P1, N=20, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

P1, N=15, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=24 --> 15

P1/2, N=80, Recruiting, Chongqing Precision Biotech Co., Ltd | Trial completion date: Jul 2024 --> Jul 2027 | Trial primary completion date: Dec 2023 --> Dec 2026

P1/2, N=80, Recruiting, Chongqing Precision Biotech Co., Ltd | Trial completion date: Jul 2024 --> Jul 2027 | Trial primary completion date: Dec 2023 --> Dec 2026

P3, N=100, Not yet recruiting, Cartesian Therapeutics | Trial completion date: Apr 2026 --> Sep 2027 | Trial primary completion date: Apr 2026 --> Nov 2026

We report a 63-year-old male who received ciltacabtagene autoleucel CAR T cells and the GPRC5D × CD3 bispecific talquetamab for early relapse of his multiple myeloma...These expanded clones exhibited an exhausted effector-memory T cell transcriptional signature, and the neoplasm itself was sensitive to dexamethasone treatment...Before and after CAR T whole-genome analyses implicated clonal outgrowth of a TET2-mutated precursor propelled by additional subclone-specific loss of heterozygosity and other secondary mechanisms. This case highlights the evolution of a CAR-carrying peripheral T cell lymphoma following CAR T cell and bispecific T cell engager therapy, offering critical insights into the clonal evolution from a predisposed hematopoietic precursor to a mature neoplasm.

P2, N=264, Active, not recruiting, Celgene | Recruiting --> Active, not recruiting

P=N/A, N=1500, Not yet recruiting, CARsgen Therapeutics Co., Ltd.

In the absence of direct evidence, the contribution of insertional mutagenesis to the development of T-cell lymphoma is currently unclear. (Funded by Johnson & Johnson and Legend Biotech USA; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).

P1, N=30, Recruiting, Wondercel Biotech (ShenZhen) | Initiation date: Nov 2024 --> Jul 2025

P3, N=100, Recruiting, Cartesian Therapeutics

P2, N=30, Recruiting, Janssen Research & Development, LLC | Trial completion date: Feb 2027 --> Aug 2026

P1, N=20, Recruiting, iCell Gene Therapeutics

P1/2, N=80, Recruiting, AstraZeneca | Trial completion date: Jun 2028 --> Sep 2028 | Trial primary completion date: Dec 2026 --> Apr 2027

P1, N=30, Recruiting, Arcellx, Inc. | Not yet recruiting --> Recruiting

Accordingly, the bispecific BC-7×21 TRuC-T cells showed better persistence in vivo so as to effectively suppress tumor growth in the NCG mouse xenograft model of MM.1S multiple myeloma. This study demonstrated that BC-7×21 TRuC-T cells, engineered through the optimization of the two subunits of TCR/CD3 complex and a co-expression cytokine strategy, may offer a novel and effective therapy for relapsed/refractory multiple myeloma.

P1, N=26, Terminated, CRISPR Therapeutics AG | Active, not recruiting --> Terminated; Patients to be followed up in the CRSP-ONC-LTF study

P1, N=18, Not yet recruiting, Chongbo Zhao

P1, N=24, Recruiting, Wuhan Union Hospital, China | Not yet recruiting --> Recruiting

P1, N=25, Not yet recruiting, Xuanwu Hospital, Beijing | Initiation date: Aug 2024 --> Feb 2025

P1, N=18, Active, not recruiting, Hrain Biotechnology Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

Current targets under investigation for the treatment of these conditions include CD19, CD20, and BCMA, among others. However, CAR-T therapy faces difficulties such as time-consuming cell manufacturing, complex and expensive process, and the possibility of severe adverse reactions complicating the treatment, etc. This article examines CAR-T therapy across various rheumatic autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic sclerosis (SSc), antisynthetase syndrome (ASS), and ANCA-associated vasculitis (AAV), highlighting both therapeutic advancements and ongoing challenges.

CART cell therapy has shown significant benefit in treatment of multiple myeloma. Many challenges persist. Novel strategies with structural modifications are being incorporated to overcome the limitations.

P2, N=50, Recruiting, Wake Forest University Health Sciences | Not yet recruiting --> Recruiting

P1/2, N=312, Active, not recruiting, Celgene | Trial completion date: Dec 2026 --> Jan 2025

P=N/A, N=15, Recruiting, Bristol-Myers Squibb | Trial completion date: May 2040 --> Mar 2031 | Trial primary completion date: May 2039 --> Mar 2031

Multi-target approaches, e.g. the bispecific BCMA×CD19 CAR-T product GC012F, are advancing through clinical development with encouraging safety and efficacy data. However, randomized controlled trials will be necessary to confirm the role and positioning of CD19-directed CAR-T cells within the current MM treatment landscape.

P1, N=12, Recruiting, Shanghai Cell Therapy Group Co.,Ltd

The poor correlation observed between these two measures prompted evaluation of those with discordant results, identifying that those with low sBCMA and high MTV frequently had low/absent BCMA expression on plasma cells and suboptimal response. Our findings highlight the potential utility of sBCMA and MTV to facilitate more personalized treatment strategies in the management of RRMM eligible for BCMA directed CAR-T.

RNA-sequencing analysis of tumour-exposed Blimp-1 KO CAR-T cells confirmed the presence of a memory-like transcriptomic signature and additionally, revealed enhanced ribosome biogenesis, and repressed CAR-T cell dysfunction as mechanisms that could be contributing to improved anti-tumour activity. Put together, our findings show that dampening Blimp-1 expression altered the phenotype and function of anti-BCMA CAR-T cells, leading to augmented therapeutic efficacy in MM.

P1, N=12, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

P1, N=9, Recruiting, Wuhan Union Hospital, China | Not yet recruiting --> Recruiting

The present study demonstrated a low toxicity of BCMA CAR T-cell injection, with manageable side effects and good anticancer activity and without observable adverse effects. This study provides data to support future clinical studies of BCMA CAR T-cell injection for MM.

P1, N=38, Not yet recruiting, Carbiogene Therapeutics Co. Ltd.

P=N/A, N=15, Recruiting, Bristol-Myers Squibb

We optimized different dual-targeting approaches, including co-transduction of two lentiviral vectors, bicistronic, tandem, loop and pool strategies, based on our academic anti-CD19 (ARI0001) and anti-BCMA (ARI0002h) CAR-T cells. ARI0003 CAR-T cells were effectively manufactured under Good Manufacturing Practice conditions, with reduced risk of genotoxicity compared to other dual-targeting approaches. A first-in-human phase I clinical trial (CARTD-BG-01, NCT06097455) has been initiated to evaluate the safety and efficacy of ARI0003 in NHL.

P1/2, N=49, Recruiting, Omar Nadeem, MD | Not yet recruiting --> Recruiting

In this exciting and rapidly evolving treatment landscape, this review evaluates the most recent clinical and preclinical data pertaining to these new cellular immunotherapies and explores strategies to overcome resistance pathways. On the protracted journey to a long-term cure, we outline the challenges that lie ahead and ask, 'Are we there yet?'

P1, N=50, Not yet recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

P1, N=24, Not yet recruiting, Wuhan Union Hospital, China

P1, N=50, Not yet recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

P2, N=146, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2025 --> Feb 2025 | Trial primary completion date: Dec 2025 --> Feb 2025