On the continuous (R)evolution of antibody-based and CAR T cell therapies in multiple myeloma: an early 2022 glance into the future

ABSTRACT

Introduction

The pace at which the identification of novel therapeutic targets has led to the approval of multiple myeloma (MM) agents during the last two decades is nothing more than spectacular. Nevertheless, MM remains an incurable disease. Therefore, there is an urgent need for additional, innovative therapeutics. Immune dysfunction and the tumor-permissive immune bone marrow microenvironment represent hallmarks of MM pathophysiology. Naked monoclonal antibodies directed against SLAMF7 and CD38 already constitute backbones of today’s MM therapy. Novel immunotherapeutic modalities including antibody-drug-conjugates (ADC), bispecific antibodies (BsAb), and chimeric-antigen-receptor T cells are on the way to once more revolutionize future MM therapy.

Areas covered

The present review article summarizes the most recent results on MM immunotherapies presented at the 2021 Annual Meeting of the American Society of Hematology; and throws a glance on ongoing preclinical and clinical efforts aiming at further increasing their efficacy, while reducing their toxicity.

Expert opinion

With the approvals of the first-in-class BCMA-targeting ADC (belantamab mafodotin) and two BCMA-targeting CAR T cell products (Ide-cel, Cilta-cel); and the approval of the first-in-class BCMAxCD3 BsAb immediately pending, the era of modern next-generation immunotherapies in MM is continuously evolving. Long-term disease-free survival and potential cure of MM are finally within reach.

KEYWORDS:

• Multiple myeloma
• monoclonal antibodies
• antibody-drug-conjugates
• Car T-cells
• bispecific antibodies

Article highlights

• CD38-containing VRd induction regimens (Isa-VRd, Dara-VRd) are evolving as the new standard of care for TE-NDMM patients

• besides VRd, Dara-Rd is the new standard of care for NTE NDMM patients

• cilta-cel is the second BCMA-targeted CAR T cell product that has been approved most recently for the treatment of RRMM patients

• teclistamab will become the first BsAb to be approved for MM therapy

• non-BCMA-BsAbs (talquetamab, cevostamab) and non-BCMA CAR T cells already herald the post-BCMA era

This box summarizes key points contained in the article.

Disclosures

SV received speaker’s honoraria from Bristol Myers Squibb, MSD, Pfizer, and consultancy fees from Roche, Eusa, MSD, and Merck; KP has received speaker’s honoraria from Celgene, Amgen Inc. and Janssen Pharmaceuticals, consultancy fees from Celgene, Takeda and Janssen Pharmaceuticals, and research support from Roche Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The remaining authors declare no conflict of interest.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.This investigation was supported by the WST3-F-5031 298/003-2019 (KP) and the Life Science grant LSC18-010 (SV and KP). KP and MP are recipients of a research support grant from Roche Pharmaceuticals.