Analysis of Pomalidomide Plus Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma with Vs without Moderate Renal Impairment

Abstract Introduction: Renal impairment (RI) occurs in ≈ 20% to 40% of patients (pts) with multiple myeloma (MM; Kastritis et al, Haematologica, 2007) and is a major comorbidity with this disease (Korbet et al, J Am Soc Nephrol, 2006). Pts with MM who relapse on or become refractory to treatment (Tx) experience shortened overall survival (OS; Kumar et al, Leukemia, 2012). Pomalidomide + low-dose dexamethasone (POM + LoDEX) is approved for the Tx of relapsed/refractory MM (RRMM) in pts who have had Tx failure with lenalidomide and/or bortezomib. POM + LoDEX demonstrated safety and efficacy in pts with RRMM (MM-010; Dimopoulos et al, EHA 2015) as well as extended progression-free survival (PFS) and OS vs high-dose dexamethasone (MM-003; San Miguel et al, Lancet Oncol, 2013) or POM alone (MM-002; Richardson et al, Blood, 2014). Each trial included pts with moderate RI, and this pooled analysis examines the safety and efficacy of POM + LoDEX in pts with moderate RI. Patients and Methods: Pts from MM-002, MM-003, and MM-010 who had received POM + LoDEX were grouped by RI status (with moderate RI [creatinine clearance (CrCl) ≥ 30 to < 60 mL/min] and without RI [CrCl ≥ 60 mL/min]) and assessed for safety and efficacy. Results: Overall, from the 3 trials, data from 356 pts with moderate RI and 716 pts without RI were analyzed. Pts with moderate RI were slightly older (70 vs 63 yrs) and more commonly had International Staging System stage III disease (45.8% vs 25.4% in the 271 and 544 pts with available data). Median time from diagnosis was similar, 5.2 yrs (with moderate RI) vs 5.3 years (without RI); pts in both subgroups had a median of 5 prior Tx. The proportions of pts with moderate RI vs without RI who were refractory to LEN (95.5% vs 93.0%), BORT (82.0% vs 80.7%), and both LEN and BORT (78.4% vs 76.1%) were similar. The median Tx duration was slightly shorter for pts with moderate RI vs without RI (16.6 vs 20.4 weeks), but the median average daily dose (4.0 mg/day) and median relative dose intensity (0.9) were the same between renal subgroups. There were similar frequencies of discontinuations (7.4% vs 5.8%), dose reductions (22.7% vs 21.1%), and interruptions (63.1% vs 63.5%) due to adverse events (AEs) between subgroups of pts with moderate RI vs without RI. The most common grade 3/4 AEs for pts with moderate RI vs without RI were neutropenia (45.5% vs 48.3%), anemia (34.9% vs 27.5%), infections (31.3% vs 32.3%), and thrombocytopenia (21.3% vs 22.6%). The frequency of deep vein thrombosis/pulmonary embolism or peripheral neuropathy was ≤ 2% in both subgroups. The overall response rate (ORR) was 32.0% vs 33.0%, the median PFS was 18.1 weeks (95% CI, 15.6-20.9 weeks) vs 21.1 weeks (95% CI, 19.0-24.3 weeks), and median time to progression (TTP) was 20.3 weeks (95% CI, 17.3-24.1 weeks) vs 24.0 weeks (95% CI, 20.1-25.6 weeks) in pts with vs without moderate RI, respectively. Consistent with the poor prognosis associated with RI, median OS was shorter for pts with moderate RI (45.6 weeks [95% CI, 37.9-50.1 weeks]) vs those without RI (62.7 weeks [95% CI, 54.9-70.3 weeks]). Conclusions: In a pooled analysis of 3 trials of pts with RRMM treated with POM + LoDEX, ORR, PFS, TTP, and tolerability results appeared to be independent of the presence or absence of moderate RI. This analysis supports the use of POM + LoDEX as a standard of care in RRMM for pts with or without moderate RI. Disclosures Siegel: Celgene Corporation: Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Merck: Speakers Bureau; Novartis: Speakers Bureau. Weisel:Amgen: Consultancy, Honoraria, Other: Travel Support; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Travel Support, Research Funding; Novartis: Other: Travel Support; Onyx: Consultancy, Honoraria; Noxxon: Consultancy; BMS: Consultancy, Honoraria, Other: Travel Support. Dimopoulos:Genesis: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Onyx: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Janssen-Cilag: Honoraria. Baz:Karyopharm: Research Funding; Millennium: Research Funding; Celgene Corporation: Research Funding; Sanofi: Research Funding. Richardson:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Millennium Takeda: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees. Delforge:Celgene Corporation: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Song:Celgene Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. San Miguel:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees. Moreau:Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yu:Celgene Corporation: Employment, Equity Ownership. Hong:Celgene Corporation: Employment, Equity Ownership. Sternas:Celgene Corporation: Employment, Equity Ownership. Zaki:Celgene Corporation: Employment, Equity Ownership. Palumbo:Novartis, Sanofi Aventis: Honoraria; Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria.

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