Advances in the Treatment of Newly Diagnosed Multiple Myeloma: Current Status and Future Directions

Multiple myeloma (MM) is a hematologic malignancy characterized by frequent relapses and ultimately acquired resistance to therapy across sequential lines of treatment. Nevertheless, treatment options are evolving rapidly, with the introduction of novel agents and immune-based therapies that deepen responses, prolong remission durations and improve survival as well as quality of life, thereby markedly improving patient outcomes. The current management of MM involves a multidrug-class strategy tailored by transplant eligibility, frailty, cytogenetic, clinical and molecular risk stratification, with quadruplet regimens set to become the standard of care in newly diagnosed MM (NDMM). These combinations include immunomodulatory drugs, proteasome inhibitors, anti-CD38 monoclonal antibodies and corticosteroids, and, in selected settings, alkylating agents, with this approach now being increasingly tailored to each individual patient. Additionally, novel treatment approaches, such as chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, have gained regulatory approval in the relapsed/refractory setting and are now being integrated into earlier lines of therapy. This review summarizes recent clinical trial data and evolving therapeutic strategies in NDMM, including response-adapted and minimal residual disease (MRD)-guided approaches, regimens based on the anti-CD38 monoclonal antibodies daratumumab and isatuximab, the bispecific antibodies teclistamab, elranatamab and linvoseltamab, the antibody-drug conjugate belantamab mafodotin, the next-generation cereblon E3 ligase modulatory drug (CELMoD) iberdomide, as well as cytogenetic and molecular determinants of treatment outcomes. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Ji Hyun Lee, Division of Hematology-Oncology, Department of Internal Medicine, Dong-A University College of Medicine, Busan, Republic of Korea One anonymous peer reviewer Received on March 17, 2026; accepted after peer review on May 12, 2026; published online on May 19, 2026.