Home » Key Clinical Research Articles Global Medical Discovery » Low-dose lenalidomide plus cytarabine induce complete remission that can be predicted by genetic profiling in elderly acute myeloid leukemia patients

Low-dose lenalidomide plus cytarabine induce complete remission that can be predicted by genetic profiling in elderly acute myeloid leukemia patients

Visani G1, Ferrara F2, Di Raimondo F3, Loscocco F1, Sparaventi G1, Paolini S4, Fuligni F4, Gazzola A4, Rossi M4, Laginestra MA4, Caraci MR3, Riccardi C2,Rocchi M5, Visani A4, Pileri SA4, Piccaluga PP4, Isidori A1.

Leukemia. 2014 Apr;28(4):967-70.

1Hematology and Hematopoietic Stem Cell Transplant Center, AORMN, Pesaro, Italy and

2Hematology, Cardarelli Hospital, Napoli, Italy and

3Hematology, Catania University, Catania, Italy and

4Hematopathology Section, Department of Experimental, Diagnostic, and Specialty Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy and

5Institute of Biomathematics, Urbino University, Urbino, Italy.

 

Abstract

 

A letter to the editor is presented on lenalidomide plus cytarabine induce which induced remission that can be predicted by genetic profiling in older people with acute myeloid leukemia.

 

Go To PubMed

 

Significance Statement

Background: outcome for older patients with acute myeloid leukaemia (AML) is extremely poor, especially for patients aged more than 70 years. Intensive induction chemotherapy is often unsuitable.

Methods: in this phase II study AML patients aged 70 years or older, ineligible for standard therapy, were consecutively treated with low-dose lenalidomide (10 mg/day orally, days 1-21) plus low-dose cytarabine (10mg/m2 twice daily, subcutaneously, days 1-15) every six weeks, up to 6 cycles. Thirty-three patients (median age 76 years) had intermediate (49%), unfavorable (45%) or unknown (6%) cytogenetic risk. Thirteen patients presented with de novo AML, twenty with secondary AML.

Findings: complete remission (CR) rate was 34% according to intention-to-treat. However, CR rate was 42% among patients evaluable after 1 cycle of therapy. Responding patients had a longer median overall survival than non-responders (559 vs. 52 days, P <0.0001). The CR rate was significantly higher in patients presenting with bone marrow blasts <30% (p=0.03). Cytogenetic risk was not predictive of CR. Conversely, by studying the global gene expression profiles, we identify a molecular signature, including 114 genes associated with the clinical response (CR versus no CR). The involved genes belonged to relevant functional categories, such as angiogenesis, cell cycle regulation and immune response. Based on the expression of a minimal set of 5 genes, we developed an algorithm to predict treatment response, that was successfully validated by showing an overall accuracy of 87%.

Interpretation: the combination of low-dose lenalidomide and low-dose cytarabine induces a high rate of CR that can be predicted by genetic profiling in a subset of elderly AML patients with extremely poor prognosis, unsuitable for intensive chemotherapy. The study was registered at EMA with the EUDRACT no 2008-006790-33.

 

Low-dose lenalidomide plus cytarabine induce complete remission that can be predicted by genetic profiling in elderly acute myeloid leukemia patients