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Comparing Tisa-Cel to Standard of Care in Relapsed/Refractory Aggressive B-Cell NHL

January 13, 2022

The autologous CD19-targeting chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (tisa-cel) is a second-line treatment for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (NHL). Its use led to noninferior event-free survival (EFS) compared with standard platinum-based chemotherapy (PCT) followed by autologous hematopoietic cell transplantation (autoHCT), according to a late-breaking abstract presentation at the 2021 ASH Annual Meeting.

Currently, tisa-cel is approved by the U.S. Food and Drug Administration for the treatment of patients with large B-cell lymphoma who have received two or more prior lines of therapy. In the phase III BELINDA trial, researchers led by Michael R. Bishop, MD, of the David and Etta Jonas Center for Cellular Therapy at the University of Chicago, compared tisa-cel with the current standard of care as a second-line treatment in adult patients with relapsed/refractory B-cell NHL.

After undergoing leukapheresis for tisa-cel production, 322 patients were randomized to receive either:

  • tisa-cel (arm A; n=162)
  • standard of care (arm B; n=160)

Patients were then stratified by duration of response to previous chemoimmunotherapy, International Prognostic Index (IPI), and geographic region. In arm A, 33% of patients were 65 years of age or older, compared with 29% of patients in arm B. Primary refractory disease was reported in 66% and 67% of patients in arms A and B, respectively. More patients had high-grade B-cell lymphomas (24% vs. 17%) and IPI ≥2 (65% vs. 58%) in arm A than in arm B.

Patients in arm A received investigator’s choice of protocol-defined PCT regimens as optional bridging therapy, followed by lymphodepletion and a single infusion of tisa-cel (0.6-6×108 CAR T cells). In arm B, patients received investigator’s choice of PCT regimen followed by either autoHCT for those whose disease responded to the treatment or second PCT for those whose disease did not respond. At six and 12 weeks, disease assessments were performed. Subsequently, disease assessments were planned for every three months in the first year and every six months for two years.

The primary endpoint of the study was EFS, defined as the time from randomization to stable disease (SD) or progressive disease (PD) at or after the 12-week assessment, or death at any time.

Week six assessments evaluated disease burden prior to tisa-cel infusion (and after bridging, if applicable) in arm A, and determined whether responses were sufficient for autoHCT or if a second PCT regimen was required in arm B.

At a median follow-up of 10 months (range = 2.9-23.2), the median EFS in both treatment arms was three months (hazard ratio [HR] = 1.07; 95% CI 0.82-1.40; p=0.69). In arm A, patients who presented with PD at their week six assessments had shorter EFS. Some patients responded to tisa-cel after SD or PD without additional treatment at the week 12 assessment, but the EFS analysis considered this an event.

 

In arm A, grade ≥3 adverse events (AEs) were reported in 84% of patients (compared with 90% in arm B). These AEs included grade ≥3 cytokine release syndrome (CRS) in 5% and grade ≥3 neurologic events in 3%. During the study period, 52 (32%) and 45 (28%) deaths occurred in arms A and B, respectively. The most common cause of death in each group was PD, followed by AEs.

Possible limitations of these findings include “design elements, such as optional PCT bridging therapy in arm A with potential delay of tisa-cel infusion until after week six assessment, allowance of a different PCT regimen to reach autoHCT in arm B after inadequate response to first PCT, and imbalances in relevant patient characteristics,” the authors wrote.

Any conflicts of interest declared by the authors can be found in the original abstract.

Reference

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. Abstract LBA-6. Presented at the 2021 ASH Annual Meeting, December 14, 2021.

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