ECOG Performance Status Affects Efficacy, but Not Safety, of Lenalidomide/Dexamethasone in Relapsed/Refractory Multiple Myeloma (MM009/010 Sub-Analysis).

Abstract Background: Eastern Cooperative Oncology Group (ECOG) performance status is a prognostic factor in patients with multiple myeloma (MM). Lenalidomide (Len) is an oral immunomodulatory drug that is effective against relapsed/refractory MM (rrMM). In 2 prospective, randomized, double–blind, placebo–controlled phase III trials in patients with rrMM (MM–009 and MM–010), the combination of Len/Dexamethasone (Dex) induced a significantly higher overall response (OR) rate and complete response (CR) rate, as well as significantly longer overall survival (OS) and time–to–progression (TTP), compared with Dex alone. To investigate whether patients’ performance status has an impact on clinical response, we compared the efficacy and tolerability of Len/Dex in patients with baseline ECOG score =0 and >0. Methods: Data for patients with a baseline ECOG score recorded were pooled from the MM-009 and MM-010 studies (n= 690). Patients were randomized to receive Len (25 mg/day on days 1–21 of each 28–day cycle), or placebo. Both groups received Dex 40 mg PO q.d. on days 1–4, 9–12, and 17–20 (for the first 4 cycles). After 4 cycles, Dex 40 mg/day was administered only on days 1–4. Response to therapy, TTP, OS, and adverse events (AE) were assessed. Response rate and TTP are based on data obtained before unblinding (June 2005 [MM–009] and August 2005 [MM–010]). Results: Of 302 patients with an ECOG score of 0 at baseline, 152 were treated with Len/Dex and 150 with Dex alone. For those with an ECOG score >0, 192 received Len/Dex and 196 received Dex alone. Baseline characteristics were balanced between treatment groups. Patients with baseline ECOG score ≥0 had significantly higher OR rates with Len/Dex (59% and 62%, respectively) compared with Dex alone (both 22%; Table). In both ECOG groups, Len/Dex resulted in a significantly longer median TPP compared with Dex alone. In those with ECOG score >0, a significant improvement in OS was noted with Len/Dex treatment. No difference in median TTP was observed between patients with ECOG score ≥0 among Len/Dex-treated patients. Also, ECOG status did not affect tolerability profiles. Grade 3–4 hematological AE in patients with ECOG ≥0 treated with Len/Dex were higher than those treated with Dex alone and included neutropenia (31–39% vs 3–4%), thrombocytopenia (13–13% vs 4–8%), and anemia (9–12% vs 5–7%). Febrile neutropenia was reported in ≤3% of patients. Conclusion: Len/Dex was superior to Dex alone in patients with rrMM. This superiority of Len/Dex was irrespective of baseline performance status of the patients enrolled. Based on this analysis, we conclude that Len/Dex is an important therapeutic option in patients with rrMM despite suboptimal performance status. ECOG=0 ECOG>0 Len/Dex (n=152) Dex (n=150) P Len/Dex (n=192) Dex (n=196) P Clinical response, % OR 59 22 <0.001 62 22 <0.001 CR 12 1 <0.001 16 3 <0.001 PR 39 20 <0.001 35 18 <0.001 Median TTP, weeks 44.3 20.1 <0.001 57.0 20.1 <0.001 Median OS, weeks 156.0 159.1 NS 141.6 103.7 <0.01