Chimeric antigen receptor T-cell therapy for multiple myeloma

Hosen, Naoki

doi:10.1007/s12185-020-02827-8

Cited by 9 publications

(5 citation statements)

References 21 publications

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“…Multiple myeloma (MM) is a hematological malignancy caused by the malignant proliferation of plasma cells in the bone marrow ( 1 ). It is now clinically treated with chemotherapy, autologous hematopoietic stem cell transplantation (Auto-HSCT), proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, but it will eventually relapse.…”

Section: Introductionmentioning

confidence: 99%

Prolonged hematological toxicity in patients receiving BCMA/CD19 CAR-T-cell therapy for relapsed or refractory multiple myeloma

Zhao

Sun

et al. 2022

Front. Immunol.

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Although chimeric antigen receptor T (CAR-T) cell therapy has been indicated to be effective in treating relapsed or refractory multiple myeloma (R/R MM), severe hematological toxicity (HT) remains an intractable issue. This study enrolled 54 patients with R/R MM following combined infusion of anti-CD19 and anti-BCMA CAR-T cells. The results showed that the rates of severe cytopenia were high, including severe neutropenia (28/54, 52%), severe anemia (15/54, 28%), and severe thrombocytopenia (18/54, 33%). Moreover, the incidence of prolonged HT (PHT) on Day 28 post-infusion was 52% (28/54), including 46% for severe neutropenia, 30% for severe anemia, and 31% for severe thrombocytopenia. Patients with PHT had a poorer median progression-free survival (PFS) and overall survival (OS) than patients without PHT (P=0.011; P=0.007). Furthermore, Cox regression analyses showed that PHT was an independent risk factor for PFS and OS. Univariate analyses showed that IFNγ (OR: 1.046; 95% CI: 1.002-1.093, P=0.042) and severe HT after lymphodepletion chemotherapy (OR: 0.082; 95% CI: 0.017-0.404; P=0.002) were independent risk factors for PHT. In conclusion, these results indicated that PHT was associated with poor outcomes following CAR-T-cell therapy in MM patients. Early detection and management of PHT would be beneficial for the prevention of life-threatening complications and improvement in the survival of patients after CAR-T-cell therapy.Clinical trial registrationThis trial was registered on 1 May 2017 at http://www.chictr.org.cn as ChiCTR-OIC-17011272.

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Section: Introductionmentioning

confidence: 99%

Prolonged hematological toxicity in patients receiving BCMA/CD19 CAR-T-cell therapy for relapsed or refractory multiple myeloma

Zhao

Sun

et al. 2022

Front. Immunol.

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“…However, a trial (NCT02135406) of tisagenlecleucel combined with ASCT produced only a poor clinical benefit in ten MM subjects [123]. Meanwhile, emphasis has shifted to BCMA as a major focus of myeloma-based studies applying the principles of CAR T-cell technology [124,125]. Several of these products, based on the BCMA target, are described below.…”

Section: Autologous Car T-cell Therapymentioning

confidence: 99%

B-Cell Maturation Antigen (BCMA) As a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma

Abramson¹

2020

Preprint

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During the past two decades there has been a major shift in the choice of agents to treat multiple myeloma, whether newly diagnosed or in the relapsed/refractory stage. The introduction of new drug classes, such as proteasome inhibitors, immunomodulators, and anti-CD38 and anti-SLAMF7 monoclonal antibodies, coupled with autologous stem cell transplantation, have approximately doubled the disease’s five-year survival rate. However, this positive news is tempered by the realization that these measures are not curative and patients eventually relapse and/or become resistant to the drug’s effects. Thus, there is a need to discover newer myeloma-driving molecular markers and develop innovative drugs designed to precisely regulate the actions of such putative targets. B cell maturation antigen (BCMA), which is found almost exclusively on the surfaces of malignant plasma cells to the exclusion of other cell types, including their normal counterparts, has emerged as a specific target of interest in this regard. Immunotherapeutic agents have been at the forefront of research designed to block BCMA activity. These agents encompass monoclonal antibodies, such as the drug conjugate belantamab mafodotin; bispecific T-cell engager strategies exemplified by AMG 420; and chimeric antigen receptor (CAR) T-cell therapeutics that include idecabtagene vicleucel (bb2121) and JNJ-68284528.

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“…MM is characterized by the presence of clonal plasma cells that accumulate within the bone marrow, disrupting the normal hematopoiesis, and it is further distinguished by the abnormal production of immunoglobulins, which can be detected in both serum and urine [5,6]. Upon diagnosis of MM, patients often present persistent and nonspecific symptoms, which may delay the diagnosis and early treatment initiation.…”

Section: Introductionmentioning

confidence: 99%

“…BCMA, a member of the tumor necrosis factor receptor superfamily 17 (TNFRSF17) and a transmembrane glycoprotein, stands as the key surface antigen target for CAR-T cell therapy for the treatment of multiple myeloma. BCMA exhibits selective expression in malignant plasma cells, with lower levels in normal plasma cells, and it is notably absent in non-hematological tissues [6,10,19]. However, due to the fluctuating levels of BCMA expression in malignant plasma cells, BCMA downregulation, and the heterogeneous nature of tumor antigens in MM, researchers are investigating additional target antigens, including CD19, SLAMF7, GPRC5D, CD138, CD38, CD70, NKG2DL, and kappa/lambda light chains [10].…”

Section: Introductionmentioning

confidence: 99%

An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis

Pereira,

Bergantim

2024

IJMS

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Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy’s efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.

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Chimeric antigen receptor T-cell therapy for multiple myeloma

Cited by 9 publications

References 21 publications

Prolonged hematological toxicity in patients receiving BCMA/CD19 CAR-T-cell therapy for relapsed or refractory multiple myeloma

Prolonged hematological toxicity in patients receiving BCMA/CD19 CAR-T-cell therapy for relapsed or refractory multiple myeloma

B-Cell Maturation Antigen (BCMA) As a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma

An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis

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