PB2189 FREE LIGHT CHAINS IN MULTIPLE MYELOMA: IS IT TIME TO EXTEND THEIR APPLICATION?
Authors: U. Markovic, V. Leotta, R. Giubbolini, A. Romano, V. Del Fabro, F. Di Raimondo, C. Conticello
Journal: HemaSphere (2019)

Background: Free Light Chain (FLC) assay is used for multiple myeloma screening, prediction of risk progression and response assessment as indicated by IMWG guidelines, particularly to define stringent complete response (sCR). The assay is also recommended in cases of unmeasurable (non‐secretory, NS) or low values of M‐protein (oligo‐secretory, OS). Aims: Here we describe the value of FLC assay in predicting extramedullary relapse in four MM patients. Methods During the course of therapy, FLC was monitored routinely on a monthly basis. Results: An OS MM IgG κ patient ( first case ) started in May 2017 4 th line KRd therapy, due to new lytic lesions, with negative BM biopsy. During the course of therapy, sIFE remained negative, while sFLC continued to rise (May 2017–March 2018: sFLC κ 175 vs 340 mg/L, rFLC 4.2 vs 19.9). In March 2018 a right femur mass appeared and histology, confirmed EMD relapse. Patient underwent surgical removal and rFLC returned within normal range (1.3). Considering that it was the only site of disease, KRD regimen was restarted in June 2018 for four more cycles. Unfortunately, in November 2018 the knee mass reappeared, and, once again, sFLC was altered (FLC κ 124 mg/L, ratio 25), with negative sIFE. Biopsy of the mass confirmed EMD relapse, BM biopsy remained negative. A patient with IgG κ MM ( second case ) started in May 2017 2 nd line KRd therapy for disease progression, confirmed by BM biopsy. A partial response was obtained quickly, but since March 2018 a progressive rise of rFLC was noticed (March–September 2018: rFLC 0.67 vs 1.67), and it anticipated of 5 months the increase of MP (August 2018). In June 2018 patient complained vague gastrointestinal symptoms and in September a CT scan revealed hepatic nodularities, confirmed by biopsy as hepatic EMD. A LC MM λ patient ( third case ) started in March 2017 KRd as 2 nd line treatment for disease progression (MP 0.7 g/dL, sFLC λ 2000 mg/dL, rFLC 171), with positive BM biopsy. Patient obtained CR after the first cycle, but during the treatment in June 2018 sFLC started increasing and in July alteration of liver and bilirubin tests was noticed, without any clinical sign, always with negative sIFE. In October 2018 sIFE became positive and in November MP reappeared (0.37 g/dL) while both the sFLC (June–November 2018: sFLC λ 53 vs 207 mg/dL; rFLC 6 vs 68) and the liver tests continued to rise. A solid hepatic mass was revealed and biopsy confirmed an EMD relapse. A MM IgA λ patient ( fourth case ) diagnosed with biopsy of soft paravertebral tissues, was treated with 1 st line VMP treatment in September 2018. During the treatment the patient complained sight loss and a CT scan showed the presence of a right ocular mass. The MP was reduced while sFLC increased (September–October 2018: MP 2.4 vs 0.2 g/dL; sFLC λ 158 vs 263 mg/dL; rFLC 5.7 vs 29.4). Biopsy confirmed an aggressive EMD relapse and the patient started 2 nd line KRD treatment in October 2018. A complete remission was obtained with ocular mass regression, negative sIFE and improvement of FLC. Unfortunately, in January 2019 during the fourth cycle, a cutaneous lesion appeared on the right tibia, confirmed as EMD relapse. While both the sIFE and BM biopsy remained negative, a slight increase of sFLC was noticed, although always within range. Summary/Conclusion: In all four cases an increase of FLC always preceded the diagnosis of EMD relapse irrespective of MP measurement. We therefore recommend serial use of sFLC assay, particularly in heavily pretreated patients for early detection of aggressive and/or EMD relapse.