The Serum Free Light Chain Assay Allows Earlier Detection of Relapse/Progression of Multiple Myeloma After Autologous Hematopoietic Cell Transplantation
Authors: Wirk Baldeep 
Published: October 2019

Abstract 4466
The International Myeloma Working Group (IMWG) guidelines use serum free light chain (SFLC) response criteria only in multiple myeloma (MM) patients without measurable M-protein in serum or urine and to satisfy stringent complete remission (sCR) criteria. Current response criteria use changes in intact immunoglobulin measured by serum protein electrophoresis and immunofixation (SIF). The role of the SFLC assay during follow up of MM patients with measurable intact immunoglobulin after autologous hematopoietic cell transplantation (auto-HCT) is not well defined. In order to assess the role of the SFLC assay (Freelite; The Binding Site Group Ltd, Birmingham, UK) during the follow up of MM patients (with measurable M protein in serum or urine), and its role in detecting relapse compared to SIF test, a retrospective analysis of 20 MM patients after melphalan 200 mg/m2 conditioned first auto-HCT was conducted. Patients were followed for a median 15 months (range 3–36 months) between 2008 and 2011. Each patient had both the SFLC assay and SIF performed every 3 months at each routine clinic visit. No patient had renal failure (defined as serum creatinine 2 mg/dl or more). No patient deaths occurred during the follow up period. Two groups were identified. 10 patients without relapse had the following characteristics: median age at HCT 55 years (range 46–68 years); median time from diagnosis to auto-HCT 6.5 months (3–18 months); Durie-Salmon stage IIIA (n=7), stage IA (n=3); IgG kappa (n=5), IgG lambda (n=5); response to HCT very good partial remission VGPR 1 (n=5), CR1 (n=3), and sCR1 (n=2). All patients without relapse maintained a normal SFLC ratio (0.26–1.65) after HCT with negative SIF (n=5), or stable SIF (n=3) and in 2 patients (who were on lenalidomide maintenance), the SIF became negative 12 months and 18 months after HCT. 10 MM patients relapsed after auto-HCT: median age at HCT 55 years (range 46–68 yrs); Durie-Salmon stage IIIA (n=9), IA (n=1); IgG kappa (n=4), IgG lambda (n=2), kappa (n=2), lambda (n=1), IgA kappa (n=1); median time from diagnosis to HCT 8 months (range 4–28 months); response to HCT VGPR1 (n=7), CR1 (n=3). In all the patients who relapsed, the SFLC ratio became abnormal (<0.26 or >1.65) at a median of 3 months (range 3–12 months) before any other test detected relapse, (including SIF, bone marrow biopsy) and the SFLC ratio remained abnormal and continued to worsen over the follow up period. Salvage chemotherapy was begun at a median of 3 months (range 3–12 months) after the SFLC ratio became abnormal after confirmation of relapse by current approved methods (elevation of SIF or bone marrow biopsy). In follow up after HCT, 5 patients who relapsed developed an abnormal SFLC ratio (<0.26 or >1.65) without a concomitant increase in SIF and these patients had bone marrow biopsy confirmation of relapse (25% increase of plasma cells from baseline). In one patient, the SFLC ratio became abnormal at 3 months post HCT with negative SIF, and negative bone marrow biopsy at 3 months after HCT and multiple extramedullary plasmacytomas were found at 4 months after HCT accounting for the relapse.

Conclusion:
Abnormal SFLC ratio allowed earlier detection of relapse/progression of MM after auto-HCT even in those with measurable M protein in serum and urine and not only in light chain MM but also in those with intact heavy chain immunoglobulins compared to SIF and this can be critical for earlier intervention with salvage strategies. There are currently no guidelines for use of the SFLC assay in follow up of MM patients with measurable serum and urine M protein. The serum free light chain assay should be used concomitantly with serum protein electrophoresis and immunofixation in the follow up of MM patients after auto-HCT.

Disclosures:
No relevant conflicts of interest to declare.