# Inconsistent definitions of transplant ineligibility in multiple myeloma: A systematic review

## TL;DR

This study finds that there is no consistent way to decide who is too sick for a stem cell transplant in multiple myeloma patients.

## Contribution

The study systematically reviews how transplant ineligibility is inconsistently defined in clinical trials for multiple myeloma.

## Key findings

- Only 47% of 55 trials explicitly defined transplant ineligibility criteria.
- Age ≥65 was the most common cut-off, but performance status and comorbidities were inconsistently reported.
- Frailty tools were used in only 22% of studies, highlighting a lack of standardized criteria.

## 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.

This systematic review of 55 trials reveals significant inconsistency in defining transplant ineligibility for multiple myeloma. Arbitrary age cut‐offs predominantly drive exclusion, while validated frailty tools and specific comorbidities are frequently underutilized. Standardized, evidence‐based criteria are essential to optimize patient selection and improve clinical decision‐making.