Impact of frailty on infection risk in non-transplant eligible multiple myeloma patients: a systematic review and meta-analysis

Background Multiple myeloma (MM), a plasma-cell neoplasm predominantly diagnosed in the elderly, is profoundly influenced by patients’ frailty status. Yet, the precise relationship between this geriatric vulnerability and the risk of life‐threatening (grade 3–4) infections in autologous stem cell transplant (ASCT)‐ineligible MM cohorts remains largely uncharted. Methods We conducted a systematic review and meta‑analysis to uncover how frailty fuels infection risk in newly diagnosed multiple myeloma (NDMM) patients who are not eligible for ASCT. We included studies that classified participants as fit, intermediate, or frail and reported their infection outcomes. By comparing the risk of severe infections across these frailty categories, we exposed the hidden cost of this geriatric vulnerability. Results. Across six studies (n = 1,710), frailty afflicted 46.4% of patients. Non‑frail individuals experienced a 23% lower risk of severe infection than their frail counterparts (RR 0.77; 95% CI 0.66–0.90). In subgroup analyses, fit patients slashed their infection risk by 33% versus frail peers (RR 0.67; 95% CI 0.43–1.04), while those deemed intermediate registered a 14% reduction (RR 0.86; 95% CI 0.72–1.01). Directly comparing fit to intermediate categories yielded an RR of 0.85 (95% CI 0.51–1.40), spotlighting how even modest dips in resilience can tip the scales toward vulnerability. Conclusions. Frailty dramatically raises infection risk in ASCT‑ineligible NDMM patients, with the frailest facing the greatest danger. Even more striking, the intermediate group’s infection rates align more closely with the frail than the fit, suggesting our current mid‑tier label may be hiding serious vulnerability. These results underscore the urgency of embedding comprehensive frailty assessments into routine care and refining stratification tools to accurately flag high‑risk patients and enable truly personalized, preemptive infection management.