Predictors of frontline doublet or triplet regimen initiation in transplant-ineligible newly diagnosed multiple myeloma

Aims: To identify predictors for initiation of frontline doublet versus triplet therapy for transplant-ineligible newly diagnosed multiple myeloma. Materials and methods: Using Flatiron Health data, a random forest model was used to identify baseline predictors of frontline doublet or triplet use. Results: The random forest model had good predictive power, with 74% probability of successfully predicting the regimen received (doublets or triplets) for a given patient. Regression analyses found that patients treated with doublets were more likely to be older (age >= 80 versus <60 years: odds ratio [OR] = 0.15, P < 0.001) and frail (frail versus fit: OR = 0.73, P = 0.023). Predictors of triplet regimen use included Black race (Black versus white: OR = 1.31, P = 0.025), urban state (urban versus rural: OR = 1.38, P = 0.042), >= 1 form of trisomy (OR = 1.39, P < 0.001), del(17/17p) (OR = 1.87, P < 0.001), detectable M protein (OR = 1.33, P < 0.001), higher disease stage per International Staging System (stage 2 versus 1: OR = 1.42, P = 0.001; stage 3 versus 1: OR = 1.35, P = 0.005), and >= 1 diagnosis for musculoskeletal and connective tissue diseases (OR = 1.45, P = 0.002). Triplet regimen use increased in recent years. Conclusions: While frontline triplet therapies have shown improved efficacy over doublets with tolerable safety, doublet use remains in older and frail patients, creating an opportunity to improve outcomes in this particular patient population.