Serum free light chain kinetics is predictive of renal response in myeloma patients with renal impairment– an ALLG trial of carfilzomib-dexamethasone therapy in frontline and relapse.

Background and Purpose Renal impairment (RI) confers adverse prognosis in myeloma; its reversal and avoidance of dialysis are crucial. We investigated whether serum free light chain (SFLC) measurements can predict renal outcome, to enable change in therapy to optimise prognosis and avoid dialysis. Patients and Methods We investigated 36 myeloma patients (17 newly diagnosed (ND); 19 relapsed refractory (RR); with median of 5 prior lines) with eGFR 15-40 ml/min treated with carfilzomib (Cfz)-dexamethasone to determine whether SFLC kinetics can predict renal outcomes, and assess efficacy and tolerability. Results The change in involved SFLC at Cycle 2 Day 1 was significantly correlated with renal function; for every one log10 reduction in involved SFLC, eGFR increased by 9.0 - 15.0 mL/min at cycles 2-4, with SFLC reduction of 54-78%. At a median follow-up of 30.6 months, renal outcomes were favorable - CRrenal 25%, MRrenal 36%. Disease responses (ND 100%, RR 75%), progression-free survival (ND 32.2 months, RR 11.1 months) and overall survival (ND not reached, RR 42.0 months) were comparable to patients without RI. There was significant toxicity, including Cfz-related cardiac impairment of 20% within a cohort with high co-morbidity, and a high incidence of infections. Conclusion We propose that one log10 reduction in involved SFLC at Cycle 2 Day 1 is an appropriate target for reducing the risk of dialysis in myeloma patients with RI; below this threshold patients may benefit from a change in therapy. While Cfz-dexamethasone achieved favorable renal and disease outcomes, toxicity can be significant in this vulnerable cohort. Microabstract The utility of serum free light chain measurements (SFLC) to predict renal outcome, to optimise prognosis and avoid dialysis, was investigated in myeloma patients with renal impairment treated with carfilzomib-dexamethasone. We found a significant correlation between the change in involved SFLC at Cycle 2 with renal function, from which a threshold to change therapy is proposed to avoid suboptimal outcome. Disease response and survival were favorable but there was significant toxicity including cardiac impairment and infections.