Researchers affiliated with the IRIS study comparing interferon to Gleevec® as initial therapy for patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase have reported continuing success with Gleevec® therapy after 42 months of follow-up. The results of this analysis were reported at the 2004 meeting of the American Society of Hematology in San Diego December 4-7.

The IRIS study was a randomized comparison of Gleevec® versus alfa interferon and cytarabine for the initial therapy of CML. There were 177 centers in 16 countries involved in this study. A total of 553 patients were randomly allocated to each arm of this study. There was a cross-over, which allowed failures on one arm to receive the treatment of the alternate arm. At 42 months, 75% of Gleevec® patients remain on study, compared to 4% of the interferon group. Initial results showed a 98% hematological CR rate, a major cytogenetic response in 91% and a cytogenetic CR in 84% following Gleevec® therapy. Using the Sokol criteria, the cytogenetic CR rate was 91% for low-risk patients, 84% for intermediate risk patients and 69% for high risk patients, showing that this classification system is still valid. At the 42 month follow-up, the PFS was 84% and the OS was 94%. Table 1 shows the rates of disease progression for each of the 4 years of follow up.

Table 1: Rate of disease progression following Gleevec® therapy

Progressive disease was related to the degree of response as determined by cytogenetics and PCR analysis. Patients with a cytogenetic CR had a progression rate of 8% while those with<3 log reduction on PCR had a 2% progression. Those with lesser responses had higher rates of disease progression. Since this was a crossover study, survival differences were minimal, with a 97% OS for initial Gleevec® therapy and 94% for salvage Gleevec® therapy.

In the abstract, these authors reported that 30 patients in the Gleevec® arm and 45 in the interferon arm ultimately received stem cell transplants. There were essentially 3 groups of patients: those who received first-line therapy with Gleevec® had a 70% survival; those who received interferon had a survival of 75%; and those who received interferon followed by Gleevec® had a survival of 68%.

Comments: These are very interesting data and indicate that patients who achieve a cytogenetic CR with >3log reduction in PCR have a very low rate of progression after 42 months. Importantly, there was no evidence that the rate of progression in any group increased with time. The preliminary data on stem cell transplants is also important, as it suggests that prior Gleevec® does not compromise survival.

Reference: Guihot F. On behalf of the IRIS (International Randomized IFN vs STI571) Study Group. 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. Proceedings of the American Society of Hematology. Blood. 2004;104:10a, abstract number 21.