Safety and efficacy of nivolumab in patients who failed to achieve a complete remission after <scp>CD19</scp>‐directed <scp>CAR</scp> T‐cell therapy in diffuse large B cell lymphoma

Gazeau, Nicolas; Mitra, Suman; Nudel, Morgane; Tilmont, Rémi; Chauvet, Paul; Srour, Micha; Moreau, Anne‐Sophie; Alidjinou, Enagnon Kazali; Manier, Salomon; Morschhauser, Franck; Labalette, Myriam; Yakoub‐Agha, Ibrahim; Beauvais, David

doi:10.1111/bjh.18775

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…Limited clinical data have suggested that CD19 CAR-T in combination with such immune-agents can further enhance the antitumor effect, especially for those who failed to achieve an early response. 23 The dual benefits of immuno-agents in terms of disease control in CNSLs and immunomodulatory augmentation of CAR-T function, make these agents a logical consideration for incorporation into CART-related combinatorial therapies for CNSLs. Moreover, previous studies have demonstrated synergistic antitumor effects between ibrutinib and immune checkpoint blockade.…”

Section: Discussionmentioning

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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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%

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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“…At 4.4 months follow-up, the combination had a manageable safety profile with an ORR of 90% (9/10), and 60% of cases achieved CR [75]. Two recent studies also suggested that both nivolumab and pembrolizumab had the potential therapeutic benefit of reversing CAR-T cell exhaustion in R/R DLBCL patients [76,77]. Mu et al demonstrated the combination and maintenance treatment with a PD-1 inhibitor in PD-1 positive R/R DLBCL patients who achieved CR/PR after CAR-T therapy experienced prolonged survival [78].…”

Section: Table 4 Summary Of Primary Cd19 Car-t Products In R/r Dlbclsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

The progress of novel strategies on immune-based therapy in relapsed or refractory diffuse large B-cell lymphoma

Zhang

Xu-Monette

et al. 2023

Exp Hematol Oncol

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Diffuse large B-cell lymphoma (DLBCL) can be cured with standard front-line immunochemotherapy, whereas nearly 30–40% of patients experience refractory or relapse. For several decades, the standard treatment strategy for fit relapsed/refractory (R/R) DLBCL patients has been high-dose chemotherapy followed by autologous hematopoietic stem cell transplant (auto-SCT). However, the patients who failed in salvage treatment or those ineligible for subsequent auto-SCT have dismal outcomes. Several immune-based therapies have been developed, including monoclonal antibodies, antibody–drug conjugates, bispecific T-cell engaging antibodies, chimeric antigen receptor T-cells, immune checkpoint inhibitors, and novel small molecules. Meanwhile, allogeneic SCT and radiotherapy are still necessary for disease control for fit patients with certain conditions. In this review, to expand clinical treatment options, we summarize the recent progress of immune-related therapies and prospect the future indirections in patients with R/R DLBCL.

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Axicabtagene-ciloleucel/nivolumab

2023

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Safety and efficacy of nivolumab in patients who failed to achieve a complete remission after CD19‐directed CAR T‐cell therapy in diffuse large B cell lymphoma

Cited by 6 publications

References 14 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

The progress of novel strategies on immune-based therapy in relapsed or refractory diffuse large B-cell lymphoma

Axicabtagene-ciloleucel/nivolumab

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