Updated Perspectives on the Management of Multiple Myeloma in Older Patients: Focus on Lenalidomide

Abstract

Multiple myeloma is a hematologic malignancy that predominantly affects older adults, with a median age at diagnosis of 70 years old. A mainstay of multiple myeloma treatment is lenalidomide, which is an immunomodulatory drug (IMiD) that changed the treatment paradigm for multiple myeloma. This is particularly true for older adults who do not undergo autologous stem cell transplantation (ASCT). Several pivotal trials summarized in this review demonstrate the efficacy and safety of lenalidomide in older adults with multiple myeloma, including significant improvements in response rates, progression-free survival and overall survival in the first-line and relapsed/refractory settings. Potential adverse effects include venous thromboembolism, cytopenias, and second malignancies and the doses tolerated in real-world older patients are often lower than those utilized in clinical trials enrolling select older patients. Given the heterogeneity of aging, several approaches to measuring frailty have been developed and validated to aid in predicting which older adults may benefit from empiric dose reduction to reduce the risk of toxicity and improve the tolerability of treatment. A number of randomized trials have explored a range of approaches utilizing lenalidomide in older adults in both the up-front and relapsed setting, ranging from attenuated maintenance strategies through quadruplet combination therapies including proteasome inhibitors and monoclonal antibodies. This wealth of literature provides a great number of options, which can make it difficult for a clinician to determine a single optimal recommendation for an individual patient. While lenalidomide is currently part of standard of care, the treatment of multiple myeloma is growing rapidly. There is a need to expand clinical trials participation to older adults with multiple myeloma. Incorporation of validated comprehensive geriatric assessments in clinical trials for multiple myeloma could provide a more accurate depiction of the older patient population and is an area for future exploration.