Toxicity management strategies for next-generation novel therapeutics in multiple myeloma

Abstract

The therapeutic options available for patients with multiple myeloma have greatly expanded over the past decade and incorporating these novel agents into routine clinical practice has significantly improved outcomes. The next generation of therapeutics is available for relapsed and refractory patients either as standard of care or in clinical trial, and these drugs represent a generational paradigm shift. Patients now have access to a multitude of novel immunotherapeutics, including monoclonal antibodies, an antibody–drug conjugate, chimeric antigen receptor T-cells (CAR-T), and bispecific T-cell redirecting antibodies, and novel oral therapies including selinexor (selective inhibitor of nuclear export) and venetoclax (bcl-2 inhibitor). While these drugs have the potential to be highly efficacious in certain subsets of patients when used as single agents or in combination regimens, they are each associated with unique toxicity profiles. It is imperative to understand these potential adverse events to ensure patient safety. Appropriate supportive care management is paramount to maximize drug exposure and therapeutic efficacy. The following review focuses its discussion on drugs and combination regimens that are currently FDA-approved and those that continue to be investigated in clinical trials, highlights the clinically relevant toxicity profiles for each of the different agents, and provides practical considerations for the treatment team.

The Effect of Belantamab Mafodotin on Primary Myeloma–Stroma Co-Cultures: Asymmetrical Mitochondrial Transfer between Myeloma Cells and Autologous Bone Marrow Stromal Cells

“…However, with the introduction of novel therapies into the standard of care in the recent decade, such as second-generation proteasome inhibitors (carfilzomib, ixazomib), third-generation immunomodulatory drugs (pomalidomide), HDAC inhibitors (panobinostat), monoclonal antibodies (daratumumab, isatuximab, elotuzumab), and the BCL-2 inhibitor venetoclax, approximately 90% of myeloma patients have a considerable chance of reaching complete remission and measurable residual disease negativity [ 4 , 29 , 30 ]. Moreover, the latest therapies including bispecific antibodies, antibody–drug conjugates, and chimeric antigen receptor T cells show promising efficacy even for multi-refractory patients with high-risk features and may help to achieve and maintain deep and highly durable responses [ 6 , 31 , 32 , 33 ].…”

Adverse Event Reporting in Randomized Clinical Trials for Multiple Myeloma

“…These treatments can result in considerable toxic effects that negatively affect patient quality of life . Multiple myeloma therapies, although effective, may be associated with unpleasant adverse effects ranging from weakness, fatigue, nausea, and diarrhea to more serious adverse events (SAEs) such as permanent neuropathy, cytopenias, life-threatening infections and bleeding events, and even death in some cases . In a disease such as MM in which treatment is often given continuously over longer periods (often for years, as maintenance therapy), toxic effects and tolerability become even more important.…”

“… 2 Multiple myeloma therapies, although effective, may be associated with unpleasant adverse effects ranging from weakness, fatigue, nausea, and diarrhea to more serious adverse events (SAEs) such as permanent neuropathy, cytopenias, life-threatening infections and bleeding events, and even death in some cases. 3 , 4 , 5 , 6 , 7 , 8 In a disease such as MM in which treatment is often given continuously over longer periods (often for years, as maintenance therapy), toxic effects and tolerability become even more important.…”

Teclistamab for Multiple Myeloma: Clinical Insights and Practical Considerations for a First-in-Class Bispecific Antibody

“…[62][63][64] With grade 1 ICANS, seizure prophylaxis with levetiracetam should be initiated while dexamethasone can be considered. 65 For grade 2 or higher ICANS, patients should receive full neurologic evaluations along with high doses of steroids (potential regimens include 10-20 mg dexamethasone IV every 6 hours for grades 2-3, 1-2 g IV methylprednisolone daily for grade 4) with a rapid taper once symptoms improve. 61 The Future of T Cell-Engaging Antibodies in Myeloma…”