Relapsed/refractory (R/R) central nervous system lymphoma (CNSL) has a dismal prognosis, with a median overall survival (OS) of just 4 months. While CAR-T cell therapy has revolutionized R/R large B-cell lymphoma (LBCL) treatment, data on its use in CNSL—particularly in Asian populations—remain limited.
Relmacabtagene autoleucel (relma-cel), a CD19-directed CAR-T therapy, has shown promising results in the pivotal RELIANCE trial, leading to its approval in China for R/R LBCL. However, real-world evidence in CNSL was lacking. To address this, Professor Jian-Qing Mi’s team at Ruijin Hospital conducted the first and largest multicenter retrospective study on relma-cel for R/R CNSL, published in the Journal for ImmunoTherapy of Cancer.
Study Design & Patient Characteristics
The study analyzed 22 R/R CNSL patients (12 primary, 10 secondary) treated with relma-cel across 12 Chinese centers (2021–2023). Key baseline features:
- Median age: 56 years (45.5% >60)
- High-risk factors: 23.1% had double/triple-hit lymphoma (DHL/THL)
- Median prior therapies: 2 (range: 1–5)
- 36.4% received relma-cel as consolidation (despite prior CR/PR, deemed high-risk)
Key Efficacy Findings
- Best ORR: 90.9%
- Best CR rate: 68.2%
- CNS responses: 100% (72.7% achieved CNS CR)
- Durability:
- 81.3% of responders remained in remission at median follow-up (316 days)
- 50% maintained CNS response >1 year
- Survival:
- 1-year PFS: 64.4%
- 1-year OS: 79.2%
Prognostic Factors
- Pre-infusion CR/PR patients had 100% 1-year PFS vs. 41.7% in R/R patients (P=0.02).
- Failure to achieve CR by 3 months predicted poorer outcomes (1-year PFS: 83.3% vs. 37%, P=0.03).
- ASCT + CAR-T showed no significant benefit over CAR-T alone.
Safety Profile
- CRS: 72.7% (93.7% Grade 1–2; no Grade 4–5)
- ICANS: 36.4% (only 1 Grade 3 case)
- No CAR-T-related deaths
- Infections: 8 cases (including 3 severe COVID-19, 2 fatal)
CAR-T Expansion & Biomarkers
- Robust peripheral blood expansion (peak at 1.43 weeks).
- CSF penetration confirmed in all 8 tested patients.
- Higher CAR-T peak levels correlated with neurotoxicity (P=0.01).
- CRS severity linked to elevated IL-6, IFN-γ, and sIL-2R.
Combination Strategies
- BTKi/PD-1 inhibitors triggered CAR-T re-expansion, with 4 patients maintaining remission for 15.5 months on dual immunotherapy.
- Low CSF CAR-T levels did not preclude sustained responses, suggesting immune memory effects.
Conclusions & Future Directions
This study confirms:
- Relma-cel is effective and safe in R/R CNSL, even in high-risk patients.
- Early CAR-T consolidation may benefit salvage-sensitive cases.
- PD-1i/BTKi combinations could enhance CAR-T persistence.
Next steps:
- Larger prospective trials to compare CAR-T vs. ASCT.
- Optimize timing and combinations for durable CNS control.
This real-world evidence supports relma-cel as a transformative option for R/R CNSL, with potential for further refinement in future studies.Journal Reference: Journal for ImmunoTherapy of Cancer [2023].
Clinical Implications: Early CAR-T use and combo strategies may improve outcomes in this aggressive disease.
Journal Reference
Yu W, Huang L, Mei H, et al. Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China.Journal for ImmunoTherapy of Cancer 2024;12:e008553.doi:10.1136/jitc-2023-008553
