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Novel immunotherapies in multiple myeloma - chances and challenges.

ABSTRACT: 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.

SUBMITTER: Rasche L

PROVIDER: S-EPMC8485654 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Novel immunotherapies in multiple myeloma - chances and challenges.

Rasche Leo L Wäsch Ralph R Munder Markus M Goldschmidt Hartmut H Raab Marc S MS

Haematologica 20211001 10

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 immunotherapi ...[more]

PMID: 34196164

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Project description:Whereas the treatment of MM was dependent solely on alkylating agents and corticosteroids during the prior three decades, the landscape of therapeutic measures to treat the disease began to expand enormously early in the current century. The introduction of new classes of small-molecule drugs, such as proteasome blockers (bortezomib and carfilzomib), immunomodulators (lenalidomide and pomalidomide), nuclear export inhibitors (selinexor), and histone deacetylase blockers (panobinostat), as well as the application of autologous stem cell transplantation (ASCT), resulted in a seismic shift in how the disease is treated. The picture changed dramatically once again starting with the 2015 FDA approval of two monoclonal antibodies (mAbs) - the anti-CD38 daratumumab and the anti-SLAMF7 elotuzumab. Daratumumab, in particular, has had a great impact on MM therapy and today is often included in various regimens to treat the disease, both in newly diagnosed cases and in the relapse/refractory setting. Recently, other immunotherapies have been added to the arsenal of drugs available to fight this malignancy. These include isatuximab (also anti-CD38) and, in the past year, the antibody-drug conjugate (ADC) belantamab mafodotin and the chimeric antigen receptor (CAR) T-cell product idecabtagene vicleucel (ide-cel). While the accumulated benefits of these newer agents have resulted in a doubling of the disease's five-year survival rate to more than 5 years and improved quality of life, the disease remains incurable. Almost without exception patients experience relapse and/or become refractory to the drugs used, making the search for innovative therapies all the more essential. This review covers the current scope of anti-myeloma immunotherapeutic agents, both those in clinical use and on the horizon, including naked mAbs, ADCs, bi- and multi-targeted mAbs, and CAR T-cells. Emphasis is placed on the benefits of each along with the challenges that need to be overcome if MM is to be considered curable in the future.

Dataset Information

Novel immunotherapies in multiple myeloma - chances and challenges.

Publications

Novel immunotherapies in multiple myeloma - chances and challenges.

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