title: A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial.
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.
  
  
  BACKGROUND
  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.
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cai
authors.forename: Fangping
authors.initials: F
authors.lastname: Chen
authors.forename: Dao-bin
authors.initials: DB
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ke
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
authors.forename: Fanyi
authors.initials: F
authors.lastname: Meng
authors.forename: Huisheng
authors.initials: H
authors.lastname: Ai
authors.forename: Jingshan
authors.initials: J
authors.lastname: Zhang
authors.forename: Honeylet
authors.initials: H
authors.lastname: Wortman-Vayn
authors.forename: Nianhang
authors.initials: N
authors.lastname: Chen
authors.forename: Jay
authors.initials: J
authors.lastname: Mei
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002681:China; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide