The Combination of Interferon-Alpha with Imatinib in Early Chronic Phase Chronic Myeloid Leukemia Patients Induces a Significant Improvement of the Molecular Responses in the First Two Years of Treatment: Results From Three Studies From the GIMEMA CML Working Party.

Abstract 2192

Poster Board II-169

Thanks to its striking effectiveness, imatinib (IM) is the current standard of therapy in chronic myeloid leukemia (CML). However, Interferon-alpha (IFN-alpha) has induced a low but reproducible curative effect in some CML patients, inducing durable remissions lasting even after therapy discontinuation. For this reason, the interest on the possible use of IFN-alpha in the treatment of CML is still substantial, and very recently some newer prospective studies from the French and the German Groups have proposed the re-introduction of IFN-alpha in the front-line treatment of early chronic phase CML (ECP-CML), in association with IM (Rousselot et al, Haematologica 2009;94:abs.1093; Hehlmann et al, Haematologica 2009;94:abs. 0478). We compared the response of 495 ECP-CML patients, enrolled into three different prospective studies promoted by the GIMEMA CML WP (419 treated with imatinib 400mg and 76 treated with imatinib 400mg plus IFN-alpha) (study protocols NCT00511121, NCT00514488 and NCT00511303). Cytogenetic analysis was performed by standard banding techniques and cytogenetic response was rated according to the European LeukemiaNet guidelines. Molecular response was assessed on peripheral blood cells by a standardized quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) method on an ABI PRISM 7700 Sequence Detector (Perkin Elmer, Faster City, CA). BCR-ABL transcript levels were expressed as a percentage according to the IS.

Patients were equally distributed by Sokal risk in the two cohorts. Median follow-up was 43 mos (range, 12- 67) in the IM group and 54 mos (range, 11-63) in the IM+IFN-alpha group. Compliance to IM was excellent in both groups, with 90 to 95% of patients receiving IM 400 mg/daily throughout the follow-up. Conversely, the proportion of patients continuing IFN-alpha dropped from 41% at 12 mos to 18% at 18 mos, 13% at 24 mos, 3% at 36 mos; by the end of the fourth year, all patients were off IFN-alpha.

The number of patients in CCgR was higher in the IM+IFN-alpha than in the IM group at 6 mos (60% vs 42%, p=0.002) but not from 12 mos on (Table 1). The number of patients in MMolR was higher in the IM+IFN-alpha than in the IM group at 6, 12 and 24 mos, but not later on (Table 2). Also the number of patients with undetectable Bcr-Abl transcript levels was higher in the IM+IFN-alpha group at 12 months (15% vs 5%, p=0.003) but not later on (19% vs 18% at 48 mos).