Background. Protein electrophoresis and immunofixation in the serum (SPEP - SIF) and urine (UPEP – UIF) have been routinely used for decades for characterizing and quantifying the M protein in Multiple Myeloma (MM). However, these techniques are notoriously tarnished with inaccuracy, despite improvements in recent years. The most important breakthrough in the field in recent years was the discovery of the Serum Free Light Chain Assay (sFLC), a routine quantitative and automated assay that measures kappa and lambda sFLC, however this was added to / rather than replaced traditional tests in the diagnostic armamentarium of MM. Recently, a new test quantifying paired clonal and non-clonal immunoglobulins (heavy/light chains HLC i.e. IgGκ/IgGλ) in serum was developed. Here we aim to assess the new HLC assays as tools to replace SPEP / IFE during MM patient monitoringMaterials and methods. 110 Myeloma treated with pomalidomide and dexamethasone in two IFM studies (IFM 2009-02 in end stage RRMM and IFM 2010-02 in del17p and t(4;14) RRMM ) were included. The criteria for selection were that patients had measurable intact immunoglobulin myeloma according to IMWG criteria (M spike ≥10g/L), using serum and/or urine protein electrophoresis, with exclusion of patients solely measurable on UPEP and sFLC. All sera were collected centrally before initiation of treatment and sequentially every cycle until progression. Hevylite® (HLC) was measured in the biology laboratory of CHRU of Lille, France and results compared to traditional measurements. Along with SPEP, SIF, UPEP, UIF, and sFLC, we have also measured IgA HLC (IgA k and IgA l) and IgG (IgG k and IgG l) and the corresponding difference (clonal - non clonal) and ratio (clonal/non clonal).Results. Overall, 80% were measurable on SPEP with a median serum level of 31g/L (CI95% 19;42), and the remaining also had UPEP measurable myeloma with a median serum level of 0.66g/24h (CI95% 0.4;1.3). The median involved HLC level was 29.7g/L (CI95% 17.6;43.3), the median involved HLC difference clonal - non clonal was 28.8g/L (CI95% 15.6;42.7), the median involved HLC ratio clonal / non clonal was 51.9 (CI95% 18.3;203.9).Since all patients had a measurable intact immunoglobulin-based disease according to IMWG criteria, we have first confirmed that patients had also a measurable disease by HLC. All patients had an abnormal HLC ratio but one patient, who was measurable with an abnormal IgG L involved HLC test. Approximately 32% of patients had an M-spike below 20g/L and/or an electrophoretic migration in beta region meaning in the range of lack of sensitivity of the techniques used, all of whom had a measurable disease using involved HLC level and/or a measurable HLC ratio.We then sought to study the response rate according to HLC, and for that purpose we applied the exact same criteria as to the sFLC-based response criteria recommended by IMWG (e.g. normal ratio is CR and if abnormal ratio, then <50% reduction in the difference clonal – non clonal is SD, ≥50% - <90% reduction is PR, >90% reduction is VGPR). The ORR in the 2 studies as a whole using traditional measurements was 32%, including 29% PR rate, absence of CR, and 44% had SD (SD and MR). Using HLC, the ORR was 36%, including 26% PR rate and 4.0% CR, and 33% had SD (r² 0.823, p<.0001). Interestingly, 7 patients classified as SD with regular techniques, were progressive disease using HLC, anticipating a progression of Myeloma. Similarly, 5 patients classified as SD with regular techniques, were ≥PR using HLC.Conclusion. HLC is a new routine quantitative and automated assay that measures Immunoglobulin heavy chain/light chain pairs immunoassay, allowing diagnosis, prognosis and precise assessment of the response to treatment and disease progression in all cases with Myeloma treated with pomalidomide and dexamethasone in 2 different clinical trials. Our study indicates that HLC may be used as a replacement for traditional tests and may offer greater sensitivity in some instances. Furthermore, obviating the need for interpretation may standardize assessments of patients during trials. Future studies might confirm this data analysis in larger trials. DisclosuresKarlin:Janssen: Honoraria; celgene: Consultancy, Honoraria; Sandoz: Consultancy. Hulin:Celgene: Honoraria. Stoppa:Celgene Jansen: Honoraria. Marit:Celgene, Janssen: Congress expenses Other.