Long-term outcomes of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma: Updated results of the RELIANCE study

Ying, Zhitao; Yang, Haiyan; Guo, Ye; Li, Wenyu; Zou, Dehui; Zhou, Daobin; Zhao, Wei‐Li; Zhang, Mingzhi; Wu, Jianqiu; Liu, Hui; Wang, Chris; Ma, Laura; Su, Yang; Zhou, Zhiqing; Qin, Yun; Song, Yuqin; Zhu, Jun

doi:10.1016/j.jcyt.2022.10.011

Cited by 5 publications

(3 citation statements)

References 21 publications

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“…The median duration of NT was also shorter in our study (5 vs 15 days, respectively). 10 In addition to variations in CAR-T products, it might be partly due to evolving practices of toxicity management, including the early and increased use of tocilizumab, corticosteroids, and supportive cares in real-world settings.…”

Section: Discussionmentioning

confidence: 99%

“…It expresses the same CAR as lisocabtagene maraleucel with a 4-1BB costimulatory domain. In the registration RELIANCE trial (NCT04089215), 10 relma-cel demonstrated high rates of durable disease responses and a manageable safety profile. Based on these results, relma-cel has been approved by the Chinese National Medical Products Administration and commercialized in China for the treatment of R/R LBCL patients.…”

Section: Introductionmentioning

confidence: 99%

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Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China

Yu,

Huang,

Mei

et al. 2024

J Immunother Cancer

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BackgroundRelapsed/refractory (R/R) central nervous system lymphomas (CNSLs) are associated with a poor prognosis. Relmacabtagene autoleucel (relma-cel), expressing the same chimeric antigen receptor (CAR) as lisocabtagene maraleucel, with an optimized commercial-ready process developed in China, demonstrated remarkable efficacy and manageable safety in the pivotal RELIANCE study. However, no published data are available on the “real-world” use of relma-cel, especially for patients with CNS involvement.Patients and methodsRetrospective analyses were conducted for commercial relma-cel used in patients with R/R CNSL at 12 clinics. The primary endpoint was to evaluate the proportion of patients who achieved complete response (CR) at 3 months. Secondary endpoints included best complete response (BCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and the incidence of adverse events.ResultsAmong the 22 CNSL patients (12 primary CNSLs; 10 secondary CNSLs), the best overall response rate was 90.9% and the BCR rate was 68.2%. With median follow-up of 316 days (range, 55–618 days), the estimated 1-year PFS rate, DOR, and OS rate were 64.4%, 71.5%, and 79.2%, respectively. Significant clinical benefits were observed in patients who were in durable CR or partial response to the most recent prior therapy preleukapheresis and received relma-cel as consolidation therapy (n=8), with 1-year PFS rate of 100.0% versus 41.7% (p=0.02). In addition, in terms of primary endpoint, non-CR at 3 months postinfusion seemed to be predictive of a worse prognosis, with an estimated 1-year PFS of 83.3% versus 37.0% (p=0.03), respectively. CRS occurred in 72.9% of patients (grade 3: 4.5%) and immune effector cell-associated neurotoxicity syndrome in 36.4% of patients (grade 3: 4.5%). With the add-on agent PD-1 inhibitor (tislelizumab) to the ongoing BTKi, significant re-expansions of CAR T-cell were detected by quantitative PCR or flow cytometry after a median of 2 weeks (range, 12–32 days).ConclusionsThis study was the first and largest real-world study of commercial relma-cel for R/R CNSL, demonstrating promising efficacy and acceptable safety. We reaffirmed the benefit of immuno-agents such as BTKi or PD-1 inhibitor on CAR T-cell re-expansion and hypothesized a dual-agent CAR-T related combinatorial therapies, which warrants further validation. Most importantly, we highlighted the earlier use of CAR T-cell therapy as a consolidative therapy for patients sensitive to salvage therapy, which provided an impetus and inspired-future strategy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China

Yu,

Huang,

Mei

et al. 2024

J Immunother Cancer

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“…Chimeric antigen receptor T-cell (CAR-T) therapy is an innovative immunotherapeutic approach that genetically modifies T cells to express specific antigen receptors, enabling them to recognize antigens present on the surface of tumor cells. This therapy has demonstrated remarkable efficacy in treating relapsed/refractory acute lymphoblastic leukemia (ALL), [1][2][3] chronic lymphoblastic leukemia (CLL), non-Hodgkin's lymphoma (NHL), [4][5][6] and multiple myeloma (MM). [7][8][9][10] Notably, CD19 CAR-T cells have achieved complete remission (CR) rates ranging from 62% to 86% in B-cell ALL (B-ALL) patients who are negative for micro-residual disease (MRD).…”

Section: Introductionmentioning

confidence: 99%

Advances in research on factors affecting chimeric antigen receptor T‐cell efficacy

Zhou,

Zhu,

Xiao

2024

Cancer Medicine

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Chimeric antigen receptor T‐cell (CAR‐T) therapy is becoming an effective technique for the treatment of patients with relapsed/refractory hematologic malignancies. After analyzing patients with tumor progression and sustained remission after CAR‐T cell therapy, many factors were found to be associated with the efficacy of CAR‐T therapy. This paper reviews the factors affecting the effect of CAR‐T such as tumor characteristics, tumor microenvironment and immune function of patients, CAR‐T cell structure, construction method and in vivo expansion values, lymphodepletion chemotherapy, and previous treatment, and provides a preliminary outlook on the corresponding therapeutic strategies.

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Nanomaterials Boost CAR‐T Therapy for Solid Tumors

Long,

Wang,

Jiang

et al. 2024

Adv Healthcare Materials

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T cell engineering, particularly via chimeric antigen receptor (CAR) modifications for enhancing tumor specificity, has shown efficacy in treating hematologic malignancies. The extension of CAR‐T cell therapy to solid tumors, however, is impeded by several challenges: the absence of tumor‐specific antigens, antigen heterogeneity, a complex immunosuppressive tumor microenvironment, and physical barriers to cell infiltration. Additionally, limitations in CAR‐T cell manufacturing capacity and the high costs associated with these therapies restrict their widespread application. The integration of nanomaterials into CAR‐T cell production and application offers a promising avenue to mitigate these challenges. Utilizing nanomaterials in the production of CAR‐T cells could decrease product variability and lower production expenses, positively impacting the targeting and persistence of CAR‐T cells in treatment and minimizing adverse effects. This review comprehensively evaluates the use of various nanomaterials in the production of CAR‐T cells, genetic modification, and in vivo delivery. It discusses their underlying mechanisms and potential for clinical application, with a focus on improving specificity and safety in CAR‐T cell therapy.This article is protected by copyright. All rights reserved

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Long-term outcomes of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma: Updated results of the RELIANCE study

Cited by 5 publications

References 21 publications

Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China

Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China

Advances in research on factors affecting chimeric antigen receptor T‐cell efficacy

Nanomaterials Boost CAR‐T Therapy for Solid Tumors

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