At first evaluation (month 1) following brexu-cel infusion, the best overall response rate was 82% among patients who eventually relapsed (n = 61), including 28 complete responses (CRs; 46%) and 22 partial responses (PRs; 36%). Nine patients (14.6%) exhibited primary refractory disease, including 1 patient who died due to disease progression, and 2 patients (3.3%) were unevaluable. The median time to progression was 4.5 months. Progression occurred within the first 3 months of infusion in 17 patients (28%), between 3 and 6 months after infusion in 25 patients (42%), and more than 6 months after infusion in 18 patients (30%).
After a median follow-up of 15 months post–CAR T-cell therapy progression, the median overall survival following progression (OS2) was 5.8 months (95% CI, 3.2-11.3), with estimated 6- and 12-month OS2 rates of 48.4% (95% CI, 34.5%-60.9%) and 29.8% (95% CI, 17.5%-43.2%), respectively. Survival outcomes were significantly associated with the timing of relapse; patients who progressed within 3 months of infusion had a median OS2 of 1.8 months (95% CI, 1.1-5.8) compared with 6.7 months (95% CI, 3.4-not available [NA]) among those who relapsed between 3 to 6 months or more than 6 months following infusion and 9.0 months (95% CI, 3.3-NA) among those who relapsed more than 9 months after infusion (P = .0137).
Patients with a history of early progression after first-line therapy (POD24; n = 51/60; 85%) also exhibited inferior outcomes, with a median OS2 of 4.7 months (95% CI, 2.0-9.0), compared with patients with later progression (n = 9/60; 15%), whose median OS2 was not reached (95% CI, 3.4 months-NA; estimated 1-year OS2 rate, 60%; 95% CI, 19.5%-85.2%; P = .0704). Among 39 total deaths, lymphoma progression accounted for the majority (n = 35; 90%), whereas infections represented the remaining causes (n = 4).
“Patients with MCL in the DESCAR-T registry who experienced [progression] after brexu-cel injection had poor outcomes, with no standardized treatment currently available for this challenging[-to-treat] population,” lead study author Marion Aymard, MD, of the Department of Hematology at Institut Curie in Saint-Cloud, France, and colleagues noted in a paper published in Blood Advances. “Despite the small sample size, our findings suggest that T-cell engagers may provide durable responses, [whereas] no benefit seems to be observed with targeted therapies [like BTK inhibitors and anti–BCL-2 therapies].”
What Was the Design of This MCL Analysis of the DESCAR-T Study?
Data for this analysis were derived from the DESCAR-T registry, a comprehensive national French database that collected clinical information from patients with hematologic malignancies who were eligible for or treated with commercial CAR T-cell therapies.1,2 All patients included in the registry were discussed and approved for treatment by a multidisciplinary tumor board at an accredited CAR T-cell center, and informed consent for noninterventional data use was obtained prior to inclusion.
Between 2019 and 2024, 217 patients with relapsed or refractory MCL were enrolled in the registry with intent to receive brexu-cel.1 Of these patients, 186 (86%) ultimately underwent CAR T-cell infusion, and 178 were evaluable for response after exclusion of 8 with incomplete data. The present analysis included patients who experienced disease progression, relapse, or refractory disease following brexu-cel treatment. Disease progression and response were assessed by the treating hematologists according to local practice standards.
The study’s primary end points were OS2, defined as the time from documented CAR T-cell therapy progression to death from any cause, and progression-free survival post-progression (PFS2), defined as the time from brexu-cel progression to progression after salvage therapy. Secondary end points included characterization of baseline patient and disease features, detailed assessment of treatment strategies used after CAR T-cell therapy progression, response rates and outcomes according to specific salvage regimens, and the identification of prognostic factors associated with survival outcomes following CAR T-cell therapy relapse.
What Were the Baseline Characteristics of the Patients Evaluated in the MCL Analysis?
Among the 61 patients included in this analysis, 54 (88.5%) were male, and the median age at the time of the CAR T-cell medical tumor board assessment was 66 years (range, 39-83).
