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: 18.43). 10/2010; 28(33):4919-25. DOI: 10.1200/JCO.2010.30.3339
Source: PubMed


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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Available from: Jason Chandler, Jul 28, 2015
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    • "A phase 1 study in relapsed/refractory AML patients also indicated that lenalidomide can be tolerated up to 50 mg daily, but there were no CR's in the del5q population. Those that did respond had low presenting white cell counts suggesting limited efficacy as monotherapy in proliferative disease [8] Additionally, the Nordic group had similar findings when they assessed lenalidomide monotherapy up to 20 mg daily in a phase 2 study for MDS/AML patients with any form of chromosome 5 abnormality and noted no response in patients with TP53 mutation [9]. More recently a phase 1 study of sequential therapy with azacitidine and lenalidomide has identified an alternative approach capable of inducing haematological improvement and complete cytogenetic remissions, although has significant haematological toxicity [10]. "
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    • "Interestingly, 2 of 4 patients who had relapsed after an allogeneic stem cell transplant developed acute graft versus host disease of the skin and durable CR. Toxicities included fatigue and infection, but high dose lenalidomide was relatively well-tolerated.41 SWOG conducted a phase II clinical trial for untreated elderly patients with 5q deletion with or without additional cytogenetic abnormalities. "
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