Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes.
Lenalidomide and azacitidine each have activity in myelodysplastic syndromes (MDS) patients, where both microenvironment 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/m(2)/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). TET2/DNMT3A/IDH1/2 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.
Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave, Cleveland, OH 44195, USA. sekerem@ccf.org
Mikkael A
MA
Sekeres
Ramon V
RV
Tiu
Rami
R
Komrokji
Jeffrey
J
Lancet
Anjali S
AS
Advani
Manuel
M
Afable
Ricki
R
Englehaupt
Joyce
J
Juersivich
David
D
Cuthbertson
Jennifer
J
Paleveda
Ali
A
Tabarroki
Valeria
V
Visconte
Hideki
H
Makishima
Andres
A
Jerez
Ronald
R
Paquette
Alan F
AF
List
Jaroslaw P
JP
Maciejewski
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007621:Karyotyping; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D013792:Thalidomide; D000077269:Lenalidomide; D001374:Azacitidine