Teaming up for CAR-T cell therapy

Wäsch, Ralph; Munder, Markus; Marks, Reinhard

doi:10.3324/haematol.2019.228676

Cited by 8 publications

(9 citation statements)

References 18 publications

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“…Despite numerous autologous CAR-T products under development 67,68 and encouraging high response rates, 69 none have yet been approved, with BCMA remaining the best evaluated target. 49,51,69 Other limitations are toxicities, resistance mechanisms, availability, and patient management (Table 4).…”

Section: Improving Chimeric Antigen Receptor T-cell Therapies In Multiple Myelomamentioning

confidence: 99%

European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma

Bruno¹,

Wäsch

Engelhardt

et al. 2021

haematol

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Chimeric antigen receptor (CAR) T cells (CAR-T) have dramatically changed the treatment landscape of B-cell malignancies, providing a potential cure for relapsed/refractory patients. Long-term responses in patients with acute lymphoblastic leukemia and non Hodgkin lymphomas have encouraged further development in myeloma. In particular, B-cell maturation antigen (BCMA)-targeted CAR-T have established very promising results in heavily pre-treated patients. Moreover, CAR-T targeting other antigens (i.e., SLAMF7 and CD44v6) are currently under investigation. However, none of these current autologous therapies have been approved, and despite high overall response rates across studies, main issues such as long-term outcome, toxicities, treatment resistance, and management of complications limit as yet their widespread use. Here, we critically review the most important pre-clinical and clinical findings, recent advances in CAR-T against myeloma, as well as discoveries in the biology of a still incurable disease, that, all together, will further improve safety and efficacy in relapsed/refractory patients, urgently in need of novel treatment options.

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Section: Improving Chimeric Antigen Receptor T-cell Therapies In Multiple Myelomamentioning

confidence: 99%

European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma

Bruno¹,

Wäsch

Engelhardt

et al. 2021

haematol

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“…The main toxicities are CRS, immune effector cell-associated neurotoxicity syndrome (ICANS) and cytopenia, which may be prolonged. 41,42 There has recently been progress in developing CAR T cells to treat MM. 43 T cells are harvested by an unstimulated leukapheresis and genetically modified to generate CAR T cells using a lentiviral or retroviral fusion-construct with an antibody fragment to recognize the tumor antigen and the T cell receptor signaling domain CD3ζ to activate the modified T-cell (first generation).…”

Section: Chimeric Antigen Receptor T-cell Approachesmentioning

confidence: 99%

“…The main toxicities are CRS, immune effector cell-associated neurotoxicity syndrome (ICANS) and cytopenia, which may be prolonged. 41 , 42 …”

Section: Chimeric Antigen Receptor T-cell Approachesmentioning

confidence: 99%

Novel immunotherapies in multiple myeloma – chances and challenges

et al. 2021

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In this review article, we summarize the latest data on antibody-drug conjugates, bispecific T-cell-engaging antibodies, and chimeric antigen receptor T cells in the treatment of multiple myeloma. We discuss the pivotal questions to be addressed as these new immunotherapies become standard agents in the management of multiple myeloma. We also focus on the selection of patients for these therapies and speculate as to how best to individualize treatment approaches. We see these novel immunotherapies as representing a paradigm shift. However, despite the promising preliminary data, many open issues remain to be evaluated in future trials.

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“…Bispecific antibodies or T-cell engagers (BiTEs) link T-cells by binding CD3 and surface antigens of myeloma cells such as BCMA and result in T-cell activation and myeloma cell death. Encouraging targets include GPRC5D or FcRH5 [71,[81][82][83][84][85]. The cereblon E3 ligase modulators CC-92480 and iberdomide are currently tested in pre-treated RRMM patients.…”

Section: Second/subsequent Relapsementioning

confidence: 99%

Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors

Gengenbach

Graziani

Reinhardt

et al. 2021

Cancers

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Treatment of relapsed/refractory multiple myeloma (RRMM) is more complex today due to the availability of novel therapeutic options, mostly applied as combination regimens. immunotherapy options have especially increased substantially, likewise the understanding that patient-, disease- and treatment-related factors should be considered at all stages of the disease. RRMM is based on definitions of the international myeloma working group (IMWG) and includes biochemical progression, such as paraprotein increase, or symptomatic relapse with CRAB criteria (hypercalcemia, renal impairment, anemia, bone lesions). When choosing RRMM-treatment, the biochemical markers for progression and severity of the disease, dynamic of disease relapse, type and number of prior therapy lines, including toxicity and underlying health status, need to be considered, and shared decision making should be pursued. Objectively characterizing health status via geriatric assessment (GA) at each multiple myeloma (MM) treatment decision point has been shown to be a better estimate than via age and comorbidities alone. The well-established national comprehensive cancer network, IMWG, European myeloma network and other national treatment algorithms consider these issues. Ideally, GA-based clinical trials should be supported in the future to choose wisely and efficaciously from available intervention and treatment options in often-older MM adults in order to further improve morbidity and mortality.

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Teaming up for CAR-T cell therapy

Cited by 8 publications

References 18 publications

European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma

European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma

Novel immunotherapies in multiple myeloma – chances and challenges

Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors

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