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Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia. A study of the Spanish PETHEMA group

¹ Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
² Hospital Ruiz de Alda, Granada, Spain
³ Hospital Virgen del Rocío, Seville, Spain
⁴ Hospital Central de Asturias, Oviedo, Spain
⁵ Hospital Universitario La Fe, Valencia, Spain
⁶ Hospital Clínico, Valencia, Spain
⁷ Hospital Ramón y Cajal, Madrid, Spain
⁸ Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
⁹ Hospital Gregorio Marañón, Madrid, Spain
¹⁰ Hospital Morales Masaguer, Murcia, Spain
¹¹ Hospital Clínico de San Carlos, Madrid, Spain
¹² Hospital Reina Sofía, Córdoba, Spain
¹³ Hospital Clínico Universitario, Salamanca, Spain

Correspondence: Francisco Cervantes, MD, Hematology Department, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. Phone: international +34.932275428. Fax: international +34.932275484. E-mail: fcervan{at}clinic.ub.es

ABSTRACT

Background: Despite the favorable results of imatinib frontline in chronic-phase chronic myeloid leukemia (CP-CML), there is room for improvement.

Design and Methods: Early intervention during imatinib therapy was undertaken in 210 adults with CP-CML <3 months from diagnosis (Sokal high risk: 16%). Patients received imatinib 400 mg/day. At 3 months, dose was increased if complete hematologic response (CHR) was not achieved. At 6 months, patients in complete cytogenetic response (CCyR) were kept on 400 mg and the remainder randomized to higher imatinib dose or 400 mg plus interferon-alfa (IFN). At 18 months, randomized patients were switched to a second-generation tyrosine kinase inhibitor if not in CCyR and imatinib dose increased in non-randomized patients not in major molecular response (MMolR).

Results: 72% of patients started imatinib within one month from diagnosis. Median follow-up is 50.5 (range: 1.2–78) months. At 3 months, 4 patients had not CHR; at 6 months, 73.8% were in CCyR; among the remainder, 9 could not be randomized (toxicity or consent withdrawal), 17 were assigned high imatinib dose, and 15 to 400 mg + IFN. The low number of randomized patients precluded comparison between the two arms. Cumulative response 3 years was: CHR 98.6 %, CCyR 90%, and MMolR 82%. On an intention-to-treat basis, CCyR was 78.8% at 18 months. At 5 years, survival was 97.5%, survival free from accelerated/blastic phase 94.3%, failure-free survival 82.5%, and event-free survival (including permanent imatinib discontinuation) 71.5%.

Conclusions: These results indicate the benefit of early intervention during imatinib therapy.

Key words: chronic myeloid leukemia, treatment, imatinib.