ALBERT

Description: Introduction:Renal impairment (RI) is a common complication in multiple myeloma (MM) with an incidence of 20-40%, due to the older age of the affected patients (pts) and the nature of the disease. Prognosis of pts with RI has improved in recent years (yrs), but remains closely associated with the recovery of renal function. There is little information on the renal response of relapsed refractory MM (RRMM) to new antimyeloma drugs within clinical practice, using standardized criteria such as glomerular filtration rate (GFR) estimated by the Cockroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) formulas.The primary objective of the study is to describe the renal response in RRMM pts with moderate (CrCl 30–50 mL/min) or severe renal impairment (RI) (CrCl 〈 30 mL/min) after initiating treatment (Tx). Secondary objectives include response rate, overall survival (OS), safety, and health resource utilization. We present results from a pre-planned, interim analysis with a data cut-off of June 15, 2014. Methods:This is a large ongoing observational, prospective, multicenter study in RRMM pts with moderate or severe RI (based on the CG formula) receiving antimyeloma Tx. The overall planned sample size is 300 pts to be followed for up to 36 months (mos) after the end of Tx. Renal and MM responses are evaluated according to the International Myeloma Working Group criteria. Renal complete response (renalCR) is defined as a sustained (for at least 2 mos) increase of baseline estimated glomerular filtration rate (eGFR) to ≥ 60 mL/min; a partial renal response (renalPR) is defined as an increase from 〈 15 to 30–59 mL/min, and a minor renal response (renalMR) from 〈 15 to 15–29 mL/min or, from 15–29 to 30–59 mL/min. Results:A total of 150 pts were included in the interim analysis, mean ± SD age was 74 ± 9 yrs, 53% were male, and 53% had moderate and 47% had severe RI. At baseline, 57% of pts were in first relapse. At diagnosis, 45% of pts had ISS stage III, 29% had ISS stage II, 9% had ISS stage I, and 17% had no ISS stage available. Main antimyeloma therapies were: lenalidomide (LEN)-based (37%), bortezomib (BORT)-based (30%), BORT + LEN based (5%), chemotherapy-based (25%) and, thalidomide-based (3%). The median follow-up was 4 mos. To date 38% of pts have discontinued Tx, 13% due to adverse events (AEs), and 29% have died. The main causes of death were: disease progression (8.7%), infection (6.7%), respiratory failure (3.3%), kidney insufficiency (2%), fractures (2%). The mean baseline CG/MDRD was 39.7/42.2 (± 6.3/10.2) mL/min in the moderate RI subgroup and 20.2/19.8 (± 7.6/9.8) mL/min in pts with severe RI (correlation coefficient CG vs. MDRD: 0.93). Overall, 15.3% (n = 23; 95% confidence interval [CI] 9.5–21.1,) had a renal response according to the CG formula, i.e. renal function iimproved by at least 1 KDIGO stage; 4.7% had renalCR, 0.7% renalPR and 10% renalMR. According to the MDRD formula, the renal response was 21.3% (8.6% renalCR, 12.7% renalMR). Median time to best renal response was 1.5 (range 0.6–4.6) mos. The renal response based on CG/MDRD according to antimyeloma therapies was 10.9%/20% for LEN-based, 26.7%/31.1% for BORT-based, 0%/12.5%, for LEN + BORT-based, and 10.2%/15.4%, for chemotherapy-based therapies. 24 hour (hr) proteinuria measurement was available at baseline in 70 pts (median of 1.3 g/24 hr), 77.1% of whom had 〉 0.3g/24 hr. Of these, 4 (7.4%) achieved complete proteinuria response (〈 0.3g/24 hr) and 4 (7.4%) achieved partial response (〈 1g/24 hr) by the 4th follow-up visit. The overall myeloma response (≥ partial response) was 38.0% achieved after a median of 2.9 (1.3–5.2) mos. LEN-based myeloma response was 45.5%, BORT-based 48.9% and LEN + BORT-based 50.0%. These responses seemed to be higher than those obtained with chemotherapy-based therapies (17.6%). The median time to progression (TTP) was 4.5 mos (95% CI 4.2–7.3). TTP was 16.2 mos with LEN-based, 11.8 mos with BORT-based, not reached with LEN + BORT-based, and 8.3 mos with chemotherapy-based therapies. Overall, 52% of pts had an AE and 12% a serious related AE. Conclusions: The most commonly used Tx in clinical practice in RRMM pts with RI are LEN or BORT-based. The results of this interim analysis suggest that these Tx can improve RI in approximately 15% of cases, and are associated with a higher antimyeloma response than chemotherapy-based Tx. Disclosures Morales: Celgene: Consultancy. Ruiz Boza:Celgene : Employment, Other. Garcia:Celgene: Honoraria.

