SOHO State of the Art Updates and Next Questions | Late/Deferred ASCT in Myeloma

High-dose melphalan with autologous stem cell transplant (HDM-ASCT) remains a standard-of-care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), with data from randomized studies demonstrating progression-free survival (PFS) benefit with transplant versus nontransplant approaches. However, with increasing overall survival (OS) in this setting, associated with the substantial efficacy of triplet and quadruplet regimens and multiple novel treatment approaches, strategic considerations are key, together with a holistic approach taking into account patients' preferences and needs, for treatment decision-making. In this context, the approach of deferring HDM-ASCT is being increasingly considered, associated with various drivers. Rationales for deferring HDM-ASCT include the acute and long-term toxicities and sequelae associated with undergoing transplant, such as the increased mutational burden and elevated risk of secondary leukemia arising following HDM. Given these downsides, another driver for considering deferred HDM-ASCT is that substantial variability in magnitude of PFS benefit has been seen across patient subgroups. Furthermore, despite significant PFS benefit, randomized studies have not shown OS benefit in the era of triplet induction/consolidation and multiple active treatment options at relapse. Additionally, very high rates of minimal residual disease (MRD)-negative responses have been demonstrated with emerging standard-of-care quadruplet induction regimens for NDMM, facilitating potential HDM-ASCT-sparing, MRD-adapted treatment approaches. Finally, novel therapies such as chimeric antigen receptor (CAR) T-cell and bispecific antibody therapies are beginning to be investigated as upfront alternatives in transplant-eligible patients. Thus, associated with these multiple drivers, late or deferred HDM-ASCT is emerging as a potential standard-of-care approach for select transplant-eligible patients with NDMM.