OBJECTIVES: Daratumumab in combination with lenalidomide and dexamethasone (DRd) is indicated for patients with newly diagnosed transplant-ineligible multiple myeloma. Previous hazard ratio network meta-analyses (NMA) have shown DRd to be clinically superior to other treatments. Proportional hazard assumption (PHA) violations in the network, however, required the exploration of advanced NMA methods. This research aimed to conduct a parametric NMA (PNMA) to evaluate overall survival (OS) and progression-free survival (PFS) for DRd compared with relevant treatments in the United Kingdom (UK) setting.

METHODS: Data on DRd and relevant UK comparators (lenalidomide[continuous]-dexamethasone [Rdc], melphalan-prednisone-thalidomide [MPT], bortezomib-melphalan-prednisone [VMP]) were identified through a systematic literature review. Pseudo-individual patient-level data were obtained by using the Guyot algorithm to reconstruct data from digitized published Kaplan-Meier curves. The PNMA distributions included Weibull, exponential, log-normal, Gompertz, log-logistic, gamma, and generalized gamma. The models were compared based on leave-one-out information criteria and mean survival (95% confidence interval [CI]). MAIA (DRd) was used as the reference trial.

RESULTS: The evidence network consisted of six and seven trials for OS and PFS, respectively (MAIA, FIRST, VISTA, IFM99-06, IFM01/01, Sacchi 2011, TMSG [PFS only]). The PHA was violated in one (PFS) and two (OS) trials. The gamma (PFS) and Gompertz (OS) distributions showed the best statistical fit. Treatment with DRd resulted in the longest OS at 11.6 years (95% CI: 7.2, 36.1), followed by Rdc (5.7 [4.9, 7.0]), MPT (4.9 [4.0, 6.3]), and VMP (4.4 [3.3, 6.3]). DRd also showed the longest PFS (8.0 years [6.7, 9.8]), followed by Rdc (4.0 [3.5, 4.7]), VMP (2.7 [1.8, 4.0]), and MPT (2.6 [2.1, 3.2]). These results aligned with previously published indirect treatment comparisons.

CONCLUSIONS: PNMA was considered an appropriate method to address PHA violations in the network. The method confirmed the hazard ratio NMA results that demonstrated DRd improves survival compared with other treatments.