Description: Introduction:Renal impairment (RI) is a common complication of multiple myeloma (MM). Almost 20% of patients (pts) present with RI at diagnosis, while approximately 40%-50% of pts will develop RI during the course of their disease. However, there is little information on the renal response of pts with relapsed refractory MM (RRMM) receiving treatment with new drugs in clinical practice. Aims: This is an observational, prospective, multicenter study conducted in pts with RRMM and RI (defined as an estimated glomerular filtration rate [eGFR] 〈 50 mL/min) to evaluate renal response to the administered therapy in pts with moderate (creatinine clearance [CrCl] 30-50 mL/min) or severe (CrCl 〈 30 mL/min) RI. Secondary objectives include MM response rate, overall survival, safety, and health resource utilization. We present results from an interim analysis 4 mos after completion of the inclusion period (cutoff: June 13, 2016). Methods:Renal and MM responses were evaluated according to International Myeloma Working Group criteria. Both eGFR by the Cockroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulas were compared to analyze renal response. Results:Overall, 312 pts (mean ± SD age 75 ± 9 yrs, 50% male, 57% in first relapse) were included in the study; 217 (70%) had moderate and 95 (30%) had severe RI, respectively. Anti-myeloma therapies administered were lenalidomide (LEN; 35% of pts), bortezomib (BORT; 21%), different chemotherapy regimens (CT; 22%), and other non-CT treatments (22%). Median follow-up was 7 mos (range, 0-39 mos). To date, 123 pts (39%) have discontinued treatment, 12% due to adverse events (AEs), and 37% have died. The main causes of death were disease progression (8.3%) and infections (6.4%). The mean baseline eGFR according to CG and MDRD formulas was 38.7/41.7 (± 8.5/11.8) mL/min in the moderate RI subgroup and 20.3/20.1 (± 8.0/10.1) mL/min in the severe RI group, with a strong correlation (coefficient 0.91) between the CG and MDRD eGFR. Overall, 13.5% (95% CI, 9.7%-17.2%) of patients had a renal response (5.8% renal complete response [renalCR], 0.3% renal partial response [renalPR], and 7.4% renal minor response [renalMR]) according to the CG formula while responses measured by the MDRD formula, were 17.3% (9.9% renalCR, 0.3% renalPR, and 7.1% renalMR). Median time to best renal response was 1.8 mos (range, 0.5-8.9 mos). After adjusting for demographic and clinical characteristics, there were no significant differences in GFR improvement between pts receiving LEN- and BORT-based treatments (P = 0.706). Arterial hypertension and female sex were statistically significantly associated with poor renal response. The overall MM efficacy response rate (≥ PR) was 33.4%, achieved after a median of 3.4 mos (range, 0.07-37.8 mos). For pts receiving BORT and LEN, respectively, the overall response rates were 43.5% and 44.8%, whereas only 23% of pts receiving CT achieved at least PR. Progression-free survival was 13.3 mos with LEN-based, 6.8 mos with BORT-based, and 7.5 mos with CT-based therapies (P = 0.006). Conclusions: Preliminary results of this study in pts with RRMM and RI show that LEN- and BORT-based therapies are the regimens most commonly used in clinical practice in these pts. Overall, these therapies can improve RI in approximately 13% of cases, with no differences seen in renal function improvement between LEN- and BORT-based treatments. Disclosures De La Rubia: Amgen, Bristol Myers, Celgene, Janssen: Consultancy. Morales:Celgene: Consultancy. García-Muñoz:Celgene, Roche: Consultancy. Duran:Celgene: Employment.

