Tisagenlecleucel (tisa-cel) did not improve event-free survival (EFS) compared with second-line standard of care (SOC) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to results from the phase 3 BELINDA trial.
The results were presented at the 2021 American Society of Hematology (ASH) Annual Meeting and published in The New England Journal of Medicine.1,2
The BELINDA trial (ClinicalTrials.gov Identifier: NCT03570892) included 322 patients with aggressive NHL who had relapsed or refractory disease within 12 months of first-line therapy.
The patients were randomly assigned to receive tisa-cel with optional bridging therapy (162 patients) or SOC (160 patients). SOC consisted of a platinum-based chemotherapy regimen, followed by autologous hematopoietic stem cell transplant (auto-HSCT) in responders or a second platinum-based chemotherapy regimen in nonresponders.
There was a slight imbalance in baseline characteristics between the 2 arms. Patients in the tisa-cel arm were more likely to have high-grade B-cell lymphoma (24% vs 17%) and an international prognostic index of 2 or higher (65% vs 58%).
In the tisa-cel arm, 17% of patients did not receive any bridging therapy, 36% received 1 cycle, and 48% received 2 or more cycles of bridging therapy or a second platinum-based chemotherapy regimen.
In the SOC arm, 99% of patients received 1 or more cycles of platinum-based chemotherapy, including 54% of patients who received a second platinum-based chemotherapy regimen.
About 96% of patients in the tisa-cel arm received a single infusion of tisa-cel, and 33% of patients in the SOC arm underwent auto-HSCT. In the SOC arm, 81 patients crossed over to receive tisa-cel.
The median follow-up was 10 months (range, 2.9-23.2 months).
The median EFS was 3 months in both treatment arms (hazard ratio, 1.07; 95% CI, 0.82-1.40; P =.69).
At 6 weeks, the overall response rate (ORR) was 38% in the tisa-cel arm and 54% in the SOC arm. The complete response (CR) rate was 11% and 19%, respectively.
The best ORR, at or after 12 weeks, was 46% in the tisa-cel arm and 43% in the SOC arm. The CR rate was 28% in both arms.
Six patients responded to tisa-cel but were counted as an event in the EFS analysis due to having stable disease or progressive disease soon after infusion.
Grade 3 or higher adverse events (AEs) occurred in 84% of patients in the tisa-cel arm and 90% of patients in the SOC arm.
In the tisa-cel arm, 5% of patients had grade 3 or higher cytokine release syndrome, and 2% had grade 3 or higher neurologic events.
There were 52 (32%) deaths in the tisa-cel arm and 45 (28%) in the SOC arm. Most deaths in the tisa-cel arm (n=42) and the SOC arm (n=32) were due to progressive disease. The remaining 10 deaths in the tisa-cel arm and 13 in the SOC arm were a result of AEs.
These results should help guide the optimal use of chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory NHL, according to the researchers. The findings underline the importance of preventing progressive disease prior to CAR T-cell infusion, which suggests that effective bridging therapy and a shorter time to infusion could be key to improving outcomes.
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.
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- Bishop MR, Dickinson M, Purtill D, et al. Tisagenlecleucel vs standard of care as second-line therapy of primary refractory or relapsed aggressive B-cell non-Hodgkin lymphoma: Analysis of the phase III BELINDA study. Presented at ASH 2021; December 11-14, 2021. Abstract LBA6.
- Bishop MR, Dickinson M, Purtill D, et al. Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma. N Engl J Med. Published online December 14, 2021. doi:10.1056/NEJMoa2116596