PS1418 POMALIDOMIDE-BASED TREATMENT IN RELAPSED REFRACTORY MULTIPLE MYELOMA: ANALYSIS OF BASELINE CHARACTERISTICS AND SAFETY PROFILE OF PATIENTS WHO DIED IN THE EUROPEAN POST APPROVAL SAFETY STUDY
Authors: B. Gamberi, N. Abildgaard, A. Ramirez Payer, C. Kyriakou, M. Schmidt Hieber, F. Di Raimondo, E. Kueenburg, A. Di Micco, B. Rosettani, M. Atiba-Davies, P. Bacon, T. Plesner
Journal: HemaSphere (2019)

Background: Monoclonal gammopathy of clinical significance(MGCS) is defined by the relationship between a small dangerous B-cell clone and severe organ damage due to the toxicity of the monoclonal immunoglobulin(MIg) or its fragment and their deposition in different organs. The kidney is one of the main targets of the MGCS which may occur in all B cell or plasma cell proliferative disorders that produce a nephrotoxic monoclonal immunoglobulin(MIg). The treatment strategy is based on chemotherapy adapted to the nature of the underlying clone. The rapid suppression of the secretion of nephrotoxic MIg has been shown to impact patient survival and increase the patients’ quality of life. Aims: In our study we evaluated the impact of kidney damage on patient's survival. Methods: Our cohort included 151 consecutive patients with MGCS-associated organ damage since 2004 to 2019. The most common involved organs were kidney, heart, liver, nerves system and gastrointestinal tract. The diagnosis in most cases was established by organ biopsy, serum and urine protein immunofixation, analyses of serum free light chains, bone marrow aspiration and biopsy with flow cytometry. MGCS- associated renal lesions were: AL amyloidosis 88% (n = 126), monoclonal immunoglobulin deposition disease (MIDD) 5,6%(n = 8),proliferative glomerulonephritis with monoclonal Ig deposits and C3 glomerulopathy 4,2%(n = 6), trombotic microangiopathy 1,4 %(n = 2) and cryoglobulinemic glomerulonephritis type 1 0,7%(n = 1). Results: Median age of the patients was 62 years (38–79). Median follow-up was 24,2 months (1–117,5 months). Renal involvement(RI) was noted in 92% of patients (n = 142). 21,8% (n = 31) of these patients required dialysis. The median time to dialysis was 2 months (1–70months).71,1% (101 patients) had nephrotic syndrome at the time of diagnosis. Prognostic criteria for RI were assessable in 117 patients. These criteria included a reduction in eGFR<50 ml/min/1.73m2 and proteinuria (PU)>5 g/24 hours. In our cohort, patients with stage I were 16,1% (n = 21), stage II – 46,4% (n = 66), stage III-30,2%(n = 43). The 5-years rate of progression to dialysis was significantly higher in patients with stage III (46,5% vs 9,1% vs 0 %, p < 0,0001, for stage III, II, I,respectively) and in patients with nephrotic syndrome (23,8% vs 3,6%,p = 0,0026,for nephrotic syndrome and asymptomatic proteinuria). Stage III of RI was independent predictor of poor overall survival (OS), but did not impact on renal progression-free survival (PFS). 5-years overall survival was: 61,9%, 71,2 and 51,2% (p = 0.0052), 5-years renal PFS was 90%, 67,7% and 60 % (p = 0,35) for I,II,III renal stage,respectively. Treatments included chemotherapy in 73% (n = 106) and stem cell transplantation 12,5% (n = 18). The median time from treatment initiation to first and best renal response was 7 month (1–68months) and 13,5month (1–69months) respectively. We assessed renal response in 61 patients. In our group of patients, the complete renal response (CR) was achieved in 4,9% cases (n = 3), very good partial response (VGPR) – 42,6% (n = 26), partial response – 32,7% (n = 20). 19,6% (n = 12) have not achieved renal response (NR). OS in patients with CR was 100%, VGPR–88,4%, PR–95%, NR–58,3% (p = 0,0031).5-years renal PFS in patients who achieved renal response was 70,9%. Summary/Conclusion: Renal involvement and the depth of the response is a prognostically significant factor and a predictor of overall survival and renal survival of patients with MGCS. There is a need for early diagnosis of renal involvement, in order to identify and treat these patients before irreversible organ damage occurs.