Lower-Dose Lenalidomide and Dexamethasone Reduces Toxicity without Compromising Efficacy In Patients with Relapsed/Refractory Myeloma, Who Are Aged ≥60 Years or Have Renal Impairment: Planned Interim Results of a Prospective Multicentre Phase II Trial

Abstract 1961

Standard-dose lenalidomide (25mg D1-21) and dexamethasone (40mg D1-4,9-12,17-20) [len-dex] is efficacious in the treatment of relapsed/refractory multiple myeloma (MM) as demonstrated in the phase III MM010 and MM009 trials. However, toxicities were often seen in patients who were elderly or had renal impairment necessitating dose reductions. Given that MM is a disease of the elderly, and that up to 50% of patients with MM present with baseline renal impairment, we investigated the efficacy and tolerability of lower-dose lenalidomide (15mg/d, d1-21q28d) and dexamethasone (20mg/d d1-4,9-12,17-20 q28d for 4 cycles followed by 20mg/d d1-4 q28d) until disease progression, in patients with relapsed/refractory MM aged ≥60 years, and/or with CrCL ≤60ml/min. Accrual for this prospective multi-centre phase-II trial was complete as of July 2010 (n=150).

In a planned interim analysis (October 2009), response was analysed in 75 patients who had completed ≥4 treatment-cycles (range 4–24). These patients had a median age of 68 years (range 50–86), a median of 3 prior lines of treatment (range 1–7), and 38% of patients had at least moderate renal impairment with CrCL £60ml/min at baseline. By EBMT response-criteria, 69% of patients achieved ≥PR (65% PR, 4% CR), which was comparable to the MM009 and MM010 trials (≥PR 60–61%). By IRC response criteria, 69% of patients achieved ³PR (42% PR; 23% VGPR; 2% CR; 2% sCR). Median TTP was 13 months, again comparing favourably to the MM009 and MM010 trials (median TTP 11.1 and 11.3 months, respectively); median OS has not been reached. Patients with CrCL ≤60ml/min (n=28) had similar ORR (73%) to patients with normal renal function, consistent with prior subanalyses from MM009/MM010.

Toxicity was assessable in 124 patients who received at least 1 treatment-cycle. The incidence of Grade 3/4 neutropenia (13% vs. 30–41%), thrombocytopenia (3% vs 12–15%) and anaemia (2% vs. 9–13%) was much lower compared to that reported with standard-dose len-dex in MM010 and MM009. Importantly, patients with CrCL ≤60ml/min did not experience higher incidences of grade ≥3 haematologic or non-haematologic toxicities. The incidence of infections (8% vs. 10–21%) and veno-thromboembolism (VTE) (4.8% vs. 15–20%) were notably lower than that reported with standard-dose len-dex in the MM009 and MM101 trials. This may be related to the lower dose of dexamethasone used as suggested by the results from the ECOG E4A03 study in the front-line setting.