Predictors of early response to initial therapy in patients with newly diagnosed symptomatic multiple myeloma

Response to therapy in newly diagnosed symptomatic multiple myeloma (NDMM) can impact long-term outcomes. It is not clear if baseline laboratory parameters can predict an early, deep response. Totally 1,304 patients with NDMM seen between 2001 and 2013 at Mayo Clinic Rochester were studied. The association between baseline laboratory parameters and early, deep response defined as a very good partial response or better (VGPR+) within four cycles of treatment was investigated. Multivariable logistic regression was used to assess the associations between the parameters of interest and response. Multivariable proportional hazards regression was used to assess the association between response and overall survival. In the entire cohort, greater absolute free light chain (FLC) differences (OR 2.38, 95% CI 1.48-3.82), younger age (OR 2.18, 95% CI 1.28-3.71), lower hemoglobin (OR 1.68, 95% CI 1.12-2.54), and IgA myeloma (OR 1.66, 95% CI 1.10-2.51) were associated with increased odds of achieving VGPR+ after four cycles. Among patients receiving novel agents in general and immunomodulators in particular, these effects were more pronounced. In patients receiving proteasome-inhibitors, higher creatinine (OR 3.83, 95% CI 1.37-10.1), lower calcium (OR 3.37, 95% CI 1.36-8.35), and greater absolute FLC differences (OR 2.50, 95% CI 1.10-5.71) were associated with better response. In a landmark analysis at 4 months from diagnosis, achieving VGPR+ was associated with decreased risk of subsequent mortality (HR 0.69, 95% CI 0.53-0.86). In summary, several parameters were associated with an early, deep response to treatment, revealing distinct sets of predictors for immunomodulator- and proteasome-inhibitor-containing regimens. Achieving VGPR+ after four cycles translated into increased overall survival.