1. Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes.
- Author
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Sekeres, Mikkael A., Tiu, Ramon V., Komrokji, Rami, Lancet, Jeffrey, Advani, Anjali S., Afable, Manuel, Englehaupt, Ricki, Juersivich, Joyce, Cuthbertson, David, Paleveda, Jennifer, Tabarroki, A.N., Visconte, Valeria, Makishima, Hideki, Jerez, Andres, Paquette, Ronald, List, Alan F., and Maciejewski, Jaroslaw P.
- Subjects
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MYELODYSPLASTIC syndromes treatment , *AZACITIDINE , *CELLULAR control mechanisms , *FEBRILE neutropenia , *CARCINOGENESIS - Abstract
Lenalidomide and azacitidine each have activity in myelodysplastic syndromes (MDS) patients, where both microenvi-ronment and cell-regulatory mechanisms contribute to disease pathogenesis. The objective of this multicenter, phase 2 expansion trial was to determine the efficacy and safety of combination therapy with azacitidine (75 mg/m2/d for 5 days) and lenalidomide (10 mg/d for 21 days; 28-day cycle) in patients with higher-risk MDS. Among 36 patients enrolled (18 phase 1, 18 phase 2), median age was 68 years (range, 47-78 years) and follow-up was 12 months (range, 3-55 years). IPSS categories included intermediate-1 (n = 5 patients with excess blasts), intermediate-2 (20), and high (11). Common grade 3/4 nonhematologic adverse events included febrile neutropenia (22% of patients), other infection (11%), pulmonary (11%), cardiac (11%), constitutional (11%), and dermatologic (11%). The overall response rate (per modified MDS International Working Group criteria) was 72%: 16 patients (44%) achieved a complete response (CR), and 10 (28%) had hematologic improvement. Median CR duration was 17+ months (range, 3-39+); median overall survival was 37+ months (range, 7-55+) for CR patients, and 13.6 months for the entire cohort (range, 3-55). TET2DNMT3AIIDH1/2 mutational status was associated with response in a limited number of patients. The lenalidomide/azacitidine combination is well-tolerated and highly active in treating greater-risk MDS [ABSTRACT FROM AUTHOR]
- Published
- 2012
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