Erythropoietic Therapy Does Not Interfere With Response to Imatinib in CML Patients

PORTLAND, Oregon—Giving erythropoietic therapy to chronic myelogenous leukemia (CML) patients does not appear to interfere with their response to imatinib mesylate (STI571, Gleevec) therapy, according to a retrospective study of 37 patients treated in the Leukemia Center at Oregon Health and Science University in Portland (ASCO abstract 106).

Michael J. Mauro, MD, and his colleagues reported that 58% of the patients responded to erythropoietic therapy with rises in hemoglobin counts of 2 g/dL or more. The study group also had treatment response rates in line with previous phase I and phase II trials of imatinib in CML patients. Among the chronic-phase patients treated with erythropoietic therapy, 44% had a major cytogenetic response, including 19% who had a complete cytogenetic response.

The 19 patients with accelerated-phase disease caused the most concern, according to Dr. Mauro. Yet these patients had the best responses to erythropoietin therapy (68%) and to imatinib. Nearly half (47%) achieved a major cytogenetic responses, including 37% who had a complete cytogenetic response. One of two patients with blast crisis responded to erythropoietic therapy, but neither responded to imatinib.

"The numbers are still fairly small, but it’s encouraging," Dr. Mauro told ONI, suggesting that erythropoietic therapy might allow advanced CML patients to receive more intensive therapy with imatinib, an ABL-tyrosine kinase inhibitor. At the time the patients received erythropoietic therapy, the mean dose of imatinib was 546 mg, reflecting the large proportion of accelerated-phase patients in the trial.

Anemia Is Common Problem

Anemia is a common problem for CML patients receiving imatinib, especially in the accelerated and blast phases of disease, according to Dr. Mauro. In previous trials, between 29% and 77% of these patients developed grade 3 or grade 4 anemia. Though the condition was nowhere as widespread in chronic-phase patients treated with imatinib, previous studies have also characterized anemia as a poor prognostic factor at any phase for any patient receiving imatinib therapy for CML.

Among the concerns about adding erythropoietin to imatinib was the possibility that the disease affects erythropoietic receptors. Another was the possibility that the growth factor would send growth or survival signals to malignant blood cells. Dr. Mauro and his coauthors theorized, however, that erythropoietic therapy would support nonmalignant erythropoiesis.

Grades 3 and 4 neutropenia and thrombocytopenia were common in all of the patients treated with erythropoietic therapy. Neutropenia was more common in responders to erythropoietic therapy, occurring in 67% of those responding to erythropoietic therapy and 59% of those who received the growth factors. Thrombocytopenia occurred in 70% of the study population.

The investigators concluded that erythropoietic therapy therapy is not only feasible during imatinib therapy but also might prevent interruptions to treatment and allow patients to receive higher doses of imatinib. Better supportive care, better quality of life, and less need for transfusion could also follow, they said and called for further investigation.