More intensive therapy as more effective treatment for frail patients with multiple myeloma.

Although RCT data suggest that the more intensive triplet bortezomib-lenalidomide-dexamethasone (VRd) is superior to the less intensive doublet lenalidomide-dexamethasone (Rd) in patients newly diagnosed with multiple myeloma (MM), guidelines have historically recommended Rd over VRd for frail patients who may not tolerate a triplet. We identified 2573 patients (median age 69.7 years) newly diagnosed with MM who were initiated on VRd (990) or Rd (1583) in the national U.S. Veterans Affairs Healthcare System from 2004 to 2020. We measured frailty using the Veterans Affairs Frailty Index (VA-FI). To reduce imbalance in confounding, we matched patients on MM stage and 1:1 on a propensity score. Compared to nonfrail patients, moderate-severely frail patients had a higher prevalence of stage III MM and myeloma-related frailty deficits. VRd vs. Rd was associated with lower mortality (HR = 0.81, 95% CI = 0.70 - 0.94) in the overall matched population. Moderate-severely frail patients demonstrated the strongest association (HR 0.74, 95% CI 0.56 - 0.97), whereas the association weakened in mildly frail (HR 0.80, 95% CI 0.61 - 1.05) and nonfrail patients (HR 0.86, 95% CI 0.67 - 1.10). VRd vs. Rd was associated with a modestly higher incidence of hospitalizations in the overall population, but this association weakened in moderate-severely frail patients. Our findings confirm the benefit of VRd over Rd in U.S. veterans and further suggest that this benefit is strongest in patients with the highest levels of frailty, arguing that more intensive treatment of myeloma may be more effective treatment of frailty itself.