BELINDA
Tisagenlecleucel Versus Standard of Care in Adult Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma: A Randomized, Open Label, Phase III Trial (BELINDA)
Phase 3N = 322NCT03570892
- Population
- Patients with aggressive B-cell lymphoma refractory to, or progressing within 12 months after, first-line therapy.
- Design
- International phase 3 trial: patients with aggressive lymphoma refractory to, or progressing within 12 months after, first-line therapy were randomly assigned to tisagenlecleucel with optional bridging therapy or to salvage chemotherapy followed by autologous HSCT. 322 patients underwent randomisation (ClinicalTrials.gov lists 330). Primary end point: event-free survival, defined as the time from randomisation to stable or progressive disease at or after the week 12 assessment, or death. Crossover to tisagenlecleucel was allowed if a defined event occurred at or after week 12.
- Primary endpoint
- EFS
- Arms
- Standard care (control): Salvage chemotherapy followed by autologous HSCT
- Tisagenlecleucel (experimental): Tisagenlecleucel with optional bridging therapy
- People
- Bishop MR, senior author Westin JR
EFSHR 1.07 (95% CI 0.82–1.40)Δ median EFS0 monthsΔ Response rate+3.8 points
Show the numbers
| Endpoint | Analysis | Tisagenlecleucel | Standard care | Effect |
|---|---|---|---|---|
| EFSRandomised patients (322); the abstract does not use the label ITT for this analysisTime from randomisation to stable or progressive disease at or after the week 12 assessment, or death (stated primary end point). | primaryBishop 2022 | median 3 months | median 3 months | HR 1.07 (95% CI 0.82–1.40)P=0.61Hazard ratio for event or death in the tisagenlecleucel group. 95.7% of the tisagenlecleucel group received tisagenlecleucel and 32.5% of the standard-care group received autologous HSCT. Lymphoma progression at week 6 occurred in 25.9% of the tisagenlecleucel group and 13.8% of the standard-care group. Ten patients in the tisagenlecleucel group and 13 in the standard-care group died from adverse events. |
| Response rateRandomised patients (322); the abstract does not state the denominatorProportion of patients with a response, as reported; the abstract gives no further definition. | primaryBishop 2022 | 46.3% | 42.5% | — |
| Endpoint | Analysis | Tisagenlecleucel | Standard care | Effect |
|---|---|---|---|---|
| EFSRandomised patients (322); the abstract does not use the label ITT for this analysisTime from randomisation to stable or progressive disease at or after the week 12 assessment, or death (stated primary end point). | primaryBishop 2022 | median 3 months | median 3 months | HR 1.07 (95% CI 0.82–1.40)P=0.61Hazard ratio for event or death in the tisagenlecleucel group. 95.7% of the tisagenlecleucel group received tisagenlecleucel and 32.5% of the standard-care group received autologous HSCT. Lymphoma progression at week 6 occurred in 25.9% of the tisagenlecleucel group and 13.8% of the standard-care group. Ten patients in the tisagenlecleucel group and 13 in the standard-care group died from adverse events. |
| Response rateRandomised patients (322); the abstract does not state the denominatorProportion of patients with a response, as reported; the abstract gives no further definition. | primaryBishop 2022 | 46.3% | 42.5% | — |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| EFS | 1.07 | 0.82–1.4 |
- Standard care (control)
- Tisagenlecleucel (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Standard care | Tisagenlecleucel |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 2 | 63.0% | 63.0% |
| 4 | 39.7% | 39.7% |
| 6 | 25.0% | 25.0% |
| 8 | 15.7% | 15.7% |