High-dose melphalan supported by autologous transplantation has been the standard of care for eligible patients with newly diagnosed multiple myeloma for nearly 30 years. Several randomized clinical trials have reaffirmed the strong position of transplant in the era of triplets combining proteasome inhibitors, immunomodulatory drugs, and dexamethasone. Although quadruplets are becoming the standard in transplantation programs, no data are currently available on the need for a transplant with new regimens incorporating anti-CD38 monoclonal antibodies. Outcomes remain heterogeneous, with different response depths and durations depending on the cytogenetics at diagnosis. The improvement of disease prognostication using sensitive and specific tools allows for adapting the strategy to initial and dynamic risks. This review examines which patients need a transplant, when transplantation is preferable, and why.

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