Current event-free survival after sequential tyrosine kinase inhibitor therapy for chronic myeloid leukemia

Abstract

Background: Imatinib is an effective tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML) in chronic phase (CP). Although some patients may fail on therapy with imatinib, effective salvage therapy is available with second-generation TKIs. Current measurement of efficacy for each therapy is judged by its individual impact on overall survival and event-free survival (EFS).

Methods: In total, 586 patients with CML in CP who received imatinib were included in this analysis in 2 cohorts: imatinib as front-line therapy (n = 281) or after failure on interferon-α (IFN-α) (n = 305). By accounting for successful salvage treatment (ie, regain of complete cytogenetic response), the current EFS (CEFS) rate was calculated to obtain a more accurate impression of the outcome of patients with CML who received treatment with sequential TKIs.

Results: For patients who received imatinib after failing on IFN-α, the 7-year EFS rate was 61%, whereas the CEFS rate was 69%. The 7-year EFS rate for patients who received imatinib as initial therapy was 81% compared with a 7-year CEFS rate of 88%.

Conclusions: CEFS provided a more accurate representation of the outcome of patients with CML in CP. These patients may frequently be treated successfully with subsequent TKIs after experiencing failure on the first TKI.

Figure 1

An algorithm for patients who received imatinib after failure on interferon-α failure is shown. CCyR indicates complete cytogenetic response; IM, imatinib; TKI, tyrosine kinase inhibitor; Rx, therapy; CR, complete response. Black boxes indicate events; a dagger indicates that, of 14 nonevents, 10 patients were lost to follow-up, 3 patients developed toxicity, and 1 patient developed other disease; an asterisk indicates the 4 patients categorized with “other diseases” had uterine cancer, pancreatic cancer, esophageal cancer, and myelodysplastic syndromes; a double dagger indicates that, of the 5 patients who maintained CCyR, 3 patients received dasatinib, 1 patient received bosutinib, and 1 patient received bafetinib (formerly known as INNO406); a section sign indicates that, of the 22 patients who received a second TKI, 6 patients received nilotinib, 11 patients received dasatinib, and 5 patients received bosutinib.

Figure 2

Event-free survival (EFS) and current EFS (CEFS) are illustrated for the patients who received imatinib after failure on interferon-α.

Figure 3

This is an algorithm for the patients who received imatinib as initial therapy. CCyR indicates complete cytogenetic response; IM, imatinib; FU, follow-up; TKI, tyrosine kinase inhibitor. Black boxes indicate events; a dagger indicates that 9 patients were lost to FU, 3 patients developed toxicity, and 3 patients were noncompliant; and an asterisk indicates that 1 patient developed acute myeloid leukemia, 2 patients required no further therapy, and 1 patient developed renal cell carcinoma.

Figure 4

Event-free survival (EFS) and current EFS (CEFS) are illustrated for the patients who received imatinib as their initial therapy.