A safety review of recently approved and emerging drugs for patients with relapsed or refractory multiple myeloma

ABSTRACT

Introduction

Multiple new drugs have been approved over the past 5 years for the treatment of relapsed/refractory multiple myeloma (RRMM), and these are being increasingly widely used. Clinicians need to familiarize themselves with common toxicities associated with these drugs and with novel toxicities requiring specific management and supportive care.

Areas covered

We review common toxicities associated with agents approved for RRMM in the past 5 years, including the anti-CD38 monoclonal antibody isatuximab, the antibody–drug conjugate belantamab mafodotin, the bispecific antibody teclistamab, the chimeric antigen receptor (CAR) T cell products idecabtagene vicleucel and ciltacabtagene autoleucel, the selective inhibitor of nuclear export compound selinexor, and the drug–peptide conjugate melflufen, as well as toxicities associated with emerging agents for RRMM including additional bispecific antibodies, the BCL-2 inhibitor venetoclax, and the cereblon E3 ligase modulators iberdomide and mezigdomide. We searched the published literature using PubMed, plus congress abstracts, for the above list of drug names or classes and ‘myeloma.’

Expert opinion

Optimal management of toxicities associated with these recently approved and emerging therapies will be critical in maximizing clinical benefit and aiding widespread adoption in routine clinical practice. We summarize current recommendations and guidelines and provide expert insights into supportive care requirements.

KEYWORDS:

• Antibody–drug conjugate
• bispecific antibody
• CAR T cell therapy
• monoclonal antibody
• melflufen
• multiple myeloma
• selinexor
• supportive care

Article highlights

• Recently approved and emerging drugs for the treatment of relapsed/refractory multiple myeloma are associated with novel toxicities that require specific management and supportive care

• The anti-CD38 monoclonal antibody isatuximab has a manageable safety profile that reflects prior experience with daratumumab

• The antibody–drug conjugate belantamab mafodotin is specifically associated with ocular toxicity, particularly keratopathy, that requires regular eye examinations during each cycle of treatment

• T-cell-directing bispecific antibodies and the anti-BCMA CAR T-cell therapies ide-cel and cilta-cel are associated with cytokine release syndrome and neurotoxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), which require close monitoring and supportive care primarily with tocilizumab or corticosteroids

• Common toxicities associated with selinexor are qualitatively similar to, but can be more pronounced than, those already managed for other RRMM agents; these important toxicities can be managed with dose modification and aggressive supportive care

• Toxicities associated with melflufen are primarily hematologic, including high rates of grade ≥3 neutropenia, thrombocytopenia, and anemia

• Addition of venetoclax to bortezomib-dexamethasone results in higher rates of gastrointestinal toxicities and grade ≥3 neutropenia and pneumonia

• The common toxicities of iberdomide and mezigdomide appear to be aligned with those associated with lenalidomide and pomalidomide, including grade ≥3 hematologic toxicities and infections

• Healthcare professionals need to familiarize themselves with the safety profiles of these new agents as they begin to be used earlier in the treatment algorithm and thus more widely among patients with RRMM

Declaration of interests

S Midha has provided consultancy for Pfizer. MA Hartley-Brown has participated in advisory boards for AbbVie, BMS, Celgene, GSK, Janssen, Karyopharm, and Sanofi, and has received research funding from BMS/Celgene, GSK, and Sanofi. CC Mo has participated in advisory boards for AbbVie, BMS, GSK, Janssen, Karyopharm, Sanofi, and Takeda, and has provided consulting for AbbVie, Janssen, Karyopharm, and Sanofi. S Hossain has participated in an advisory board for Janssen. O Nadeem has participated in advisory boards for BMS, Janssen, GSK, Sanofi, and GPCR Therapeutics. Research funding from Takeda and Janssen. AS Sperling has provided consultancy for Novartis, Adaptive Biotechnologies, and Roche. PG Richardson has received grants to his institution for clinical trials from Bristol Myers Squibb/Celgene, Karyopharm, and Oncopeptides, and has served on advisory committees for Bristol Myers Squibb/Celgene, GSK, Karyopharm, Oncopeptides, Adaptive Biotechnologies, and Sanofi. 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.

Reviewer disclosures

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

Acknowledgments

The authors acknowledge Steve Hill, PhD, of Ashfield MedComms, an Inizio company, for medical writing and editing support, funded by Dana-Farber Cancer Institute and the RJ Corman Multiple Myeloma Research Fund.

Author contribution statement

PG Richardson developed the scope of the manuscript. All authors reviewed and revised the manuscript outline, first draft, and final draft, and approved the manuscript for submission.

Additional information

Funding

This paper was not funded.