Newly Diagnosed High‐Risk Multiple Myeloma: Outcomes and Management

Multiple myeloma (MM) is a heterogeneous hematologic malignancy, with high-risk cytogenetic abnormalities (HRCAs) such as del(17p), t(4; 14), t(14; 16), and gain(1q) contributing to poor prognosis in approximately 20%-25% of newly diagnosed patients. These abnormalities are associated with aggressive disease, frequent relapses, and inferior progression-free and overall survival. This review explores the evolving therapeutic landscape for high-risk MM, focusing on induction strategies for both transplant-eligible and transplant-ineligible patients, the role of autologous stem cell transplantation (ASCT), and the use of consolidation and maintenance therapies. Emerging modalities such as bispecific antibodies and chimeric antigen receptor T-cell (CAR-T) therapies are examined, particularly in the context of their integration into earlier lines of treatment. Quadruplet induction regimens incorporating proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have shown promise in improving outcomes and are becoming a cornerstone of frontline therapy. The review also emphasizes the potential of personalized, risk-adapted approaches based on cytogenetic profiling and minimal residual disease (MRD) monitoring. Ongoing clinical trials investigating the early use of CAR-T cells and bispecific antibodies may further transform the standard of care for patients with high-risk MM.