CD19-directed CAR-T therapy Carteyva (relmacabtagene autoleucel, relma-cel) has already been approved in China for relapsed/refractory large B-cell lymphoma and follicular lymphoma. But how effective and safe is it for patients with relapsed or refractory mantle cell lymphoma (R/R MCL), particularly those who have failed multiple lines of therapy including BTK inhibitors?
A pivotal, multicenter Phase II study conducted across 17 leading centers in China—led by Peking University Cancer Hospital—now provides high-level clinical evidence that relma-cel may represent a promising new treatment option for this high-risk population.
MCL: A High-Risk Disease with Limited Options After BTK Inhibitor Failure
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma characterized by the t(11;14) translocation and cyclin D1 overexpression. Although BTK inhibitors have improved outcomes, patients who relapse or are refractory after BTK inhibitor therapy face a dismal prognosis, with median overall survival ranging from 2.5 to 14.2 months.
Globally, CD19 CAR-T therapies such as Brexucabtagene autoleucel and Lisocabtagene maraleucel have been approved in the United States for R/R MCL. However, these products are not approved in China, and clinical data in China remain limited.
As a domestically developed CD19-targeted CAR-T therapy incorporating a 4-1BB co-stimulatory domain, relma-cel has demonstrated strong efficacy and manageable safety in B-cell lymphomas. Its role in Chinese R/R MCL patients—especially those failing BTK inhibitors—has now been specifically evaluated in this key Phase II study.
Study Design: Focused on Heavily Pretreated Chinese R/R MCL Patients
This open-label, single-arm, multicenter Phase II trial enrolled adults (≥18 years) with pathologically confirmed R/R MCL who had received at least two prior lines of therapy, including:
- Anti-CD20 monoclonal antibody
- Anthracycline- or bendamustine-containing chemotherapy
- A BTK inhibitor
A total of 96 patients were screened, and 59 received a single infusion of relma-cel (1×10⁸ CAR-positive T cells) and comprised the primary analysis population.
The cohort represented a high-risk group:
- Median age: 59 years (32.2% ≥65 years)
- 79.7% male
- 28.8% had ≥5 prior lines of therapy
- 54.2% were primary refractory to BTK inhibitors
- 59.3% had extranodal involvement
- 16.9% had high-risk MIPI scores
The primary endpoint was 3-month objective response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
Strong Efficacy: High Response Rates and Durable Disease Control
After a median follow-up of 13.3 months:
- 3-month ORR: 71.19%
- 3-month CR rate: 59.32%
- Best ORR: 81.36%
- Best CR rate: 67.80%
- Median time to first response: 0.95 months
Importantly, responses were consistent across most predefined subgroups, including:
- BTK inhibitor–refractory patients (CRR 65.6%)
- Patients <65 years (CRR 65.0%)
- Patients with bone marrow involvement (CRR 77.3%)
Durability outcomes were encouraging:
- Median DOR: 18.1 months
- Median PFS: 15.5 months
- Median OS: 19.5 months
- 12-month OS rate: 68.9%
Sensitivity analysis excluding COVID-related deaths showed median OS was not reached, suggesting potential long-term survival benefit.
These results are comparable to internationally approved CAR-T therapies, despite a high proportion of high-risk features in this Chinese cohort.
Manageable Safety Profile
All patients experienced treatment-emergent adverse events, primarily hematologic toxicities such as neutropenia and leukopenia—consistent with other CD19 CAR-T products.
CAR-T–associated toxicities were manageable:
- Any-grade CRS: 81.4%
- Grade ≥3 CRS: 6.8%
- Any-grade neurotoxicity (NT): 13.6%
- Grade ≥3 NT: 6.8%
All severe CRS and NT events fully resolved. No treatment-related deaths occurred.
The 12-month non-relapse mortality (NRM) rate was 14.5%, but only 6.8% after excluding COVID-related deaths.
CAR-T expansion kinetics correlated with treatment response, suggesting potential predictive biomarkers for future precision therapy.
Conclusion
This multicenter Phase II trial is the first high-level clinical evidence confirming that relma-cel provides:
- High response rates
- Durable remission
- Manageable safety
in heavily pretreated Chinese patients with R/R MCL, including those who failed BTK inhibitors.
As China’s domestically approved CD19 CAR-T therapy, relma-cel may reshape the treatment landscape for R/R MCL in China and provide new hope for patients with limited options.
Further randomized studies, larger cohorts, and long-term follow-up are warranted to confirm long-term efficacy and explore combination strategies with BTK inhibitors or bispecific antibodies.
Reference: Xie Y, et al. Blood Advances. 2026 Feb 24;10(4):1134–1144.
