Day 21 serum Free Light Chain (FLC) levels as a predictor of response to therapy in symptomatic multiple myeloma

Introduction: Serum Free Light Chain (sFLC) assay has a major role in the screening, diagnosis and monitoring in patients with Multiple Myeloma (MM). Measuring involved Free Light Chain (iFLC) has a proven advantage due to the short half-life compared to that of M-protein, thus useful as a prognostic tool for the assessment of response to therapy. It is established that achieving VGPR (very good partial response) or better after induction chemotherapy is associated with better OS (overall survival) and PFS (progression free survival) in myeloma patients. Few studies have shown that early reduction in iFLC during treatment is associated with achievement of VGPR or better. Objective: To study the predictive value of reduction of involved free light chain level on Day 21 of chemotherapy for achievement of VGPR after 4 cycles of induction chemotherapy. Methods: We conducted a prospective observational study in twenty eight patients of newly diagnosed Multiple Myeloma with iFLC ≥ 100mg/L. Serum FLC assay was done at baseline and on day 21 of therapy. All patients were followed up till the end of induction therapy for response assessment based on the IMWG criteria. Receiver Operator Characteristic (ROC) curve analysis was done to determine the cut off value of percent reduction in day 21 iFLC for achievement of VGPR or better. Results: After the induction chemotherapy, out of 28 patients, 13 patients achieved CR, 8 patients achieved VGPR, 4 patients achieved PR and 2 patients had stable disease (≥ VGPR = 21 patients, < VGPR = 6 patients). One patient expired after 2nd cycle of chemotherapy. The mean per cent reduction in day 21 iFLC level as compared to baseline was 91.5% and 57.1% in patients achieving ≥ VGPR and < VGPR (P < 0.0001), respectively. No other baseline parameter was found to be significantly different between the 2 groups. ROC curve analysis demonstrated a cut off of 84% reduction in iFLC value on day 21 (AUC of 0.937) had a sensitivity of 85.7% and a specificity of 100% in predicting the achievement of VGPR after four cycles of induction chemotherapy. Conclusion: Monitoring iFLC levels on Day 21 can be used as an important tool for early identification of responders/non responders to myeloma therapy. We recommend serum FLC assay to be done on day 21 as a real time assessment of treatment response in newly diagnosed myeloma patients. Key words- Multiple Myeloma, involved Free Light Chain (iFLC), Very Good Partial Response (VGPR)