Time to plateau as a predictor of survival in newly diagnosed multiple myeloma

Response rates in newly diagnosed multiple myeloma have improved dramatically with the introduction of highly effective novel therapies. However, survival in patients achieving optimal responses to initial treatment can vary significantly, and new prognostic indicators are required to improve risk stratification. We investigated the relationship between time to plateau (T_Plat ) and survival in 1099 newly diagnosed patients treated with novel agents at our institution from 2005 to 2015. T_Plat was defined as time from initiation of first-line therapy to best response to first-line therapy. The median T_Plat was 4.9 months (0.7-58.6) and plateau duration was 1.8 years (0.2-11.0). Patients who required > 120 days to achieve a plateau had longer modified overall survival (mOS) and progression free survival (mPFS) calculated from a landmark of best response (P < .001 for both comparisons). Statistically significant improvement in mOS was retained in subgroup analysis based on age and whether patients received upfront autologous hematopoietic stem cell transplantation (ASCT) (P < .001 for all comparisons). Our results suggest that patients who respond more gradually to initial therapy (T_Plat  > 120 days) experience longer survival compared to more rapid responders. Patients with a prolonged T_Plat could represent an "ongoing responder" phenotype that portends a survival advantage independent of treatment with upfront ASCT, depth of response, and biologic markers such as ISS stage and cytogenetic risk.