Sustained Durability of Responses Plus High Rates of Cytogenetic Responses Result in Long-Term Benefit for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Treated with Imatinib (IM) Therapy: Update from the IRIS Study.

IM has proven to be superior to IFN+Ara-C for newly diagnosed pts with CML-CP (O’Brien et al, NEJM, 2003). At 30-months of follow-up, 79% of pts randomized to IM remain on IM with 83% of them now treated for > 24 months. Therefore, this analysis is focused on first-line IM pts (n=553). Evaluation included complete hematologic response (CHR), major/complete cytogenetic response (MCyR/CCyR), major molecular response (≥3 log reduction in BCR-ABL/BCR vs. pooled diagnostic samples) time to progression (TTP) - defined as loss of CHR/MCyR or evolution to accelerated phase/blast crisis [AP/BC] or death, time to AP/BC, and overall survival. Median follow-up for first-line IM pts is 31.1. Summary of results are the following:

The additional follow-up confirmed durable responses with first-line therapy while also demonstrating the effect of cytogenetic response on long-term outcomes. The estimated rate of confirmed responders remaining in response after achieving a CCyR at 30 months is >92%. Similarly, the estimated rate of patients still in response at 30 months after achieving either a MCyR or CHR is also >92% for both groups. Only 2% of pts with a confirmed loss of MCyR and 1% of the pts with a confirmed loss of CCyR subsequently progressed to AP/BC. Of these pts, 3 of 5 benefited from a dose increase to 600 or 800 mg of IM, while only 1 of 7 pts with a confirmed loss subsequently achieved a MCyR without a dose escalation.

A total of 75 pts received a marrow transplant (BMT) after discontinuation from the study; 30 in the IM arm (2 after crossover from IFN) and 45 pts who were randomized to IFN (21 after crossover to IM). There was no difference in survival after BMT between pts who received first-line IM treatment (8 deaths, 1 after crossover) and pts who had received IFN+Ara–C (7 deaths) or IFN+Ara–C followed by IM (7 deaths) (p=0.78). The estimated survival at 12 months after BMT is 70%, 75%, and 68% respectively in the three groups.

A landmark analysis showed that for 407 pts who achieved MCyR within 6 months, their estimated rate free of AP/BC at 30 months is 97% vs. 89% for the 124 pts who did not achieve this level of response at 6 months (p<0.001). Additionally, the estimated survival at 30 months for the same pts is 97% vs. 92% (p=0.0162).

The achievement of a major molecular response at 12 months was also associated with improved progression-free survival. For patients who had achieved CCyR and a reduction in BCR-ABL transcript level ≥ 3 log at 12 months, the probability of remaining progression free was 100% at 30 months compared to 93% for such patients with reduction in BCR-ABL transcript level < 3 log and 82% for patients who were not in CCyR at 12 months (p<0.0001).

These results will be further updated using a data cut-off of 31-July-04 to reflect additional 12-months of data (i.e., 42-month follow-up).