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Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study |
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| Authors: | Michele Baccarani Brian J. Druker Susan Branford Dong-Wook Kim Fabrizio Pane Lidia Mongay Manisha Mone Christine-Elke Ortmann Hagop M. Kantarjian Jerald P. Radich Timothy P. Hughes Jorge E. Cortes François Guilhot |
| Affiliation: | 1. Department of Hematology and Oncology “L. e A. Seràgnoli,” S.Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy 2. Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA 3. Centre for Cancer Biology, SA Pathology, University of Adelaide, Adelaide, Australia 4. Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea 5. University of Naples Federico II, Naples, Italy 6. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA 7. Novartis Pharma AG, Basel, Switzerland 8. The University of Texas, MD Anderson Cancer Center, Houston, TX, USA 9. Fred Hutchinson Cancer Research Center, Seattle, WA, USA 10. Division of Haematology and Centre for Cancer Biology, SA Pathology, South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia 11. Inserm CIC 1402, CHU de Poitiers, Poitiers, France |
| Abstract: | The TOPS trial evaluated high- (800 mg/day; n = 319) versus standard-dose (400 mg/day; n = 157) imatinib in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Patients had a minimum follow-up of 42 months or discontinued early. Major molecular response (MMR) rates were similar between arms at (51.6 vs 50.2 % for 400 and 800 mg/day, respectively; P = 0.77) and by (75.8 vs 79.0 %; P = 0.4807) 42 months. There were no differences in event-free survival (EFS), progression-free survival (PFS), or overall survival (OS) between arms. The estimated rates of PFS on treatment and OS at 42 months were significantly higher in patients with MMR at 6, 12, and 18 months compared with those without MMR. Adverse events were more frequent with high-dose imatinib. Patients with ≤1 treatment interruption (vs >1) and those able to maintain imatinib ≥600 mg/day (vs <600 mg/day) in the first year of treatment had faster and higher response rates, but no improvement in EFS or PFS. Adherence to prescribed dose without interruption may be more important than initiation of therapy with higher doses of imatinib. Achievement of MMR correlated with long-term clinical outcomes. |
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