In China, Phase 2 Study of Relma-Cel in R/R MCL Finds Durable Responses

Relmacabtagene autoleucel (relma-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, produced responses in nearly three-fourths of patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) in a phase 2 study in China, meeting its end point and offering a potential treatment option for patients in this country, where CAR T-cell therapies approved in the United States are not available.

Relma-cel, tested in 59 patients, showed an objective response rate (ORR) of 71.19% at 3 months (95% CI, 57.92-82.24) with a complete response rate (CRR) of 59.32% (95% CI, 45.75-71.93), meeting its end point. Results for this trial (NCT04718883) were reported in Blood Advances.¹

After a median follow-up of 13.3 months (95% CI, 9.04-18.69), the median duration of response was 18.1 months, progression free survival was 15.5 months, and overall survival was 19.5 months. Best overall ORR and CRR reached 81.4% and 67.8%, respectively. The median time to first response was less than one month (0.95 months).

Already approved in China for R/R large B-cell lymphoma and follicular lymphoma, relma-cel could be the first CAR T-cell therapy to be approved for Chinese patients who are heavily pretreated for R/R MCL. There are 2 approved CAR T-cell therapies for MCL in the United States:

• Brexucabtagene autoleucel (brexu-cel, Tecartus;Kite Pharma), which yielded an ORR of 93% and a complete response rate (CRR) of 67% in the ZUMA-2 trial (NCT02601313).
• Lisocabtagene maraleucel (liso-cel, Breyanzi;Bristol Myers Squibb) reported an ORR of 83.1% and a CRR of 72.3% in the MCL cohort of the TRANSCEND NHL 001 trial (NCT02631044).

Relma-cel is an autologous CD-19-directed therapy with a 4-1BB costimulatory domain, thus employing the same CAR construct as liso-cel.² MCL, an aggressive B-cell non-Hodgkin lymphoma, has seen several recent treatment advances yet remains largely incurable, with high relapse rates following conventional treatment.³

The arrival of Bruton tyrosine kinase (BTK) inhibitors have significantly improved outcomes in R/R MCL, but patients who stop these therapies face a median OS ranging from 2.5 to 14.2 months, the authors wrote. Thus, they said, there is an unmet need for therapies offering durable responses.

The current study was conducted across 17 sites in China. Of the 70 enrolled patients who underwent leukapheresis, 59 ultimately received a single infusion of 100 × 10⁶ CAR-positive T cells after receiving standard lymphodepleting chemotherapy with fludarabine and cyclophosphamide.

To qualify for the study, patients must have been treated with at least 2 prior lines of therapy, including anti-CD20 antibodies, anthracycline- or bendamustine-containing chemotherapy, and BTK inhibitors.

This was a high-risk study population, the authors explained. The median age was 59 years, 25.4% had blastoid-type disease, 54.2% had BTK inhibitor-refractory disease, 28.8% had received five or more prior lines of therapy, and 59.3% had extranodal disease involvement.

The study authors noted that given the clinical features of the patients, the durability of response was especially strong. “These outcomes are clinically meaningful, especially because all patients had previously failed BTK inhibitor treatment and thus comprised a population characterized by poor prognosis and limited efficacy with conventional salvage therapies,” they wrote. “When compared with approved CAR T therapies for R/R MCL, our findings demonstrate parallels with the liso-cel TRANSCEND NHL 001 study, which reported a median PFS of 15.3 months and median OS of 18.2 months.”

Safety results. All 59 infused patients experienced treatment-emergent adverse events, with events of grade 3 or higher seen in 94.9% of patients. The most common grade 3 or higher toxicities were neutropenia (76.3%), leukopenia (69.5%), and lymphopenia (47.5%).

Cytokine release syndrome (CRS) occurred in 81.4% of patients, although grade 3 or higher CRS was seen only 6.8%, compared with 15% in ZUMA-2 for brexu-cel. Neurotoxicity occurred in 20.4% of patients overall, with grade 3 or higher in 6.8%, which the authors noted was lower than both the ZUMA-2 and the liso-cel TRANSCEND NHL 001 MCL cohort.

Of note, all CRS and neurotoxicity cases resolved fully, and no fatal treatment-related events were reported.

Infections were common, with grade 3 or higher infections in 33.9% of patients. Among 23 total deaths, 5 were attributable to COVID-19; the authors said the pandemic’s presence was an important confounder. A sensitivity analysis that excluded all COVID-19–related deaths suggested the median OS had not yet been reached, with the adjusted 12-month nonrelapse mortality rate reaching 6.8%.

The authors said the results are promising but that more studies of longer duration are needed. “The high durable response rates observed in our study could contribute to a potential shift in the treatment paradigm for R/R MCL in China,” they wrote. “ These results warrant further development and integration of relma-cel in R/R MCL treatment. Ongoing follow-up will assess relma-cel’s long-term efficacy and safety.”

References

1. Xie Y, Zhou KS, Li LF, Phase 2 study of relmacabtagene autoleucel (CD19 CAR-T) for relapsed/refractory mantle cell lymphoma in Chinese adults. Blood Adv. 2026;10(4):1134-1144. doi: 10.1182/bloodadvances.2024015763
2. Wang Y, Yang S, Yu Y, et al. Preliminary safety and efficacy of relmacabtagene autoleucel (relma-cel) in adults with moderately to severely active systemic lupus erythematosus: a phase I dose-escalation study. J Autoimmunity. 2025;157:103489. doi: 10.1016/j.jaut.2025.103489
3. Burkart M, Karmali R. Relapsed/refractory mantle cell lymphoma: beyond BTK inhibitors. J Pers Med. 2022;12(3):376. doi:10.3390/jpm12030376