Emerging role of CAR T cell therapy in multiple myeloma

Nair, Ranjit; Patel, Krina

doi:10.1002/acg2.22

Cited by 2 publications

(1 citation statement)

References 32 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous targeted immunotherapies are currently in development for the treatment of multiple myeloma with mechanisms of action that may offer significant advantages over (or complementarity with) available treatments (45). Notable amongst them are chimeric antigen receptor T-cell therapies targeted at the B-cell maturation antigen (BCMA) multiple myeloma antigen that have demonstrated remarkable responses in heavily pretreated relapsed/refractory patients, including high proportions of patients with complete clinical responses accompanied by MRD negativity (46,47), as well as BCMA-directed T-cell engager therapeutics with promising clinical potential (48)(49)(50).…”

Section: Future Immunotherapies For Multiple Myelomamentioning

confidence: 99%

Targeting Multiple Myeloma with AMG 424, a Novel Anti-CD38/CD3 Bispecific T-cell–recruiting Antibody Optimized for Cytotoxicity and Cytokine Release

Zafra

Fajardo

Zhong

et al. 2019

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Despite advances in the treatment of multiple myeloma, new therapies are needed to induce more profound clinical responses. T-cell-redirected lysis triggered by bispecific antibodies recruiting T cells to cancer cells is a clinically validated mechanism of action against hematologic malignancies and CD38 is a tumor-associated antigen with near-universal expression in multiple myeloma. Thus, an anti-CD38/CD3 bispecific T-cell-recruiting antibody has the potential to be an effective new therapeutic for multiple myeloma. Experimental Design: Anti-CD38/CD3 XmAb T-cellrecruiting antibodies with different affinities for CD38 and CD3 were assessed in vitro and in vivo for their redirected T-cell lysis activity against cancer cell lines, their lower levels of cytokine release, and their potency in the presence of high levels of soluble CD38. Select candidates were further tested in cynomolgus monkeys for B-cell depletion and cytokine release properties. Results: AMG 424 was selected on the basis of its ability to kill cancer cells expressing high and low levels of CD38 in vitro and trigger T-cell proliferation, but with attenuated cytokine release. In vivo, AMG 424 induces tumor growth inhibition in bone marrow-invasive mouse cancer models and the depletion of peripheral B cells in cynomolgus monkeys, without triggering excessive cytokine release. The activity of AMG 424 against normal immune cells expressing CD38 is also presented. Conclusions: These findings support the clinical development of AMG 424, an affinity-optimized T-cell-recruiting antibody with the potential to elicit significant clinical activity in patients with multiple myeloma.

show abstract

Section: Future Immunotherapies For Multiple Myelomamentioning

confidence: 99%

Targeting Multiple Myeloma with AMG 424, a Novel Anti-CD38/CD3 Bispecific T-cell–recruiting Antibody Optimized for Cytotoxicity and Cytokine Release

Zafra

Fajardo

Zhong

et al. 2019

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

Efficacy and safety of venetoclax in patients with relapsed/refractory multiple myeloma: a meta-analysis

Gao,

Zeng,

Zhao

et al. 2023

BMC Cancer

View full text Add to dashboard Cite

Background Venetoclax is clinically active in treating relapsed/refractory multiple myeloma (RRMM). This study evaluated the efficacy and safety of venetoclax or venetoclax with other agents in treating RRMM. Methods PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched. We included studies investigating the efficacy and safety of venetoclax or venetoclax with other agents in treating RRMM. Overall response rates (ORR), stringent complete response rates (sCR), complete response rates (CR), very good partial response rates (VGPR), partial response rates (PR), stable disease (SD), progressive disease (PD) and adverse events were synthesized using either a random-effects model or a fixed-effects model. Results A total of 7 clinical trials with 482 patients with RRMM were included. Concerning venetoclax with other agents, the pooled ORR, sCR, CR, VGPR, PR, SD, and PD were 0.76 (95% CIs: 0.62, 0.87), 0.11 (95% CIs: 0.04, 0.21), 0.18 (95% CIs: 0.11, 0.26), 0.16 (95% CIs: 0.12, 0.25), 0.29 (95% CIs: 0.25, 0.34), 0.07 (95% CIs: 0.05, 0.10), and 0.11 (95% CIs: 0.04, 0.23). The overall rate of adverse events ≥ Grade 3 was 0.84 (95% CIs: 0.77, 0.91). The most common non-hematologic adverse events were nausea, diarrhea, fatigue, back pain, and vomiting; hematologic adverse events included thrombocytopenia, neutropenia, anemia, leukopenia, and lymphopenia. Conclusions This study indicates that venetoclax alone or in combination with other agents reveals favorable treatment responses and acceptable adverse events in treating RRMM.

show abstract

Emerging role of CAR T cell therapy in multiple myeloma

Cited by 2 publications

References 32 publications

Targeting Multiple Myeloma with AMG 424, a Novel Anti-CD38/CD3 Bispecific T-cell–recruiting Antibody Optimized for Cytotoxicity and Cytokine Release

Targeting Multiple Myeloma with AMG 424, a Novel Anti-CD38/CD3 Bispecific T-cell–recruiting Antibody Optimized for Cytotoxicity and Cytokine Release

Efficacy and safety of venetoclax in patients with relapsed/refractory multiple myeloma: a meta-analysis

Contact Info

Product

Resources

About