Abstract

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).

Table 1

Number of patients in complete cytogenetic response at different time-points

 no of patients in CCgR, (%)
 
IM (419 patients) IM+IFN-alpha (76 patients) 
6 months 175 (42%) 46 (60%) 
12 months 284 (68%) 53 (70%) 
24 months 336 (80%) 62 (82%) 
36 months 342 (82%) 66 (87%) 
48 months 346 (82%) 62 (82%) 
 no of patients in CCgR, (%)
 
IM (419 patients) IM+IFN-alpha (76 patients) 
6 months 175 (42%) 46 (60%) 
12 months 284 (68%) 53 (70%) 
24 months 336 (80%) 62 (82%) 
36 months 342 (82%) 66 (87%) 
48 months 346 (82%) 62 (82%) 
Table 2

Percentage of patients in major molecular response (MMolR) evaluated on the entire study group.

 MMolR
 
p value 
IM (n.419) IM+PegIFN (n.76) 
6 months 34% 58% <0.0001 
12 months 46.5% 67% 0.001 
24 months 62% 64.5% 0.7 
36 months 58% 65% 0.52 
48 months 57% 65% 0.26 
 MMolR
 
p value 
IM (n.419) IM+PegIFN (n.76) 
6 months 34% 58% <0.0001 
12 months 46.5% 67% 0.001 
24 months 62% 64.5% 0.7 
36 months 58% 65% 0.52 
48 months 57% 65% 0.26 

These data support the preliminary analysis of the French SPIRIT group, reporting a higher rate of MMolR after initial treatment with IM and IFN-alpha as compared to IM alone. The loss of the difference from 24 mos on could be explained by the fact that almost all patients had discontinued IFN-alpha during the first two years, pointing out that the low compliance to the combination may limit its utility in practice. ACKNOWLEDGEMENT The Italian Association Against Leukemia-lymphoma and myeloma (BolognAIL), The Fondazione del Monte di Bologna e Ravenna, The Italian Ministery of Education (PRIN 2005, No. 20050 63732_003, and PRIN 2007, No 2007F7 AE7B_002), The University of Bologna, The European Union (European LeukemiaNet).

Disclosures:

Pane:Novartis: Research Funding; Ministero dell'Università/PRIN: Research Funding; Regione Campania: Research Funding; Ministero della Salute/Progetto integrato Oncologia: Research Funding. Saglio:Celgene: Honoraria; Novartis: Honoraria.

Author notes

*

Asterisk with author names denotes non-ASH members.