Chronic myeloid leukemia and interferon-α: a study of complete cytogenetic responders

Abstract

Achieving a complete cytogenetic response (CCgR) is a major target in the treatment of chronic myeloid leukemia (CML) with interferon-␣ (IFN-␣), but CCgRs are rare. The mean CCgR rate is 13%, in a range of 5% to 33%. A collaborative study of 9 European Union countries has led to the collection of data on 317 patients who were first seen between 1983 and 1997 and achieved CCgRs with IFN-␣ alone or in combination with hydroxyurea. The median time to first CCgR was 19 months (95% CI, 17-21; range, 3-84 months). At last contact, 212 patients were still alive and in continuous CCgR; 105 patients had lost CCgR, but 53% of them were still alive and in chronic phase. IFN-␣ treatment was discontinued permanently in 23 cases for response loss, in 36 cases for chronic toxicity (15 are still in unmaintained continuous CCgR), and in 8 cases because it was believed that treatment was no longer necessary (7 of these 8 patients are still in unmaintained continuous CCgR). The 10-year survival rate from first CCgR is 72% (95% CI, 62%-82%) and is related to the risk profile. High-risk patients lost CCgR more frequently and more rapidly and none survived more than 10 years. Low-risk patients survived much longer (10-year survival probability 89% for Sokal low risk and 81% for Euro low risk). These data point out that a substantial long-term survival in CCgRs is restricted mainly to low-risk and possibly intermediate-risk patients and occurs significantly less often in high-risk patients. (Blood. 2001;98:3074-3081)

Efficacy and safety of imatinib in patients with chronic myeloid leukemia and complete or near‐complete cytogenetic response to interferon‐α

“…For those who achieved a CCR, the 10-year survival rate was 72% (95% confidence interval [95% CI], 62-82%), and was found to be correlated with the risk profile. 16 Patients who commenced IFNa with a high risk and achieved a CCR had significantly shorter survival. In contrast, for first-line imatinib-treated patients with CCR there was no significant difference in the overall survival noted between the Sokal risk groups after 60 months of imatinib treatment.…”

“…Unfortunately, even patients with good responses to IFN-a show a slow rate of recurrence and progression of their disease, despite ongoing IFN-a treatment. 16,30 The main requirement for a prolonged survival while receiving IFN-a treatment was achieving and maintaining a CCR. 16 In our study, 8 of the 23 patients had not achieved a CCR at 1.6 to 4.6 years after commencing IFN-a treatment.…”

Standardized definitions of molecular response in chronic myeloid leukemia

“…[22][23][24] Recent data from a proof of concept study of TKI cessation (with IFN maintenance) following MMR on imatinib plus IFN demonstrated promising results. 25 In this study, imatinib therapy was stopped in 20 patients who had concomitantly been pretreated with imatinib and IFN for over 2 years.…”

Molecular monitoring to improve outcomes in patients with chronic myeloid leukemia in chronic phase: Importance of achieving treatment‐free remission

“…A potential theoretical concern is the possibility of patients developing advanced-phase CML during TFR without warning; however, abrupt progression to AP or BC has not been seen in the small groups of patients off therapy in the trials summarized here. Of note, cases of transformation to advanced disease have been described in patients following IFN cessation [41,42,56].…”