Response: Top tertile SFLC reduction indeed is an independent feature of myeloma aggressiveness

We appreciate the thoughtful comments by Dr Dispenzieri concerning our observations that the one-third of patients with the steepest serum free-light chain (SFLC) reduction after induction cycles 1 and 2 had inferior event-free and overall survivals relative to those with lesser degrees of SFLC response. Dr Dispenzieri suggests that our results did not account for baseline levels and might in fact be a reflection of the fact that those with low baseline SFLC levels have lower percentage reductions and constitute a good prognosis group. While indeed greatest percentage SFLC reduction was observed among subjects with highest baseline SFLC levels, there was considerable overlap in the percentage reduction distributions among baseline SFLC tertile cohorts. We repeated the multivariate analysis suggested, excluding the 30 patients with normal baseline SFLC levels. As shown in Table 1, the results are essentially identical to those we published (Tables 4,5¹ ), with only a slight attenuation of P-values due to smaller numbers. We also wish to draw attention to Table 2 of our manuscript,¹  which shows that the overall adverse consequences of top-tertile SFLC reduction pertain, in a an attenuated fashion, also to the subset with top-tertile SFLC baseline levels. Thus, our initial expectation that marked SFLC reduction might counteract the negative consequences of high SFLC baseline levels was not supported by clinical outcome results. In fact, as we concluded in our paper, features of myeloma aggressiveness as reflected by high baseline SFLC levels, while associated with more rapid and profound tumor cell kill and higher rates of complete remission, account for rapid tumor regrowth between treatments and ensuing early relapse and disease-related death.