Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.

Prior therapy-mediated loss of plasma cell BCMA expression before teclistamab treatment, measured by immunohistochemistry, was observed in 3 patients, none of whom responded to teclistamab, and one of whom also did not respond to ciltacabtagene autoleucel. Whole exome sequencing of tumor DNA from one patient revealed biallelic loss of TNFRSF17 following treatment with belantamab mafodotin. Low-to-undetectable peripheral blood soluble BCMA levels correlated with the absence of BCMA expression by bone marrow plasma cells. Thus, although rare, loss of BCMA expression following TNFRSF17 gene deletions can occur following any BCMA-directed therapy and prevents response to subsequent anti-BCMA-directed treatments, underscoring the importance of verifying the presence of a target antigen.

In summary, preexisting cytopenias and hyperferritinaemia indicated long duration of grade ≥3 post-CAR T-cell cytopenias. Prolonged cytopenia may be related to immune remodelling with a shift in the CAR-negative T-cell subsets following CAR T-cell therapy.

P1, N=36, Recruiting, Tongji Hospital | N=18 --> 36 | Trial completion date: May 2024 --> May 2027 | Trial primary completion date: Feb 2024 --> Feb 2027

P3, N=618, Recruiting, Celgene

P1, N=0, Withdrawn, Jonsson Comprehensive Cancer Center | N=30 --> 0 | Not yet recruiting --> Withdrawn

This study highlights the superior efficacy of anti-BCMA-CAR3 T cells against both low and high BCMA-expressing MM cells, surpassing anti-BCMA-CAR2 T cells. These findings suggest potential for advancing anti-BCMA-CAR3 T cells in chimeric antigen receptor T (CAR-T) therapy for relapsed/refractory MM.

These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma.

P2, N=78, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Initiation date: Apr 2024 --> Dec 2024

In conclusion, this study showcases the need to study the influence of different CAR architectures based on an identical scFv individually. It indicates that current scFv-based anti-BCMA CAR with clinical utility may already be at their functional optimum regarding the known structural variations of the scFv linker.

We identified potential immunotherapy targets on CAR T cells, like PD1, to improve their functionality and durability. Our work provides evidence that an immunosuppressive microenvironment causes resistance to CAR T cell therapies in multiple myeloma.

P1, N=40, Not yet recruiting, Nexcella Inc. | Phase classification: P1b --> P1 | Initiation date: Jan 2024 --> May 2024 | Trial primary completion date: Dec 2025 --> Dec 2026

P=N/A, N=260, Not yet recruiting, Peking University People's Hospital

Overall, this study highlights the potential beneficial effect of a higher BMI on CAR-T cell therapy outcomes.

P2, N=32, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting

Our study demonstrates a design concept of CAR-T cells independent of antigen specificity and provides an alternative approach for improving the efficacy of CAR-T cell therapy.

P1, N=10, Not yet recruiting, Wuhan Union Hospital, China

P=N/A, N=50, Recruiting, Bristol-Myers Squibb

Dual-antigen targeting augmented CAR T-cell secretion of engineered IL-18 and facilitated elimination of larger myeloma burdens in vivo. Our results demonstrate that combination of engineered IL-18 secretion and multi-antigen targeting can eliminate myeloma with weak antigen expression through distinct mechanisms.

P1/2, N=126, Completed, Janssen Research & Development, LLC | Phase classification: P1b --> P1/2

Finally, we demonstrate that non-classical monocytes are enriched in the myeloma niche and may induce CAR-T cell dysfunction through mechanisms that include TGFβ. These findings shed new light on the role of cytotoxic CD4+ T cells in disease progression after CAR-T cell therapy.

P1, N=30, Recruiting, RenJi Hospital | Not yet recruiting --> Recruiting

P1/2, N=121, Active, not recruiting, CARsgen Therapeutics Co., Ltd. | Recruiting --> Active, not recruiting

P2, N=136, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting

Based on the cocultures, adding pomalidomide significantly promoted IFN-γ and TNF-α secretion (P < .05). Based on the above clinical and in vitro studies demonstrating the co-administration of pomalidomide with CAR-T cell treatment demonstrated favorable tolerability and therapeutic effectiveness in RRMM or B-cell leukemia/lymphoma.

P1, N=20, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P1/2, N=120, Recruiting, CARsgen Therapeutics Co., Ltd. | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=24, Recruiting, Nanjing University School of Medicine

P2, N=30, Recruiting, Cartesian Therapeutics | Not yet recruiting --> Recruiting

Alternative immune cells, including natural killer T cells and invariant natural killer T cells, exhibit innate anti-tumor activity and reduced toxicity. This review summarizes several recent clinical trial reports and preclinical studies from the 2023 American Society of Hematology (ASH) annual meeting on dual-targeted CAR T-cell immunotherapy for hematological malignancies.

P=N/A, N=24, Recruiting, Lingli Dong

P1, N=15, Active, not recruiting, Shanghai Simnova Biotechnology Co.,Ltd. | Recruiting --> Active, not recruiting | Trial completion date: May 2023 --> Dec 2024

P2, N=30, Not yet recruiting, Cartesian Therapeutics | Initiation date: Nov 2023 --> Feb 2024

P1, N=16, Recruiting, Technische Universität Dresden | Not yet recruiting --> Recruiting

Bispecific antibodies offer superior efficacy and tolerability compared to ADCs, but prolonged exposure causes significant cumulative infectious risk. In this review, we will examine the role of BCMA in MM biology, the approved and emerging therapies targeting this antigen, and how these agents can be optimally sequenced.

P2, N=264, Recruiting, Celgene | Trial primary completion date: Dec 2023 --> Jul 2025

P1, N=15, Recruiting, City of Hope Medical Center | Initiation date: Dec 2023 --> Mar 2024

P2, N=30, Recruiting, Cartesian Therapeutics | Trial completion date: Dec 2023 --> Mar 2026 | Trial primary completion date: Dec 2023 --> Mar 2025

P1, N=231, Recruiting, Poseida Therapeutics, Inc. | N=135 --> 231 | Trial completion date: Mar 2040 --> Dec 2039 | Trial primary completion date: Jun 2025 --> Dec 2027

P1, N=18, Recruiting, Shanghai Changzheng Hospital | Not yet recruiting --> Recruiting

CB-011 cells were protected from natural killer (NK) cell-mediated cytotoxicity in vitro and in vivo due to endogenous promoter-driven expression of B2M-HLA-E. Potent antitumor efficacy, when combined with an immune-cloaking armoring strategy to dampen allograft rejection, offers optimized therapeutic potential in multiple myeloma.

P1, N=30, Not yet recruiting, RenJi Hospital