A study of high-dose lenalidomide induction and low-dose lenalidomide maintenance therapy for patients with hypomethylating agent refractory myelodysplastic syndrome.
Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by bone marrow failure which frequently progress to acute myeloid leukemia. Patients who fail to respond to, or progress on first-line DNA hypomethylating agents (HMA) have a poor prognosis. Conventionally dosed lenalidomide has activity in 5q-MDS. In other subtypes, it may reduce RBC transfusion requirements but does not result in cytogenetic responses. We previously reported that high-dose lenalidomide induction (50 mg/day) results in complete remissions in a high fraction of patients. We, therefore, conducted a Phase 2 trial of the same regimen in MDS refractory to HMA. Marrow complete remissions were seen in 33% of patients and hematological improvement in 8% of patients. Significant infections complicated more than 50% of cases. Future trials to explore alternative dosing schedules of high-dose lenalidomide to increase efficacy while decreasing toxicity are warranted.
a Department of Medicine, Division of Oncology , School of Medicine, Washington University , St. Louis , MO , USA ;
Mathew A
MA
Cherian
b Division of Hematology and Medical Oncology , Mayo Clinic Arizona , Scottsdale , AZ , USA ;
Raoul
R
Tibes
c Department of Surgery, Division of Public Health Sciences , School of Medicine, Washington University , St. Louis , MO , USA.
Feng
F
Gao
a Department of Medicine, Division of Oncology , School of Medicine, Washington University , St. Louis , MO , USA ;
Theresa
T
Fletcher
a Department of Medicine, Division of Oncology , School of Medicine, Washington University , St. Louis , MO , USA ;
Mark
M
Fiala
a Department of Medicine, Division of Oncology , School of Medicine, Washington University , St. Louis , MO , USA ;
Geoffrey L
GL
Uy
a Department of Medicine, Division of Oncology , School of Medicine, Washington University , St. Louis , MO , USA ;
Peter
P
Westervelt
a Department of Medicine, Division of Oncology , School of Medicine, Washington University , St. Louis , MO , USA ;
Meagan A
MA
Jacoby
a Department of Medicine, Division of Oncology , School of Medicine, Washington University , St. Louis , MO , USA ;
Amanda F
AF
Cashen
a Department of Medicine, Division of Oncology , School of Medicine, Washington University , St. Louis , MO , USA ;
Keith
K
Stockerl-Goldstein
a Department of Medicine, Division of Oncology , School of Medicine, Washington University , St. Louis , MO , USA ;
John F
JF
DiPersio
a Department of Medicine, Division of Oncology , School of Medicine, Washington University , St. Louis , MO , USA ;
Ravi
R
Vij
D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D012074:Remission Induction; D019233:Retreatment; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D007155:Immunologic Factors; D013792:Thalidomide; D000077269:Lenalidomide
Chemotherapeutic approaches; myeloid leukemias and dysplasias; pharmacotherapeutics