Abstract
Introduction: New treatments offer hope for patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT), such as older patients and those with a higher comorbidity burden or frailty. Data on current first-line treatment patterns among transplant-ineligible (TIE) NDMM patients in the US who are older, who are frail, or who have a high comorbidity burden can inform comparison group selection for clinical trials of novel treatments that include these populations.
Methods: Patients with TIE NDMM were identified using two US health insurance claims databases, Optum Clinformatics® (Optum) (Jun 2019 – Dec 2024) and HealthVerity (HV) (Jun 2019 – Apr 2025). Patients were included if they had a first-ever multiple myeloma ICD diagnosis code (C90.00) and had ≥365 days continuous enrollment before and after diagnosis. They were classified as TIE if they did not receive HSCT in the 365 days after diagnosis. Comorbidities and frailty indicators were identified in the 365 days prior to diagnosis. Regimens were categorized using an algorithm. Patient frailty was evaluated using the Faurot Frailty Index, a proxy for frailty using indicators of activities of daily living; patients were categorized by common cut-points into fit (<0.1), fit frail (0.1-<0.2), frail (0.2-0.4), and severely frail (≥0.4). Comorbidity burden was identified with the Romano version of the Charlson Comorbidity Index (CCI). TIE NDMM patients were characterized by demographic and clinical characteristics, first-line regimens, and overlap in age, comorbidity burden, and frailty. Standardized mean differences (SMD) in proportions were calculated to determine if specific age, comorbidity, or frailty groups were more likely to receive the most common treatment regimens, with an |SMD| ≥0.1 considered a meaningful difference.
Results: We identified 9,677 patients in HV and 5,256 patients in Optum with TIE NDMM since 2019. Optum patients were older (86% vs. 41% aged >65) and had a higher comorbidity burden (64% vs. 58% with CCI ≥3) than patients in HV. More than a quarter of patients (31.6% in HV and 28.7% in Optum) were classified with any frailty, which included patients who are fit frail, frail, and severely frail. Frailty data had higher missingness in Optum due to missing race (9.9% vs. 26.0%). The most common first-line regimens used by patients with TIE NDMM were bortezomib, lenalidomide, and dexamethasone (VRd) (25.9% HV and 26.5% Optum), Vd (11.1% HV and 11.7% Optum), and Rd (10.0% HV and 11.6% Optum). Additional common regimens were daratumumab plus VRd (DVRd) (9.6% HV and 6.9% Optum) and DRd (3.8% HV and 9.3% Optum). In both databases, patients receiving Vd were more likely to be aged >65 and have a higher CCI than those receiving Rd. Additionally, both databases indicated that patients aged >65 and those with higher frailty, particularly severe frailty, were more likely to receive Rd vs VRd. Patients receiving Vd vs. VRd were more likely to be aged >65, have a higher CCI, and have higher frailty, particularly severe frailty in both databases. Patients aged >65 were much more likely to receive VRd vs DVRd in both databases, with higher receipt of VRd also observed in those with a CCI≥2 and any frailty.Conclusions: In insured US populations, Vd, Rd, VRd, DVd, DRd, and DVRd accounted for 60 to 66% of first-line treatments received by patients with TIE NDMM since 2019. Severely frail patients tended to be prescribed doublet vs triplet regimens, while those with any frailty were channeled into triplet regimens vs quadruplet regimens. Patients with high comorbidity burden were more likely to be channeled away from regimens with lenalidomide, likely due to the safety profile. Older patients generally received doublets over triplets and triplets over quadruplets, likely due to the higher prevalence of comorbidity and frailty in this population. Limitations of this study include potential bias from algorithms and incomplete capture of TIE status. For standard of care comparators in trials including frail TIE NDMM patients, Vd or Rd may be suitable for severely frail patients, while VRd may be a better comparison for trials including fit frail patients. For highly comorbid patients, an appropriate comparator might be VRd instead of DVRd, depending on lenalidomide tolerance.
