Outcomes of Patients with Newly Diagnosed Transplant-Ineligible Multiple Myeloma According to Clinical Trials Enrollment: Experience of a Single Institution

SIMPLE SUMMARY: Clinical trials (CTs) may not always reflect real-world medical practice, particularly in non-transplant-eligible (NTE) newly diagnosed multiple myeloma (NDMM) patients due to stringent recruitment criteria. Our objective was to assess exclusion rates, reasons, and survival outcomes for NTE NDMM patients in and out of CTs. Roughly 50% did not meet eligibility criteria, mainly due to comorbidities, poor ECOG-PS, or renal failure. CT participation correlated with higher overall response rates (ORRs), improved progression-free survival (PFS) and overall survival (OS), especially in recent years. A slight PFS extension associated with a substantial improvement in OS in CT patients suggested a selection bias. Excluded patients did not experience improved survival, with the median OS remaining unchanged from 2003 to 2017. These findings emphasize that CT participants may not fully represent the wider NDMM population in real-world clinical practice. It is essential to exercise caution when applying CT results to routine care settings, recognizing the limitations of generalization. ABSTRACT: The proportion of non-transplant-eligible (NTE) newly diagnosed multiple myeloma (NDMM) patients excluded from clinical trials (CTs) and their prognosis is unknown. CT results may not be generalizable to real-world practice due to strict recruitment criteria. We analyzed causes of NTE-NDMM patient exclusion form CTs and their outcomes. A total of 211 NTE-NDMM patients were included. They were divided into three periods: 2003–2007, 2008–2012, and 2013–2017. Overall, 50% received non-trial treatment (NCT), while 50% participated in a CT (20% control group (CG) and 30% experimental group (EG)). Main causes for exclusion from CTs were comorbidities, ECOG > 2, and renal insufficiency. In the first two periods, the CR rate was similar regardless of treatment type, but in the last period, the EG group showed improved CR. Median PFS was similar in the first two periods, with a benefit seen only in the EG in the last period. The median OS was significantly longer in CT-included patients compared to NCT group in the last two periods. Conclusions: The presence of comorbidities and worsened ECOG were the main reasons for CT exclusion. Patients included in CTs had a longer OS than NCT. This OS benefit may be influenced by a selection bias, making it challenging to generalize CT results to real clinical practice.