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Updated analysis of CALGB 100104 (Alliance): a randomised phase III study evaluating lenalidomide vs placebo maintenance after single autologous stem cell transplant for multiple myeloma
- Source :
- The Lancet. Haematology
- Publication Year :
- 2017
-
Abstract
- In the CALGB (Alliance) 100104 study, lenalidomide versus placebo after autologous stem-cell transplantation (ASCT) was investigated for patients with newly diagnosed myeloma. That study showed improved time to progression and overall survival and an increase in second primary malignancies for lenalidomide at a median follow-up of 34 months. Here we report an updated intention-to-treat analysis of CALGB (Alliance) 100104 at a median follow-up of 91 months.Patients were eligible for this randomised, double-blind, placebo-controlled, phase 3 trial if they had symptomatic disease requiring treatment; had received, at most, two induction regimens; and had achieved stable disease or better in the first 100 days after ASCT. We randomly assigned patients to either lenalidomide or placebo groups using permuted block randomisation, with a fixed block size of six. Randomisation was stratified by three factors: normal or elevated β2 microglobulin concentration at registration (≤2·5 mg/L vs2·5 mg/L), previous use or non-use of thalidomide during induction therapy, and previous use or non-use of lenalidomide during induction therapy. The starting dose was two capsules (10 mg) per day, escalated to three capsules (15 mg) per day after 3 months. The primary endpoint was time to progression (time of progressive disease or death from any cause), with intention-to-treat analysis. This study is registered with ClinicalTrials.gov, identifier NCT00114101. New patients are no longer being recruited, but some patients remain on treatment and in follow-up.Between April 14, 2005, and July 2, 2009, 460 patients were randomly assigned to receive either lenalidomide (n=231) or placebo (n=229). After three interim analyses, the study was unblinded at a median follow-up of 18 months, at which point 86 (67%) of 128 patients without progressive disease in the placebo group chose to cross over to the lenalidomide group. The median follow-up for the updated survival analysis, as of Oct 19, 2016, was 91 months (IQR 83·6-103·1). The median time to progression was 57·3 months (95% CI 44·2-73·3) for the lenalidomide group and 28·9 months (23·0-36·3) for the placebo group (hazard ratio 0·57, 95% CI 0·46-0·71; p0·0001). The most common grade 3-4 adverse events were neutropenia (116 [50%] patients in the lenalidomide group and 41 [18%] patients in the placebo group) and thrombocytopenia (34 [15%] patients in the lenalidomide group and 12 [5%] patients in the placebo group). 18 (8%) haematological and 14 (6%) solid tumour second primary malignancies were diagnosed after randomisation and before disease progression in the lenalidomide group, compared with three (1%) haematological and nine (4%) solid tumour second primary malignancies in the placebo group. Three haematological and five solid tumour second primary malignancies in the placebo group were in the crossover subgroup.Despite an increase in haematological adverse events and second primary malignancies, lenalidomide maintenance therapy after ASCT significantly improved time to progression and could be considered a standard of care.The National Cancer Institute.
- Subjects :
- Adult
Male
medicine.medical_specialty
Placebo
Transplantation, Autologous
Article
Placebos
03 medical and health sciences
Young Adult
0302 clinical medicine
Maintenance therapy
Double-Blind Method
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Clinical endpoint
Humans
Lenalidomide
Multiple myeloma
business.industry
Hematopoietic Stem Cell Transplantation
Hematology
Middle Aged
medicine.disease
Survival Analysis
3. Good health
Surgery
Thalidomide
Transplantation
030220 oncology & carcinogenesis
Female
business
Multiple Myeloma
Progressive disease
030215 immunology
medicine.drug
Follow-Up Studies
Subjects
Details
- Language :
- English
- ISSN :
- 23523026
- Volume :
- 4
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- The Lancet. Haematology
- Accession number :
- edsair.doi.dedup.....5885770bf20d691c1eaaba4dba197a56