Potential Pitfalls of Serum Free Light Chain Analysis to Assess Treatment Response for Multiple Myeloma

Abstract

Listen

Translate article

BackgroundThe serum free light chain (FLC test) allows measurement of low concentrations of FLC. Post-transplantation, especially after tandem autologous transplants and consolidation therapy, the immune system is often extremely suppressed and its recovery is disorganized.Patients and MethodsThis study was limited to patients with multiple myeloma, plasma cell leukemia and amyloidosis, who received autologous transplantation and consolidation therapy at the University of Iowa Hospitals and clinics. Most of these patients had already received some form of induction therapy with IMIDs or proteasome inhibitors or in combination. They then proceeded with a cycle of D-PACE followed by one or two autologous transplants. The preparative regimen for virtually all patients was VDT-MEL. Post-transplantation, most of the patients received consolidation therapy with VTD the first year and either VCD or Revlimid/dexamethasone for second year. Thereafter, all myeloma therapy was halted. Serum free light chains were measured with polyclonal FLC antisera according to Freelite, Binding site, UK. The kappa/ lambda ratio was calculated.ResultsIn total 142 patients were evaluated; 12 % (17/142) of patients were found to have abnormal light chains ratio but no other evidence of active disease, including negative serum M-protein, serum IFE, urine M-protein and urine IFE. In addition, bone marrows showed no evidence of clonal plasma cells by both 10-color flow cytometry and FISH analysis of CD138 selected plasma cells; both methods have a sensitivity of ≥ 10-4. The κ/λ ratio was abnormal due to increase/decrease in the same light chain as the M- protein in 11/17 patients; 6/17 patients had abnormal κ/λ ratio due to increase in the opposite light chain as the M- protein (Table 1)Table 1Patient with abnormal light chains due changes in Involved light chain levelsAgeGenderM protein/Light chainTransplantM proteinAbnormal light chainImmunofixationElevated or decreasedDuration of abnormal ratio64MaleIgG KappaTandem0.0KappaNegativeElevated2 weeks58FemaleIgA KappaTandem0.0KappaNegativeElevated4 weeks46FemaleKappaTandem0.0KappaNegativeElevated4 weeks58MaleIgG KappaTandem0.0KappaNegativeElevated20 weeks55MaleIgG KappaTandem0.0KappaNegativeElevated4 weeks60MaleIgG KappaTandem0.0KappaNegativeElevatedOne week60FemaleIgA KappaSingle0.0KappaNegativeElevated8 weeks68FemaleIgG KappaSingle0.0KappaNegativeElevated26 weeks42MalekappaTandem0.0KappaNegativeElevatedOne week67MaleKappaSingle0.0KappaNegativeDecreased3 weeks68MaleIgG KappaSingle0.0KappaNegativeElevated8 weeksPatient with abnormal light chain ratio due to changes in the opposite light chain levels53FemaleIgG LambdaTandem0.0KappaNegativeElevated2 weeks62FemaleIgA lambdaTandem0.0KappaNegativeElevated6 weeks50MaleLambdaSingle0.0KappaNegativeElevatedOne week60MaleIgG LambdaTandem0.0KappaNegativeElevated100 weeks68FemaleIgA LambdaSingle0.0KappaNegativeElevated8 weeks68MalelambdaSingle0.0KappaNegativeElevated4 weeksConclusions According to the IMWG uniform response criteria, patients achieving CR for whom the involved FLC reduced sufficiently to normalize the FLC ratio (range, 0.26 to 1.65) in the absence of monoclonal BMPCs as assessed by immunohistochemistry or immunofluorescence are considered to have achieved stringent CR. However, patients can be in stringent complete remission with abnormal k/l ratios if 1) the ratio is abnormal because the non-involved free light chain is elevated while the involved free light chain is normal; 2) the ratio is abnormal because involved light chain is elevated, with no other evidence of disease, including multicolor flow cytometry and FISH analysis on selected plasma cells of the bone marrow and imaging by MRI and/or PET-CT scan. This occurred in > 10% of patients. It should be noted that the FLC causing the abnormal k/l ratio was always kappa. The IMWG criteria should be adjusted these potential pitfalls. DisclosuresNo relevant conflicts of interest to declare.