Continuing Reduction in Level of Residual Disease after 4 Years in Patients with CML in Chronic Phase Responding to First-Line Imatinib (IM) in the IRIS Study.

Background and methods: The IRIS study initiated in June 2000 compared treating newly diagnosed CML-CP pts with IM or interferon+ara-C. Pts who achieved a complete cytogenetic response (CCyR) had BCR-ABL transcript numbers in the blood measured serially by real-time quantitative PCR. Results were expressed as a log reduction from a standardized baseline value for untreated pts. We showed previously that by 1 year an estimated 40% of pts who started IM at 400 mg/day had achieved a major molecular response (MMR) defined as ≥3 log reduction in BCR-ABL levels. Of the 136 pts who achieved MMR at one year, all survived at 42 months without evidence of progression to advanced phase whereas 5% of the 94 pts who failed to achieve MMR at one year had progressed. Although routine PCR sampling was interrupted January 2003, (24 months after end of study recruitment), 6-monthly monitoring was resumed in August 2004 for all pts on study regardless of CCyR status. PCR data analyzed up to February 2005 are included here.

Objectives: To evaluate level of BCR-ABL transcripts after approximately 4 years on IM in pts who had transcript numbers measured in CCyR at 1 year. Of the 553 pts who started treatment with IM, this analysis is based on the 101 pts who had achieved CCyR within 1 year, who received first-line treatment at least for 24 months and who had blood collected for measuring transcript numbers at 1 year and 4 years after starting treatment.

Results: At 1 year BCR-ABL transcript levels had fallen by at least 3 log in 47 (46%) of the 101 pts. At the most recent measurement at or after 44 months from start of study (median 49 months, range 44 – 55), 76 (75%) pts showed a reduction of at least 3 logs. Of these 76 pts, 39 (51%) had already had a ≥3 log reduction at year one, whereas 37 (49%) had not. Conversely 8 of the 47 pts with ≥3 log reduction at 1 year had log reductions <3 at 4 years (see table).

Table 1.

BCR-ABL log reduction

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For all pts the mean ± SD log reduction was 3.0 ± 1.0 at 1 year and 3.4 ± 1.1 at 4 years (p=0.0008, paired t-test). At the 1 and 4 year points 20 (20%) and 36 (36%) respectively of these pts had achieved ≥4 log reductions. In this subset responding well to IM, the majority of pts have BCR-ABL transcript levels that continue to decline with 35% falling more than 1 log and 18% falling 0.5–1 log between 1 and 4 years; however in 13% levels increased more than 1 log between the two time-points.

Summary:. Pts with CCyR and a moderate decline of their BCR-ABL transcript levels at 1 year still have a good chance of achieving an MMR at 4 years. The full analysis (data cut-off of 31-July-2005) will be presented together with the relationship of transcript levels to clinical outcomes.