30 Years of Improved Survival in Non-Transplant-Eligible Newly Diagnosed Multiple Myeloma

SIMPLE SUMMARY: Multiple myeloma mainly affects the elderly, who are usually not eligible to intensive treatments such as autologous stem cell transplant. Historically, the survival of these patients was short and there were few therapeutic options. Alkylating agents were the main options available until the 2000’s with a relatively low efficacy. However, the last years were marked by the emergence of numerous anti-myeloma drugs, especially with the rise of immunotherapy and targeted treatments. Older patient largely benefited from these advances in the field and therefore their survival has greatly increased. In this review, we summarized the progress made throughout the years in the treatment of older patients affected by multiple myeloma, starting from chemotherapy to innovative immune-based molecules. ABSTRACT: The treatment of multiple myeloma (MM) has greatly evolved these past few years. Recent advances in therapeutics have largely benefited elderly patients now renamed “non-transplant-eligible” (NTE) patients. Since the 1960s, and for several decades, chemotherapy was the only treatment for MM. Then, the field was marked by the emergence of targeted therapies in the 2000s, such as immunomodulating agents (thalidomide, lenalidomide, and pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), which were the first steps towards an increase in survival. Thereafter, the apparition of monoclonal antibodies (mAbs) was considered a milestone in the treatment of MM for both transplant-eligible and NTE patients. Anti-CD38 mAbs can be safely administered to older patients with an impressive efficacy leading to a never-achieved-before survival rate with the triple association of anti-CD38 mAbs, lenalidomide, and dexamethasone. However, progress is still expected with the introduction in the armamentarium for NTE patients of the most recent innovative immunotherapy-based treatments newly introduced in MM, e.g., CAR-T cells and bispecific antibodies. These “improved versions” of immune-based treatments will probably also benefit NTE patients, although further studies will be needed to better understand their role in this population.