No EFS Benefit With Second-Line Tisa-Cel in Relapsed/Refractory Non-Hodgkin Lymphoma


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 ( Identifier: NCT03570892) included 322 patients with aggressive NHL who had relapsed or refractory disease within 12 months of first-line therapy.

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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%).

Treatment Details

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.

Read more of Cancer Therapy Advisor’s coverage of the ASH 2021 meeting by visiting the conference page.


  1. 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.
  2. 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

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