Guest Editor: Pellegrino Musto HOW FIRST LINE THERAPY IS CHANGING IN TRANSPLANT-ELIGIBLE MULTIPLE MYELOMA PATIENTS

Multiple myeloma is a malignant haematological neoplasm characterized by the proliferation of plasma cells in the bone marrow. Each year, over 35,000 new cases are diagnosed in the United States, and nearly 13,000 patients die from the disease¹. The main cause of morbidity is bone disease, characterized by osteolytic lesions, which, unlike other malignancies that metastasize to bone, are not followed by new bone formation². Other major clinical manifestations include anemia, hypercalcemia, renal failure, and an increased risk of infections. Approximately 1-2% of patients present with extramedullary disease (EMD) at the time of diagnosis, while 8% develop EMD later in the course of the disease³.

Although multiple myeloma remains incurable, its treatment continues to evolve rapidly. Approved therapies include immunomodulatory agents (IMiDs, such as thalidomide, lenalidomide, and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), and monoclonal antibodies (mAb) targeting CD38 (especially daratumumab and isatuximab) and SLAMF7. New therapeutic avenues include bispecific antibodies and chimeric antigen receptor T-cell (CAR-T) therapy^4-5.

The latest ESMO (European Society for Medical Oncology)⁶ and NCCN (National Comprehensive Cancer Network) guidelines⁷ have set the standard of care for patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation, particularly those in good general condition and < 70 years old. This approach is divided in four phases: induction therapy, hematopoietic stem cell collection and autologous transplant, consolidation, and maintenance. The most significant differences between the guidelines occur during the induction phase, influenced by regulatory approvals in the United States and Europe.

This article will focus on the changing landscape of therapies for newly diagnosed multiple myeloma (NDMM) in transplant-eligible (TE) patients and how the trend is increasingly focusing on therapies targeting minimal residual disease (MRD) and baseline risk stratification.