Serum Free Light Chain Analysis Improves Monitoring of Multiple Myeloma Patients Receiving First-Line Therapy with the Combination of Velcade, Doxil, and Dexamethasone (VDD).
Authors: Lebovic Daniel , Kendall Tara , Brozo Christine , McAllister Amanda , Hari Malathi , Alvi Sairah , Robson Ewan J.D. , Jakubowiak Andrzej J. 
Published: October 2019

Abstract
Introduction: Serum free light chains (sFLC) have a short 2–6hr serum half-life compared with up to 3 weeks for intact immunoglobulins (Ig). sFLC analysis (Freelite™, The Binding Site Inc) therefore provides earlier therapeutic information for Intact Ig Multiple Myeloma (IIMM) patients producing monoclonal FLC. Also, it may be a more sensitive method than urinary Bence Jones protein (BJP) analysis for monitoring light chain MM (LCMM) patients. We assessed the benefits of monitoring sFLC in addition to serum and urine M-protein in previously untreated MM patients receiving combination therapy with Velcade, Doxil, and Dexamethasone (VDD).
Methods: 38/40 patients enrolled in a Phase II clinical trial received up to six 3-week VDD cycles (Velcade: 1.3 mg/m2IV; Days 1, 4, 8, 11, Doxil: 30 mg/m2 IV; Day 4, and Dexamethasone: 20 mg PO; Days 1, 2, 4, 5, 8, 9, 11, 12. During the first cycle, Dexamethasone was given at 40 mg per dose, with the first 10 patients receiving Dexamethasone at 40 mg PO on Days 1 – 4). Responses were determined based on uniform response criteria (URC, Durie et al. (2006) Leukemia20, 1467). 31/38 patients had IIMM (16 IgGκ, 8 IgGλ, 5 IgAκ, 2 IgAλ). 7/38 patients had LCMM (3 κFLC, 4 λFLC). 8/31 IIMM and 2/7 LCMM patients had sFLC levels <10mg/dL at baseline, too low to define measurable disease according to the URC.
Results: sFLC and intact Ig response was similar in 16/31 IIMM patients (at least partial response (PR), 4/16 had baseline sFLC levels <10mg/dL). In 7/31, the difference between involved and uninvolved sFLC levels fell to <50% of baseline one cycle or more earlier than intact Ig levels indicated at least PR (for 3/7, intact Ig levels indicated stable disease). In 1 patient, intact Ig levels fell to <50% of baseline before sFLC. 2/31 patients displayed probable light chain escape during treatment, with a third patient’s disease progression indicated earlier by sFLC than intact Ig. In 4/31 patients, sFLC analysis provided no useful information. sFLC ratios normalised in 6/31 IIMM patients, supportive of a stringent complete response. 16/31 IIMM patients had no significant BJP; in 15/31 with BJP, changes in sFLC and BJP levels were similar. Changes in sFLC and BJP levels agreed in 5/7 LCMM patients. 2/7 became negative for BJP while continuing abnormal sFLC levels suggested residual disease (in both these patients, baseline sFLC levels were <10mg/dL).
Conclusion: Analysing sFLC in addition to intact Ig generated clinically relevant detail in 10/31 (32%) IIMM patients, with earlier response identified in 7 patients and probable disease progression in 3 patients. sFLC analysis provided a more sensitive means of monitoring response to therapy and identifying residual disease in 2/7 (29%) LCMM patients. No clinical information would have been lost by replacing BJP with sFLC analysis when monitoring either IIMM or LCMM. Our data suggests that the URC 10mg/dL baseline sFLC cut-off may not always be appropriate, as sFLC analysis of some patients with <10mg/dL was informative. Furthermore, sFLC analysis can be used in assessing stringent complete response. This analysis of data from a controlled clinical trial shows that sFLC can be used not only as a useful tool to monitor initial therapy of multiple myeloma, but also as a possible replacement for 24-hr BJP analysis.