Multiple myeloma treatment has evolved significantly over the past two decades, leading to improvements in progression-free and overall survival. Nonetheless, a significant challenge has emerged with the rising incidence of secondary neoplasms (SNs), including myeloid and lymphoid malignancies1, 2, 3. These malignancies are often therapy-related and associated with prior cytotoxic therapy, radiation, and prolonged maintenance treatment. As MM survival improves, understanding the spectrum, timing, and pathogenesis of therapy-related secondary neoplasms has become increasingly important. While previous studies have reported varying incidence rates of t-MDS/AML and secondary lymphomas following MM therapy, few have comprehensively analyzed these outcomes in a real-world cohort. Furthermore, the specific contributions of different therapeutic agents and transplant protocols to the risk of secondary neoplasms remain incompletely defined.

This review paper aims to report on the incidence and types of secondary hematologic malignancies that occur in patients treated for MM, focusing on the impact of High dose- autologous stem cell transplant (HD-ASCT) and maintenance therapy as contributing factors. We also explore possible pathogenic mechanisms linking MM therapy to secondary neoplasms, with emphasis on stem cell damage, clonal evolution, and mutagenesis.