Abstract

Background

In China, the combination of lenalidomide (LEN) and low-dose dexamethasone (LoDEX) is approved for the treatment of RRMM patients (pts) who have received at least 1 prior therapy, based on data from the MM-021 China registration study. In RRMM pts, impaired renal function is a leading cause of comorbidity and early death. In addition, in RRMM pts renal impairment (RI) is associated with poor ECOG performance scores. In this MM-021 subgroup analysis, efficacy and safety of LEN + LoDEX (Rd) were evaluated in pts with RI. As LEN excretion is predominantly renal, LEN plasma concentrations are higher and LEN half-life is longer in pts with RI.  Consequently, lower starting doses of LEN are needed for pts with RI in order to ensure adequate safety while maintaining therapeutic efficacy.

Methods

MM-021 was a phase 2, multicenter, single-arm, open-label study. Pts with RRMM received LEN (25 mg/day on days 1–21) and LoDEX (40 mg/day on days 1, 8, 15, and 22) in 28-day treatment cycles until disease progression or discontinuation. Pts included in the pharmacokinetics cohort did not receive LoDEX on day 1, cycle 1. The LEN starting dose was adjusted according to baseline creatinine clearance (CrCl): 25 mg/day for pts with normal renal function (CrCl ≥ 60 mL/min), 10 mg/day for pts with moderate RI (CrCl 30 to < 60 mL/min), or 15 mg every other day for pts with severe RI (CrCl < 30 mL/min). All pts received thromboprophylaxis during the study. The primary end-point was best overall response rate (ORR), defined as percentage of pts who achieved a best response of partial response or better. Time to progression, progression-free survival, overall survival and safety were evaluated as secondary end-points.

Results

At the data cut-off (January 4, 2013; median follow-up 17.6 mos), 199 pts (intent-to-treat population) were evaluable for safety and 187 pts for efficacy. At the cut-off date, 42 pts had completed their treatment, and 157 had discontinued treatment. At baseline, 27.1% ( n= 54) of pts had moderate RI, 7% (n = 14) had severe RI, and 65.8% (n = 131) had normal renal function.  ORR was higher in pts with normal renal function compared with those with moderate or severe RI (Table 1). In pts with normal renal function or moderate RI, the rates of grade 3-4 neutropenia (26% and 20.4%, respectively), anemia (21.4% and 29.6%, respectively), and thrombocytopenia (10.7% and 13.0%, respectively) were similar and comparable to the overall population. In pts with severe RI, rates of grade 3-4 neutropenia, anemia, and thrombocytopenia were higher (35.7%, 57.1%, and 57.1%, respectively). There were 2 reports of grade 3-4 peripheral neuropathy. Discontinuation of Rd due to adverse events was reported in 5.3% of pts with normal renal function, 13% of those with moderate RI, and 28.6% of pts with severe RI.

Conclusions

Adjusting the starting dose of LEN in RRMM pts with moderate or severe RI did not compromise treatment efficacy. ORR was highest in pts with normal renal function but pts with moderate and severe RI still achieved high ORRs and Rd was well tolerated.

Disclosures:

Zhang:Celgene Corporation: Employment, Equity Ownership. Wortman-Vayn:Celgene Corporation: Employment, Equity Ownership. Mei:Celgene: Employment, Equity Ownership. Hou:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees; J & J: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Author notes

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Asterisk with author names denotes non-ASH members.