Dose escalation of lenalidomide in relapsed or refractory acute leukemias.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Division of Hematology, The Ohio State University and The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA. william.blum@osumc.edu
William
W
Blum
Rebecca B
RB
Klisovic
Heiko
H
Becker
Xiaoxia
X
Yang
Darlene M
DM
Rozewski
Mitch A
MA
Phelps
Ramiro
R
Garzon
Alison
A
Walker
Jason C
JC
Chandler
Susan P
SP
Whitman
John
J
Curfman
Shujun
S
Liu
Larry
L
Schaaf
Jon
J
Mickle
Cheryl
C
Kefauver
Steven M
SM
Devine
Michael R
MR
Grever
Guido
G
Marcucci
John C
JC
Byrd
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D000077269:Lenalidomide; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence; D063268:Sialic Acid Binding Ig-like Lectin 3; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D013792:Thalidomide; D000077269:Lenalidomide