PB2117 POMALIDOMIDE PLUS LOW‐DEXAMETHASONE TREATMENT FOR ≥ 1 YEAR IN PATIENTS WITH RELAPSED REFRACTORY MULTIPLE MYELOMA AND RENAL IMPAIRMENT: A SUBANALYSIS OF THE MM‐013 PHASE 2 STUDY
Authors: Weisel K. , Dimopoulos M. , Cook M. , Ramasamy K. , de La Rubia J. , Ardizzoia A. , Krauth M. T. , Jaccard A. , Van de Donk N. , Kueenburg E. , Di Micco A. , Rosettani B. , Atiba‐Davies M. , Bacon P. , Sonneveld P. 
Published: June 2019

Background:The combination of the immunomodulatory agent pomalidomide (POM) and dexamethasone (DEX) is approved in the European Union for patients (pts) with relapsed refractory multiple myeloma (RRMM), including those with renal impairment (RI). The MM‐013 (NCT02045017; EudraCT Number: 2013‐001903‐36) phase 2, noncomparative trial has demonstrated a benefit with POM + low‐dose dexamethasone (LoDEX) in pts with moderate RI, severe RI, and severe RI requiring hemodialysis (Dimopoulos M, et al. J Clin Oncol. 2018;36:2035‐2043.)Aims:To report efficacy and safety of ≥ 1 year of POM + LoDEX treatment (Tx) in RRMM pts with moderate or severe RI, including those on hemodialysis.MethodsThe study enrolled 3 cohorts: (A, n = 33)–moderate RI (estimated glomerular filtration rate [eGFR] 30 to < 45 mL/min/1.73 m2), (B, n = 34)–severe RI (eGFR < 30 mL/min/1.73 m2), and (C, n = 14)–severe RI requiring hemodialysis. Pts received 28‐day cycles of POM (4 mg/day on days 1 to 21) and LoDEX (40 mg/day; 20 mg/day if age > 75 yrs, on days 1, 8, 15, and 22). All pts must have received ≥ 1 prior Tx including lenalidomide and progressed during or after their last anti‐myeloma therapy before entering the study. Primary endpoint was overall response rate (ORR). All pts provided informed consent.Results:A total of 17 pts (21.0%) of 81 pts enrolled in this trial, received Tx for ≥ 1 year: 10 in cohort A, 6 in cohort B, and 1 in cohort C, of whom 2, 2, and 1 pt, respectively were still on Tx as of January 4, 2019. Overall, 12 pts (70.6%) discontinued Tx; 7 (41.2%) due to progressive disease, 3 (17.6%) due to adverse events (AEs), and 1 pt (5.9%) each due to death and withdrawal from Tx. Median age was 68 yrs (range, 55–86 yrs) and 64.7% of pts were male. Median number of prior lines of Tx was 3, 2, and 4 in cohorts A, B, and C, respectively. Median Tx duration was 19.8, 19.9, and 32.3 mos and median dose intensity was 4.1, 3.7, and 4.9 mg. Median modification of diet in renal disease eGFR was 40.6, 18.0, and 4.0 mL/min/1.73m2. Response rates are shown in Table 1. Median time to response was 1.4, 1.9, and 2.9 mos in cohorts A, B, and C, respectively. Median duration of response (DOR) was 14.7 mos for the 7 pts who progressed in cohort A. DOR was not estimable (NE) for the two other cohorts as 1 pt progressed in cohort B and the pt in cohort C was still on Tx. Renal response was 30.0%, 50.0%, and 0% (Table 1). Overall, median progression‐free survival was 25.8 mos (95% CI, 14.5‐NE). The most frequent grade 3/4 adverse events were neutropenia (6, 1, and 1 pt in cohorts A, B, and C, respectively), anemia (3, 3, and 1 pt), and infections (6, 2, and 1 pt). One pt in cohort A discontinued POM due to ≥ 1 AE. AE‐related POM dose reductions occurred in 3 and 2 pts in cohorts A and B, respectively. AE‐related POM dose interruptions occurred in 7, 6, and 1 pt in cohorts A, B, and C, respectively.Summary/Conclusion:This ongoing, noncomparative study confirms that Tx with POM + LoDEX is efficacious in RRMM pts with RI and can be tolerated for ≥ 1 year.image