was 16.6 months for the 97 infused patients and 16.9 months for the 94 patients who were evaluable for efficacy.

The complete response rate (CRR) was 69.1%, and the overall response rate (ORR) was 86.2%, according to an independent review committee. The researchers noted that CRRs were comparable across subgroups, including in patients with high-risk features.

There were 31 patients who initially had a partial response at 3 months, and 15 of them later converted to a complete response. At the last evaluation before the data cutoff, 65 patients (69.1%) had an ongoing response.

The median duration of response, progression-free survival (PFS), overall survival, and time to next treatment were not reached. The PFS rate at 12 months was 67% for the entire cohort and 85.5% among complete responders.

Cellular kinetics analyses showed CAR transgene persistence for up to 558 days in responders and 366 days in nonresponders.

Among the 97 patients evaluable for safety, 99% experienced any-grade adverse events (AEs). At least 1 grade 3 or higher AE was observed in 78.4% of patients, and the most common of these was neutropenia (42.3%). Treatment-related AEs of any grade occurred in 78.4% of patients, and grade 3 or higher treatment-related AEs were seen in 46%.

Within 8 weeks of infusion, cytokine release syndrome (CRS) occurred in 48.5% of patients. All cases of CRS were grade 1-2. The median time to onset and resolution of CRS was 4 days. CRS treatments included tocilizumab (34%) and steroids (6.4%).

Neurological events occurred in 37.1% of patients, and 4.1% had immune effector cell-associated neurotoxicity syndrome (ICANS). Three patients had grade 3 or higher neurological events, and 1 patient had grade 3 or higher ICANS. There were 7 deaths on study, but none were considered treatment-related.

“Along with the possibility of outpatient treatment with tisagenlecleucel, the efficacy and safety data from the ELARA study… are promising and will need to be evaluated for potential long-term benefits through studies with longer follow-up,” the researchers concluded.

Disclosures: This research was supported by Novartis Pharmaceuticals Corporation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Fowler NH, Dickinson M, Dreyling M, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: The phase 2 ELARA trial. Nat Med. Published online December 17, 2021. doi:10.1038/s41591-021-01622-0