Management of Adverse Events Associated with Pomalidomide-Based Combinations in Patients with Relapsed/Refractory Multiple Myeloma

Simple Summary: Pomalidomide is one of three immunomodulatory (IMiD (R)) agents approved for the treatment of multiple myeloma. Despite providing survival benefits, IMiD agents have distinct but overlapping safety profiles. These safety profiles should be considered at the treatment selection stage and when monitoring and managing adverse events to help patients adhere to their treatments, therefore maximizing their effectiveness and helping to maintain quality of life. Here, we discuss common adverse events associated with pomalidomide and present five clinically relevant hypothetical case studies in patients with relapsed/refractory multiple myeloma. We discuss factors impacting treatment selection and provide guidance on how to mitigate and manage adverse events based on published evidence and clinical experience. We also offer future perspectives by briefly discussing targeted protein degraders, a new class of medications currently being studied in clinical trials for the treatment of myeloma that build upon the well-established IMiD agent platform. Multi-agent regimens incorporating immunomodulatory (IMiD (R)) agents such as thalidomide, lenalidomide, and pomalidomide have become the preferred standard of care for the treatment of patients with multiple myeloma (MM), resulting in improved survival outcomes. Currently, there are three IMiD agents approved for the treatment of MM: thalidomide, lenalidomide, and pomalidomide. Lenalidomide is commonly used to treat patients with newly diagnosed MM and as maintenance therapy following stem cell transplant or after disease relapse. Pomalidomide, the focus of this review, is approved in patients with relapsed/refractory MM (RRMM). Despite survival benefits, IMiD agents each have different safety profiles requiring consideration both prior to starting therapy and during treatment. Adverse event (AE) management is essential, not only to ensure treatment adherence and thus ensure optimal efficacy but also to maintain patient quality of life. Here, we discuss AEs associated with pomalidomide and present five clinically relevant hypothetical case studies in patients with RRMM to provide scenario-driven guidance regarding treatment selection and AE prevention and management in the clinical setting. Lastly, as new treatment approaches continue to be explored in MM, we also discuss novel cereblon E3 ligase modulator (CELMoD (TM)) agents including iberdomide (CC-220) and mezigdomide (CC-92480).