Abstract
High-dose melphalan followed by autologous stem cell transplantation (ASCT) is the standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM). A substantial proportion of patients are deemed ineligible for ASCT due to age, comorbidities, performance status and/or frailty. Criteria defining transplant ineligibility remain inconsistent and poorly characterized. We conducted a systematic review that assessed phase II, III and IV randomized controlled trials (RCTs) through March 2025. We included a total of 55 studies that enrolled transplant-ineligible/deferred NDMM patients. Among 55 transplant-ineligible trials, only 47% explicitly defined ineligibility criteria. Of these, 44% of trials used age as a cut-off with/without other criteria. Only two studies explicitly specified which comorbidities constituted transplant ineligibility. When age was utilized as a cut-off, age ≥65 was the most commonly used cut-off. The median age of participants in these trials ranged from 62 years to 78.5 years and showed a trend upwards over time (p = 0.1388). Performance status of enrolled patients was reported inconsistently. Frailty tools were reported in 22% of studies. RCTs enrolling transplant-ineligible patients with NDMM demonstrated considerable heterogeneity in defining ineligibility. While the decision to pursue ASCT remains individualized, the absence of evidence-based definitions of transplant ineligibility complicates research interpretation and clinical decision-making.