Low-dose lenalidomide plus cytarabine in very elderly, unfit acute myeloid leukemia patients: Final result of a phase II study

Abstract

Outcome for elderly patients with acute myeloid leukemia (AML) is extremely poor. Intensive induction chemotherapy is often unsuitable. Sixty-six newly diagnosed AML patients (median age: 76years), ineligible for standard therapy, were consecutively treated with low-dose lenalidomide (10mg/day orally, days 1-21) plus 10mg/m low-dose cytarabine, subcutaneously, twice a day (days 1-15) every six weeks, up to 6 cycles. Complete remission (CR) rate was 36.3% according to intention-to-treat. Responding patients had a longer median overall survival than non-responders (517 vs. 70days, P<0.001). The achievement of CR was not predicted by bone marrow blast count, cytogenetics, molecular markers, prior MDS, white blood cell count. Conversely, by studying the global gene expression profile, we identified a molecular signature, including 309 genes associated with clinical response (CR versus no CR). Based on the expression of a minimal set of 16 genes, we developed an algorithm to predict treatment response, that was successfully validated by showing an overall accuracy of 88%. We met the primary endpoint of the study, by beating the estimated successful CR rate (P1) fixed at 30%. Moreover, CR induced by this 2-drug combo was efficiently predicted by genetic profiling, identifying a biomarker that warrants validation in independent series.

Genomic Profiling and Predicting Treatment Response in Acute Myeloid Leukemia

“…Very recently, our group has shown the prospective use of a GEP-driven therapy in a cohort of hard-to-treat AML patients, unfit for standard therapy, with an extremely poor prognosis [18,19]. 66 unfit AML patients aged >70 years received low-dose lenalidomide plus low dose cytarabine [18,19] By studying the global GEP of AML blasts collected before treatment administration, we were able to identify five genes efficiently discriminating patients who did or did not obtain CR.…”

“…Very recently, our group has shown the prospective use of a GEP-driven therapy in a cohort of hard-to-treat AML patients, unfit for standard therapy, with an extremely poor prognosis [18,19]. 66 unfit AML patients aged >70 years received low-dose lenalidomide plus low dose cytarabine [18,19] By studying the global GEP of AML blasts collected before treatment administration, we were able to identify five genes efficiently discriminating patients who did or did not obtain CR. Such signature showed a predictive accuracy of 88% in the original paper [18,19] Although the 5-gene signature seems to be treatment-specific, and needs a validation in an independent cohort of patients, this is a new scenario for drug development in AML, in which the definition of accurate biomarkers may help discriminate those patients who may or may not benefit from a specific targeted therapy.…”

Efficacy and safety of lenalidomide for the treatment of acute myeloid leukemia: a systematic review and meta-analysis

“…After exclusion, based on title and abstract, 21 full-text articles were reviewed and eleven observational studies were included. 18 – 20 , 25 – 32 Screening of the reference lists for additional studies or referring articles did not yield any further articles for inclusion. Figure 1 shows a flowchart for study selection.…”

Immunomodulatory Drugs in Acute Myeloid Leukemia Treatment

“…This trial was associated with marked skin toxicity and other toxicities such as nausea, vomiting, mucositis, electrolyte disturbances. In a second study, Visani et al [ 44 ] described 66 elderly AML patients (median age 76 years) ineligible for intensive chemotherapy or allotransplantation, who were consecutively treated with low dose lenalidomide (10 mg/day, days 1–21) plus low dose cytarabine (10 mg/m2, twice a day, on days 1–15, every six weeks, up to 6 cycles). The rate of CR was 36% and its achievement was not predicted by bone marrow blast count, molecular markers, cytogenetics, white blood cell count or prior MDS.…”