title: A phase 2 trial of high dose lenalidomide in patients with relapsed/refractory higher-risk myelodysplastic syndromes and acute myeloid leukaemia with trilineage dysplasia.
abstract: Limited therapies exist for patients with refractory and relapsed (RR) higher-risk myelodysplastic syndromes (HR-MDS) and acute myeloid leukaemia with trilineage dysplasia (AML-TD). High dose (HD) lenalidomide (50 mg) has activity as frontline therapy in elderly AML but there is limited data in the RR setting. This phase II trial included patients with RR HR-MDS or AML-TD at 2 doses of lenalidomide (15 or 50 mg) on days 1-28 of 42-day cycles. The primary endpoint was response rate using the 2006 International Working Group criteria. Overall survival (OS) was estimated by Kaplan-Meier methods. Of 27 patients enrolled, 59% had HR-MDS and 31% AML-TD. No patient had isolated del5q; 41% had poor-risk karyotype. Of 9 patients treated at 15 mg, 56% completed ≥2 cycles with no responses. Of 18 patients treated at 50 mg, 39% completed ≥2 cycles and 11% responded but all experienced grade 3/4 neutropenic fever/infection. The 60-day mortality rate was 30%. Median OS was 114 days with 19% surviving ≥1 year. The study was terminated due to lack of robust clinical activity. In conclusion, lenalidomide at 15 mg is ineffective in RR myeloid malignancies. Continous high dosing schedules are poorly tolerated and minimally active. Further evaluation should be considered in upfront intensive chemotherapy-ineligible patients.
authors: Department of Medicine, Yale University, New Haven, CT, USA.
authors: Amer M
authors: AM
authors: Zeidan
authors: Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
authors: B Douglas
authors: BD
authors: Smith
authors: Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, Cleveland, OH, USA.
authors: Hetty E
authors: HE
authors: Carraway
authors: Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
authors: Ivana
authors: I
authors: Gojo
authors: Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
authors: Amy
authors: A
authors: DeZern
authors: Department of Medicine, Yale University, New Haven, CT, USA.
authors: Steven D
authors: SD
authors: Gore
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D009503:Neutropenia / Q000139:chemically induced; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide
keywords: acute myeloid leukaemia; lenalidomide; myelodysplastic syndromes; refractory