Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results

Hagop M Kantarjian, Francis J Giles, Kapil N Bhalla, Javier Pinilla-Ibarz, Richard A Larson, Norbert Gattermann, Oliver G Ottmann, Andreas Hochhaus, Jerald P Radich, Giuseppe Saglio, Timothy P Hughes, Giovanni Martinelli, Dong-Wook Kim, Yaping Shou, Neil J Gallagher, Rick Blakesley, Michele Baccarani, Jorge Cortes, Philipp D le Coutre, Hagop M Kantarjian, Francis J Giles, Kapil N Bhalla, Javier Pinilla-Ibarz, Richard A Larson, Norbert Gattermann, Oliver G Ottmann, Andreas Hochhaus, Jerald P Radich, Giuseppe Saglio, Timothy P Hughes, Giovanni Martinelli, Dong-Wook Kim, Yaping Shou, Neil J Gallagher, Rick Blakesley, Michele Baccarani, Jorge Cortes, Philipp D le Coutre

Abstract

Nilotinib is a potent selective inhibitor of the BCR-ABL tyrosine kinase approved for use in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP), and in CML-CP and CML-accelerated phase after imatinib failure. Nilotinib (400 mg twice daily) was approved on the basis of the initial results of this phase 2 open-label study. The primary study endpoint was the proportion of patients achieving major cytogenetic response (CyR). All patients were followed for ≥ 24 months or discontinued early. Of 321 patients, 124 (39%) continue on nilotinib treatment. Overall, 59% of patients achieved major CyR; this was complete CyR (CCyR) in 44%. Of patients achieving CCyR, 56% achieved major molecular response. CyRs were durable, with 84% of patients who achieved CCyR maintaining response at 24 months. The overall survival at 24 months was 87%. Adverse events were mostly mild to moderate, generally transient, and easily managed. This study indicates that nilotinib is effective, with a manageable safety profile, and can provide favorable long-term benefits for patients with CML-CP after imatinib failure.

Trial registration: ClinicalTrials.gov NCT00109707.

Figures

Figure 1
Figure 1
Major(MCyR) andcomplete cytogenetic response(CCyR)in patients with a minimum follow up of 24 months(N = 321).
Figure 2
Figure 2
Cytogenetic andmolecular responses in patients with and withoutCHR atbaseline (N = 321). CCyR indicates complete cytogenetic response; CHR, complete hematologic response; MCyR, major cytogenetic response; MMR, major molecular response (BCR-ABL ≤ 0.1% on the international scale). *n for MMR as follows: 294 patients for all, 105 with baseline CHR, and 189 without baseline CHR.
Figure 3
Figure 3
Kaplan-Meierestimate of progression-free survival (N = 321).
Figure 4
Figure 4
Kaplan-Meierestimate of event-free survival (N = 321).
Figure 5
Figure 5
Kaplan-Meierestimate of overall survival (N = 321).

Source: PubMed

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