Prognostic Impact of the Hevylite Assay in Patients With <scp>IgG</scp> or <scp>IgA</scp> Multiple Myeloma Treated Within the <scp>GMMG</scp> ‐ <scp>MM5</scp> Trial

Response assessment during treatment of multiple myeloma (MM) typically relies on immunofixation and serum electrophoresis. However, low levels of IgG and especially IgA paraprotein are difficult to quantify reliably. The Hevylite Assay quantifies the kappa and lambda fractions of IgG and IgA separately and is useful to determine response to therapy. Using serum samples of 360 evaluable patients from the prospective GMMG-MM5 trial (EudraCT-No. 2010-019173-16) we assessed the normalization of the kappa/lambda ratio with the Hevylite Assay (HLCr) at baseline, after induction, mobilization, autologous blood stem cell transplantation, consolidation and every three months during maintenance or follow-up within two years after the end of consolidation. We observed a steady increase in the proportion of patients with normalized HLCr over the course of therapyAchieving HLCr normalization any time until the end of consolidation was associated with a trend towards a prolonged progression-free survival (PFS; hazard ratio (HR) = 0.75, 95% confidence interval (95% CI) = 0.56-1.01, p = 0.06) but not overall survival (OS; HR = 0.94, 95% CI = 0.69-1.26, p = 0.66) in multivariable time-dependent Cox regression analyses. Using a landmark analysis from the end of consolidation there was again a marginally statistically significant effect of HLCr normalization by the end of consolidation on PFS using a multivariable Cox model on the subset of the two study arms with continuous lenalidomide maintenance (HR 0.61, 95% CI 0.37-1.02, p = 0.06). No such effect was observed in study arms in which maintenance was only applied to patients not in CR at the end of consolidation. In conclusion, our analysis of the Hevylite Assay in patients with IgG or IgA myeloma from the GMMG-MM5 study did not find evidence to support the general use of HLCr normalization as a response parameter for predicting PFS or OS. However, the differential effects of HLCr normalization depending on the way in which treatment was adapted to response may be of interest for future study designs on response-adapted therapy. Trial Registration: ISRCTN05622749.