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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    • "These studies demonstrated the efficacy and safety of RD as compared with placebo and high-dose dexamethasone (PBO + DEX) in RRMM patients. In a pooled analysis of the 704 patients who participated in the MM-009 and MM- 010 trials, treatment with RD, compared with PBO + DEX, significantly improved response rate (60.6 vs 21.9 %, P < 0.001) and median OS (38.0 vs 31.6 months, P = 0.045), despite the fact that 47.6 % of patients randomized to PBO + DEX crossed over to the RD arm[10]. Few studies have assessed the long-term effects of treatment with lenalidomide plus dexamethasone in patients with RRMM, although available studies have consistently shown that long-term treatment was effective and well tolerated, with no increase in second primary malignancies (SPMs)111213. "
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    ABSTRACT: Background The efficacy and safety of lenalidomide plus low-dose dexamethasone (Rd) in Chinese patients with relapsed/refractory multiple myeloma (RRMM) was demonstrated in a phase 2, multicenter trial (MM-021). MM-024 was an Extended Access Program (EAP) that allowed responding patients in the MM-021 trial to continue to receive Rd, and to provide additional safety and efficacy data with longer follow-up. Methods Chinese patients with RRMM who completed ≥1 year of Rd therapy in MM-021 and who remained progression-free under Rd entered the Treatment Phase of the MM-024 EAP, continuing Rd at the same dose and schedule. Patients in MM-021 who discontinued Rd treatment or progressed were allowed to enroll in the Safety Follow-Up Phase of the MM-024 EAP. Safety data, including the incidence of second primary malignancies (SPMs), were collected for ≥5 years from the time the last on-study patient enrolled in the MM-021 trial (primary end point). Efficacy outcomes (time to progression [TTP], progression-free survival [PFS], and overall survival [OS]) were secondary end points. Results Median follow-up was 38.4 months for the safety population (n = 80) and 43.3 months for the treatment cohort (n = 41). In the safety population, Grade 3–4 adverse events (AEs) occurred in 60.0 % of patients; the most common grade 3–4 AEs were neutropenia (20.0 %), decreased neutrophil count (13.8 %), and anemia (11.3 %). There was no evidence of cumulative toxicity, and no patients discontinued Rd due to AEs; 2 patients had SPMs. In the treatment cohort, median duration of response was 35.1 months, median TTP was 36.9 months, and median PFS was 36.0 months; median OS was not reached due to the low number of deaths (n = 5). Conclusion Long-term treatment with Rd has a predictable and manageable safety profile and provides sustained efficacy in Chinese patients with RRMM. Trial registration China State Food and Drug Administration (SFDA) registration (CTA reference numbers: 209L10808; 209L10809; 209L10810; and 209L10811) and Identifier: NCT02348528. First received January 23, 2015; last updated November 12, 2015; last verified November 2015; study start date September 2012.
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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). "

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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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