Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma

Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K (Impact Factor: 10.43). 08/2009; 23(11):2147-52. DOI: 10.1038/leu.2009.147
Source: PubMed


We present a pooled update of two large, multicenter MM-009 and MM-010 placebo-controlled randomized phase III trials that included 704 patients and assessed lenalidomide plus dexamethasone versus dexamethasone plus placebo in patients with relapsed/refractory multiple myeloma (MM). Patients in both studies were randomized to receive 25 mg daily oral lenalidomide or identical placebo, plus 40 mg oral dexamethasone. In this pooled analysis, using data up to unblinding (June 2005 for MM-009 and August 2005 for MM-010), treatment with lenalidomide plus dexamethasone significantly improved overall response (60.6 vs 21.9%, P<0.001), complete response rate (15.0 vs 2.0%, P<0.001), time to progression (median of 13.4 vs 4.6 months, P<0.001) and duration of response (median of 15.8 months vs 7 months, P<0.001) compared with dexamethasone-placebo. At a median follow-up of 48 months for surviving patients, using data up to July 2008, a significant benefit in overall survival (median of 38.0 vs 31.6 months, P=0.045) was retained despite 47.6% of patients who were randomized to dexamethasone-placebo receiving lenalidomide-based treatment after disease progression or study unblinding. Low beta(2)-microglobulin and low bone marrow plasmacytosis were associated with longer survival. In conclusion, these data confirm the significant response and survival benefit with lenalidomide and dexamethasone.

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Available from: Robert Douglas Knight, Sep 18, 2014
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    • "Such drugs have been credited with the improved survival of patients over the last 10 years (Kumar et al, 2008). In a pooled analysis of two large international randomized phase 3 clinical trials of 704 patients with relapsed MM (MM009/ 010), lenalidomide and dexamethasone demonstrated improvements in progression-free survival (PFS) (11Á1 vs. 4Á6 months), time to progression (TTP) (13Á4 vs. 4Á6 months) and overall survival (OS) (38Á0 vs. 31Á6 months) compared with high dose dexamethasone (Dimopoulos et al, 2009). As expected, this benefit was greater when used for patients at first relapse compared to those treated at later stages of their disease (Stadtmauer et al, 2009). "

    British Journal of Haematology 08/2014; 168(1). DOI:10.1111/bjh.13072 · 4.71 Impact Factor
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    • "This can complicate the treatment process of myeloma in the elderly, since NP may present as bradycardia and also constipation and impotence.74 Lenalidomide is a second-generation drug with more potency but less neurotoxicity.75 "
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    • "The best ORR with lenalidomide plus low-dose dexamethasone in the MM-021 analysis was slightly lower than the best ORR in the MM-009 and MM-010 studies (47.6% vs. 60.6%, respectively) [6,7,18], perhaps explained by dexamethasone dosing and disease severity differences. In the pivotal studies, dexamethasone was given at an intense dose and schedule for the first 4 cycles (40 mg on days 1–4, 9–12, and 17–20; 480 mg per cycle), compared with the low-dose dexamethasone given in the MM-021 study (40 mg on days 1, 8, 15, and 22; 160 mg per cycle). "
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    ABSTRACT: BACKGROUND: There is an unmet need for treatment options in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Lenalidomide plus low-dose dexamethasone is effective and generally well tolerated in Caucasian RRMM patients, but no previous study has evaluated this regimen in Chinese RRMM patients. METHODS: MM-021 is a phase 2, multicenter, single-arm open-label registration trial conducted to assess the efficacy, safety, and pharmacokinetics of lenalidomide plus low-dose dexamethasone in Chinese patients with RRMM. Patients with >=1 prior antimyeloma therapy received lenalidomide plus low-dose dexamethasone until disease progression or discontinuation. Follow-up of surviving patients continued for >=1 year after enrollment. The lenalidomide dose was 25 mg/day, and was adjusted according to baseline renal function. Most patients had advanced disease (85.6% had Durie-Salmon stage III) and were heavily pretreated (56.7% had received >=4 prior regimens; 69.5% prior thalidomide and 63.1% prior bortezomib); 5.3% had immunoglobulin D (IgD) disease. RESULTS: The safety population comprised 199 eligible patients. In the efficacy population (n = 187), the disease control rate (at least stable disease) was 94.7%, and the overall response rate (at least partial response) was 47.6%. High response rates were also achieved in patients who had renal impairment and in those with IgD disease. After a median study follow-up of 15.2 months, the median response duration was 8.8 months (range, 0.4--18.8 months) and median progression-free survival was 8.3 months (95% CI 6.5--9.8). The most common grade 3--4 adverse events (AEs) were anemia (26.1%), neutropenia (25.1%), thrombocytopenia (14.6%), pneumonia (13.1%), leukopenia (9.5%), and decreased neutrophil count (8.5%). AEs led to lenalidomide dose reduction and/or interruption in 40.2% of patients, and treatment discontinuation in about 9% of patients. The pharmacokinetic profile of lenalidomide was similar to that reported in Caucasian and Japanese patients. CONCLUSIONS: Lenalidomide plus low-dose dexamethasone was associated with a high response rate and acceptable safety profile in heavily pretreated Chinese patients with RRMM, including those with renal impairment and IgD subtype. These findings highlight the clinical potential of this regimen in Chinese RRMM patients who have exhausted current treatment options.Trial registration: China State Food and Drug Administration (SFDA) registration (CTA reference numbers: 209 L10808; 209 L10809; 209 L10810; and 209 L10811) and ClinicalTrials.gov identifier: NCT01593410.
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