Description: Abstract 2804 Poster Board II-780 Background: Monoclonal gammopathy of undetermined significance (MGUS) progresses to plasma cell dyscrasia, mainly multiple myeloma (MM), at a rate of approximately 1% per year. Moreover, recent studies have shown that MM is nearly always preceded by MGUS, encouraging investigators to find better predictors for MM development in order to implement strategies to prevent or delay progression. In addition, a high prevalence of MGUS has been noted in a series of patients with immune disorders or chronic infections. Multiparameter flow cytometry allows the identification and quantification of both monoclonal and polyclonal plasma cells. This study analyses the relationship between monoclonal and polyclonal bone marrow plasma cells (BMPC), studied by means of flow cytometry, and its association with either immune or infectious disorders, or the development of MM in newly diagnosed MGUS patients. Methods: We conducted a retrospective cohort study to analyse the prognostic value of the aberrant (CD38++ CD138+ CD19– CD45weak) to normal (CD38++ CD138+ CD19+ CD45+) phenotype bone marrow plasma cells ratio (A/N ratio) and another 13 variables at baseline for the development of a plasma cell dyscrasia. We also performed a cross-sectional study to evaluate the association of those variables at baseline with the presence of a chronic immune response disorder. In each patient, the following variables were examined: age, sex, hemoglobin, serum creatinine, serum calcium, B2-Microglobulin, type and size of the serum monoclonal component (MC), isotype of the MC immunoglobulin, presence of urine MC, quantification of serum immunoglobulin levels, erythrocyte sedimentation rate, BMPC percentage and presence of atypical plasma cells on light microscopy, and aberrant and normal phenotype BMPC percentages. The effect of variables on progression was calculated using a Cox proportional hazards regression model. To identify variables at baseline associated with immune or chronic infectious disorders. a series of univariate and multivariate analyses was fitted using a binary logistic regression strategy. Results: Between March 1997 and April 2008, flow cytometry analysis on bone-marrow samples was performed on 322 patients with newly diagnosed MGUS. Median patient age was 71 years (interquartile range (IQR) 63-78 years) with a slightly male predominance (51%). Median follow-up was 46 months (IQR 23-58 months). During the period of observation, in 23 (7.1%) patients a transformation was registered into: MM (n=22), and primary amyloidosis (n=1). A total of 24 (7.4%) patients had a diagnosis of autoimmune disorder, and 18 (5.6%) patients of a chronic infection. Multivariate analysis for progression to MM revealed an increased A/N ratio as the main independent prognostic variable. In addition, our study found a significant association between a reduced A/N ratio and the diagnosis of a chronic immune response related condition. Using receiver-operating characteristic analysis we created an A/N ratio range from 4 to 0.20. Values of 4 or higher define a group of MGUS patients at high risk of progression (OR, 10.7; 95% confidence interval 4.2-39), whereas A/N ratio values of 0.20 or lower are associated with immune disorders or chronic infections (OR, 20.9; 95% confidence interval 8.5-51.1). A total of 282 patients had an A/N ratio below 4, and 42 had values equal to or above the cut-off. Patients with an A/N ratio ≥ 4 had a cumulative probability of transformation of 35% at 5 years, compared with 3% for those with an A/N ratio 〈 4. Conclusions: Extreme values of the A/N ratio at diagnosis seem to be related with two different conditions: high risk MGUS, likely to progress to MM, and immune condition related MGUS. Our findings further support the routine use of phenotypic characterization of bone marrow plasma cells in patients with MGUS at diagnosis. Disclosures: No relevant conflicts of interest to declare.