ORLANDO, Fla.—Lower-dose lenalidomide in combination with dexamethasone may significantly reduce incidence of hematologic toxicities, infections, and venous thromboembolism, without compromising treatment efficacy in patients with relapsed/refractory multiple myeloma who are ≥60 years of age or who have renal impairment, results of a planned interim analysis of a prospective multicenter phase 2 trial have indicated.

Previously, two phase 3 trials (US: MM-009; International: MM-010) have demonstrated the efficacy of standard-dose lenalidomide (25 mg days 1-21) and dexamethasone (40 mg days 1-4, 9-12, and 17-20) in relapsed/refractory multiple myeloma, Hang Quach, MBBS, FRACP, FRCPA, MD, of Monash University, Melbourne, Australia, and colleagues reported. However, in patients who were elderly or had renal impairment, toxicities were often observed, necessitating dose reductions.

Since multiple myeloma is a disease of the elderly and up to 50% of patients present with baseline renal impairment, this study investigated efficacy and tolerability of lower-dose lenalidomide (15 mg/d, days 1-21 q28d) and dexamethasone (20 mg/d days 1-4, 9-12, and 17-20 q28d for 4 cycles followed by 20 mg/d days 1-4 q28d) until disease progression in patients with relapsed/refractory multiple myeloma aged ≥60 years, and/or with creatinine clearance (CrCL) ≤60ml/min, the investigators noted in a poster presentation during the 52nd American Society of Hematology Annual Meeting and Exposition.

Study accrual (n=150) was completed in July 2010. In a planned interim analysis conducted in October 2009, response was analyzed in 75 patients who had completed ≥4 treatment cycles (range, 4-24 cycles). Median age was 68 years (range, 50-86 years). A median of 3 prior lines of treatment (range 1-7) had been administered, and 38% of patients had at least moderate renal impairment with CrCL ≤60ml/min at baseline. By EBMT (European Group for Blood and Marrow Transplantation) response criteria, 69% of patients achieved ≥PR (65% PR, 4% CR), comparable to the MM-009 (≥PR 60%) and MM-010 (≥PR 61%) trials.

By Independent Response Committee criteria, 69% of patients achieved ≥PR (42% PR; 23% VGPR; 2% CR; 2% sCR). Median time to progression (TTP) was 13 months—again, comparing favorably with the MM-009 (11.1 months) and MM-010 trials (11.3 months), Dr. Quach noted. Median OS has not been reached. Patients with CrCL ≤60 ml/min (n=28) had similar ORR (73%) to patients with normal renal function, consistent with prior subanalyses from the MM-009 and MM-010 trials.

Toxicity was assessable in 124 patients who received at least 1 treatment cycle. Compared to that reported with standard-dose lenalidomide-dexamethasone in MM-009 and MM-010, incidence of grade 3/4 neutropenia (13% vs 41%, 30%), thrombocytopenia (3% vs 15%, 12%) and anemia (2% vs 13%, 9%) was much lower. Patients with CrCL ≤60 ml/min did not experience higher incidences of grade ≥3 hematologic or nonhematologic toxicities. Incidence of infections (8% vs 21% for MM-009 and 10% for MM-010) and VTE (4.8% vs 20%, 15%) were notably lower than that reported with standard-dose lenalidomide-dexamethasone in the two trials. This may be related to the lower dose of dexamethasone used, as suggested by results of the ECOG E4A03 study in the front-line setting.

The investigators plan to perform a formal comparison of all 150 patients in this study with a matched cohort of patients receiving standard-dose lenalidomide-dexamethasone from the MM-009 and MM-010 trials to consolidate all findings.