Disease risk was high across several prognostic categories. Of the 53 patients with available data, 19 (36%) exhibited a high MCL International Prognostic Index (MIPI) score. Ki-67 score was elevated in most cases, with 32 of 42 patients (76%) demonstrating Ki-67 expression levels greater than 30%. TP53 mutational status was available for 43 patients, and 13 patients (30%) were found to harbor TP53 mutations. A blastoid variant was reported in 18 of 57 evaluable patients (31.6%).
Before receiving brexu-cel, patients had received a median of 3 prior lines of therapy (range, 2-8). All patients had received prior immunochemotherapy with rituximab (Rituxan), and nearly all patients (97%; n = 59) had previously been treated with a BTK inhibitor. Additionally, 44% of patients (n = 27) had undergone stem cell transplantation, including autologous transplantation in 25 patients and allogeneic transplantation in 2 patients. In total, 63.8% of evaluable patients (n = 37/58) were refractory to their most recent line of treatment.
Ninety-two percent of patients had received bridging therapy, predominantly immunochemotherapy or chemotherapy. At the time of brexu-cel infusion, 36% of patients were in response to this bridging therapy, including 3 patients with CR and 17 patients with PR; all other patients were in progressive disease at the time of infusion.
What Were the Salvage Therapy Outcomes in the MCL Population?
Among 49 patients who received salvage therapy, 33% received lenalidomide with or without rituximab, 27% received chemotherapy or immunochemotherapy, 16% received a BTK inhibitor or venetoclax, 14% received a T-cell engager (all glofitamab-gxbm [Columvi]), 6% received other targeted therapy, and 4% underwent radiation. In the salvage therapy population, the response rate was 20.4%, including 9 CRs and 1 PR.
The respective overall response/CR rates according to type of salvage therapy were as follows:
- Lenalidomide-based therapy: 18.8%/18.8%
- Chemotherapy or immunochemotherapy: 23%/15%
- T-cell engager: 43%/43%
- Radiation: 50%; 50%
- BTK inhibitor: 0%/0%
- Other targeted therapies: 0%/0%
At a median follow-up of 15 months post-salvage therapy, the median PFS2 was 1.8 months (95% CI, 1.4-2.7), and the estimated 6- and 12-month PFS2 rates were 24.6% (95% CI, 13.2%-37.7%) and 19.7% (95% CI, 9.5%-32.4%), respectively.
The 1-year PFS2 rates according to type of salvage therapy were:
- Lenalidomide-based therapy: 15.6% (95% CI, 2.5%-39.1%)
- Chemotherapy or immunochemotherapy: 23.1% (95% CI, 5.6%-47.5%)
- T-cell engager: 42.9% (95% CI, 9.8%-73.4%)
- Radiation: 50% (95% CI, 0.6%-91%)
Among patients who received a T-cell engager, the 1-year response rate was 100%. Notably, none of these patients had a blastoid variant or a high Ki-67 score. Two of these patients each had a high MIPI score and a history of POD24 disease.
The estimated 1-year OS2 rates according to type of salvage therapy were:
- Lenalidomide-based therapy: 36% (95% CI, 10.8%-62.8%)
- Chemotherapy or immunochemotherapy: 36% (95% CI, 11.7%-61.3%)
- T-cell engager: 57.1% (95% CI, 17.2%-83.7%)
- Radiation: 0%
- BTK inhibitor/venetoclax: 0%
- Other targeted therapies: 0%
References
- Aymard M, Morgane Cheminant, Roch Houot, et al. Outcome of patients with mantle cell lymphoma after failure of anti-CD19 CAR-T cell therapy: a DESCAR-T study by Lysa Group. Blood Advances. Published online September 30, 2025. doi:10.1182/bloodadvances.2025017234
- French register of patients with hemopathy eligible for CAR-T cell treatment (DESCAR-T). ClinicalTrials.gov Updated January 27, 2025. Accessed October 7, 2025. https://www.clinicaltrials.gov/study/NCT04328298
