Article

Dose escalation of lenalidomide in relapsed or refractory acute leukemias.

Division of Hematology, The Ohio State University and The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Journal of Clinical Oncology (impact factor: 18.37). 10/2010; 28(33):4919-25. DOI:10.1200/JCO.2010.30.3339 pp.4919-25
Source: PubMed

ABSTRACT Lenalidomide is effective in myeloma and low-risk myelodysplastic syndromes with deletion 5q. We report results of a phase I dose-escalation trial of lenalidomide in relapsed or refractory acute leukemia.
Thirty-one adults with acute myeloid leukemia (AML) and four adults with acute lymphoblastic leukemia (ALL) were enrolled. Lenalidomide was given orally at escalating doses of 25 to 75 mg daily on days 1 through 21 of 28-day cycles to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD), as well as to provide pharmacokinetic and preliminary efficacy data.
Patients had a median age of 63 years (range, 22 to 79 years) and a median of two prior therapies (range, one to four therapies). The DLT was fatigue; 50 mg/d was the MTD. Infectious complications were frequent. Plasma lenalidomide concentration increased proportionally with dose. In AML, five (16%) of 31 patients achieved complete remission (CR); three of three patients with cytogenetic abnormalities achieved cytogenetic CR (none with deletion 5q). Response duration ranged from 5.6 to 14 months. All responses occurred in AML with low presenting WBC count. No patient with ALL responded. Two of four patients who received lenalidomide as initial therapy for AML relapse after allogeneic transplantation achieved durable CR after development of cutaneous graft-versus-host disease, without donor leukocyte infusion.
Lenalidomide was safely escalated to 50 mg daily for 21 days, every 4 weeks, and was active with relatively low toxicity in patients with relapsed/refractory AML. Remissions achieved after transplantation suggest a possible immunomodulatory effect of lenalidomide, and results provide enthusiasm for further studies in AML, either alone or in combination with conventional agents or other immunotherapies.

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Keywords

28-day cycles
 
31 patients
 
4 weeks
 
acute lymphoblastic leukemia
 
acute myeloid leukemia
 
cutaneous graft-versus-host disease
 
cytogenetic abnormalities
 
deletion 5q
 
donor leukocyte infusion
 
dose-limiting toxicity
 
Infectious complications
 
low-risk myelodysplastic syndromes
 
maximum-tolerated dose
 
Plasma lenalidomide concentration
 
possible immunomodulatory effect
 
preliminary efficacy data
 
refractory acute leukemia
 
relapsed/refractory AML
 
Response duration
 
responses