Over the past few decades, significant progress has been made in the treatment of hematologic malignancies. Both domestic and international guidelines have now recommended chimeric antigen receptor T-cell (CAR-T) therapy as a standard treatment for relapsed/refractory hematologic tumors. Recently, the latest 4-year follow-up data from the RELIANCE study—a pivotal Chinese registration trial for relmacabtagene autoleucel (relma-cel)—were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. This article explores the clinical value of relma-cel in treating B-cell non-Hodgkin lymphoma (B-NHL).
Long-term follow-up data from the RELIANCE study showed that relma-cel achieved a 4-year overall survival (OS) rate of 66.7% in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL), with complete response (CR) patients reaching an impressive 4-year OS rate of 82.5%, demonstrating significant long-term survival benefits.
Additionally, relma-cel has demonstrated efficacy and safety in treating relapsed/refractory follicular lymphoma (R/R FL) and relapsed/refractory mantle cell lymphoma (R/R MCL), potentially positioning it as a comprehensive solution for B-NHL disease management.
Breaking Barriers: CAR-T Cell Therapy Paves the Way Toward Curing Lymphoma
The ultimate goal of cancer treatment is to achieve a cure and prolong survival. Although diffuse large B-cell lymphoma (DLBCL) may present with extensive disease or be challenging to diagnose early, it remains potentially curable with appropriate and effective treatment. In recent years, advancements in systemic anti-cancer therapies have improved the OS of lymphoma patients. However, a subset of patients—particularly those with relapsed/refractory disease—still face challenges such as low response rates, high relapse rates, and limited long-term survival benefits.
Compared to traditional treatments, CAR-T cell therapy can achieve significantly higher response rates with a “single infusion” while maintaining durable anti-tumor activity, substantially improving long-term survival outcomes. Multiple international clinical studies have confirmed that CAR-T cell therapy may serve as a curative treatment for LBCL patients.
Trusted Efficacy: Relma-cel Empowers LBCL Patients to Embark on a Long-Term Survival Journey
The treatment of lymphoma has entered the era of cellular immunotherapy. Relma-cel, an autologous CD19-targeted CAR-T cell therapy, has demonstrated its efficacy and safety in treating R/R LBCL through the RELIANCE study.
The RELIANCE study is currently the largest completed registration trial in China evaluating CAR-T cell therapy in patients with relapsed/refractory B-NHL (R/R B-NHL), assessing the efficacy and safety of relma-cel in Chinese R/R LBCL patients. The study enrolled 59 Chinese R/R LBCL patients, with an objective response rate (ORR) of 60.3% at 3 months in the efficacy-evaluable population (n=58). Two-year follow-up results showed a best ORR of 77.6% and a CR rate (CRR) of 53.5%, with a median duration of response (DOR) of 20.5 months. At a median follow-up of 17.9 months, the median progression-free survival (PFS) was 7 months, while median OS was not reached, with 1- and 2-year OS rates of 75.0% and 69.3%, respectively. In the 100×10^6 dose group (the approved commercial dose), median PFS was 8.8 months, median OS was not reached, and both 1- and 2-year OS rates were 84.9%.
The latest 4-year follow-up data presented at the 2024 ASCO meeting revealed that, at a median follow-up of 48.1 months, 25 patients remained alive, with median OS not yet reached and a 4-year OS rate of 66.7%. When stratified by response, CR patients exhibited significantly higher 4-year OS rates (CR vs. PR vs. non-responders: 82.5% vs. 59.3% vs. 30.8%). These findings suggest that patients who achieve a response—particularly a CR—after pretreatment can derive greater survival benefits from relma-cel therapy.
Regarding safety, the incidences of grade ≥3 cytokine release syndrome (CRS) and neurotoxicity (NT) were 5.1% and 3.4%, respectively. Notably, no grade ≥3 CRS or NT events were observed in the 100×10^6 dose group.
The long-term follow-up data from the RELIANCE study demonstrate that relma-cel can provide durable survival for R/R LBCL patients, making a cure a tangible possibility—especially for those who achieve CR after initial treatment. Similar observations have been reported in the TRANSCEND and ZUMA-1 studies, where CAR-T-treated CR patients exhibited significantly better OS outcomes. This underscores that the depth of initial response to CAR-T therapy is a key determinant of durable remission, suggesting that individualized disease management based on post-CAR-T tumor response could optimize long-term outcomes and maximize patient benefits.
Furthermore, compared to other CD19-targeted CAR-T therapies in China, relma-cel demonstrates a relatively higher 4-year OS rate and lower risks of CRS and NT, which may be attributed to differences in CAR structural design.
Relma-cel features a unique CAR construct, incorporating a 4-1BB co-stimulatory domain, a CD28 transmembrane domain, and an optimized hinge length. Studies indicate that the 4-1BB domain enhances CAR-T cell persistence in vivo, enabling sustained immune surveillance against tumors. The CD28 transmembrane domain allows effective targeting of CD19-low tumor cells, while the optimized hinge increases CAR-T cell sensitivity to CD19 antigen recognition while maintaining stability, thereby enhancing tumor-killing potency. These structural features contribute to relma-cel’s direct, deep, and durable anti-tumor effects, ultimately offering the potential for a cure.
Leading the Way: Relma-cel Provides Comprehensive Care for R/R B-NHL
The proven efficacy and favorable safety profile of relma-cel in third-line R/R LBCL treatment have bolstered confidence in lymphoma cell immunotherapy. Currently, relma-cel is being explored for second-line LBCL treatment and even frontline therapy for high-risk LBCL patients, aiming to serve a broader clinical need.
Simultaneously, relma-cel has demonstrated clinical value in treating relapsed/refractory indolent lymphomas. As the only CAR-T therapy approved in China for R/R FL, it enables deep responses and long-term disease control. Following the impressive efficacy and safety data for R/R MCL presented at the 2023 ASH meeting, the Center for Drug Evaluation (CDE) has granted priority review for this indication, potentially making relma-cel the first CAR-T therapy approved for MCL in China.
With its expanding clinical indications, relma-cel is poised to benefit an increasing number of lymphoma patients, bringing hope for a cure to those in need.
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