BACKGROUND: Imatinib mesylate given orally at a daily dose of 400 mg is the standard of care as initial therapy for patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP). Treatment guidelines propose dose escalation based on clinical assessments of disease response. METHODS: Response and survival were analyzed in a cohort of patients (n = 106) with newly diagnosed CML-CP who were enrolled on the International Randomized Study of Interferon and STI571 (IRIS) trial, who began treatment with imatinib at a dose of 400 mg daily, and who subsequently underwent dose escalation to either 600 mg or 800 mg daily. Reasons for dose escalation were evaluated retrospectively based on 2 sets of criteria: the IRIS protocol-defined criteria (n = 39 patients) and the European LeukemiaNet (ELN) recommendations (n = 48 patients). RESULTS: Among all 106 patients who underwent dose escalation, the rates of freedom from progression to accelerated phase or blast phase and overall survival were 89% and 84% at 3 years after dose increase, respectively. A cytogenetic response was obtained in 42% of patients who had their dose escalated based on protocol criteria and in 38% of patients who had their dose escalated according to the ELN recommendations. CONCLUSIONS: The results from this retrospective analysis supported imatinib dose escalation as an appropriate initial option for patients with CML-CP who were experiencing suboptimal cytogenetic response or resistance.
Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase / Kantarjian HM; Larson RA; Guilhot F; O'Brien SG; Mone M; Rudoltz M; Krahnke T; Cortes J; Druker BJ; International Randomized Study of Interferon and STI571 (IRIS) Investigators. Durant S; Schwarer A; Joske D; Seymour J; Grigg A; Ma D; Arthur C; Bradstock K; Joshua D; Louwagi A; Martiat P; Bosly A; Shistok C; Lipton J; Forrest D; Walker I; Roy DC; Rubinger M; Bence-Bruckler I; Stewart D; Kovacs M; Turner AR; Birgens H; Bjerrum O; Facon T; Harousseau JL; Tulliez M; Guerci A; Blaise D; Maloisel F; Michallet M; Andreesen R; Nerl C; Freund M; Gattermann N; Ehninger G; Deininger M; Ottmann O; Peschel C; Fruehauf S; Neubauer A; le Coutre P; Aulitzky W; Fanin R; Rosti G; Mandelli F; Lazzarino M; Morra E; Carella A; Petrini M; Nobile F; Liso V; Ferrara F; Rizzoli V; Fiortoni G; Martinelli G; Ossenkoppele G; Browett P; Gedde-Dahl T; Tangen JM; Dahl I; Odrizoala J; Hernandez Boulda JC; Steegman JL; Canizo C; Diaz J; Grenena A; Fernandez MN; Stenke L; Paul C; Bjoreman M; Malm C; Wadenvik H; Nilsson PG; Turesson I; Hess U; Solenthaler M; Clark RE; Green AR; Holyoake TL; Lucas GS; Smith G; Milligan DW; Rule SJ; Burnett AK; Moroose R; Wetzler M; Bearden J; Cataland S; Robinowitz I; Meisenberg B; Thompson K; Graziano S; Emanuel P; Gross H; Cobb P; Bhatia R; Dakhil S; Irwin D; Issell B; Pavletic S; Kuebler P; Layhe E; Butra P; Glass J; Moore J; Grant B; Neill H; Herzig R; Burris H; Petersen B; Kalaycio M; Stirewalt D; Samlowski W; Berman E; Limentani S; Seay T; Shea T; Akard L; Smith G; Becker P; Devine S; Hart R; Veith R; Wade J; Brunvad M; Kalman L; Strickland D; Shurafa M; Bashey A; Shadduck R; Safah H; Rubenstein M; Collins R; Keller A; Tallman M; Pecora A; Agha M; Homes H; Guidice R; Santini V. Kantarjian HM; Larson RA; Guilhot F; O'Brien SG; Mone M; Rudoltz M; Krahnke T; Cortes J; Druker BJ; International Randomized Study of Interferon and STI571 (IRIS) Investigators. Durant S; Schwarer A; Joske D; Seymour J; Grigg A; Ma D; Arthur C; Bradstock K; Joshua D; Louwagi A; Martiat P; Bosly A; Shistok C; Lipton J; Forrest D; Walker I; Roy DC; Rubinger M; Bence-Bruckler I; Stewart D; Kovacs M; Turner AR; Birgens H; Bjerrum O; Facon T; Harousseau JL; Tulliez M; Guerci A; Blaise D; Maloisel F; Michallet M; Andreesen R; Nerl C; Freund M; Gattermann N; Ehninger G; Deininger M; Ottmann O; Peschel C; Fruehauf S; Neubauer A; le Coutre P; Aulitzky W; Fanin R; Rosti G; Mandelli F; Lazzarino M; Morra E; Carella A; Petrini M; Nobile F; Liso V; Ferrara F; Rizzoli V; Fiortoni G; Martinelli G; Ossenkoppele G; Browett P; Gedde-Dahl T; Tangen JM; Dahl I; Odrizoala J; Hernandez Boulda JC; Steegman JL; Canizo C; Diaz J; Grenena A; Fernandez MN; Stenke L; Paul C; Bjoreman M; Malm C; Wadenvik H; Nilsson PG; Turesson I; Hess U; Solenthaler M; Clark RE; Green AR; Holyoake TL; Lucas GS; Smith G; Milligan DW; Rule SJ; Burnett AK; Moroose R; Wetzler M; Bearden J; Cataland S; Robinowitz I; Meisenberg B; Thompson K; Graziano S; Emanuel P; Gross H; Cobb P; Bhatia R; Dakhil S; Irwin D; Issell B; Pavletic S; Kuebler P; Layhe E; Butra P; Glass J; Moore J; Grant B; Neill H; Herzig R; Burris H; Petersen B; Kalaycio M; Stirewalt D; Samlowski W; Berman E; Limentani S; Seay T; Shea T; Akard L; Smith G; Becker P; Devine S; Hart R; Veith R; Wade J; Brunvad M; Kalman L; Strickland D; Shurafa M; Bashey A; Shadduck R; Safah H; Rubenstein M; Collins R; Keller A; Tallman M; Pecora A; Agha M; Homes H; Guidice R; Santini V.. - In: CANCER. - ISSN 0008-543X. - STAMPA. - 115:(2009), pp. 551-560. [10.1002/cncr.24066]
Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase.
SANTINI, VALERIA
2009
Abstract
BACKGROUND: Imatinib mesylate given orally at a daily dose of 400 mg is the standard of care as initial therapy for patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP). Treatment guidelines propose dose escalation based on clinical assessments of disease response. METHODS: Response and survival were analyzed in a cohort of patients (n = 106) with newly diagnosed CML-CP who were enrolled on the International Randomized Study of Interferon and STI571 (IRIS) trial, who began treatment with imatinib at a dose of 400 mg daily, and who subsequently underwent dose escalation to either 600 mg or 800 mg daily. Reasons for dose escalation were evaluated retrospectively based on 2 sets of criteria: the IRIS protocol-defined criteria (n = 39 patients) and the European LeukemiaNet (ELN) recommendations (n = 48 patients). RESULTS: Among all 106 patients who underwent dose escalation, the rates of freedom from progression to accelerated phase or blast phase and overall survival were 89% and 84% at 3 years after dose increase, respectively. A cytogenetic response was obtained in 42% of patients who had their dose escalated based on protocol criteria and in 38% of patients who had their dose escalated according to the ELN recommendations. CONCLUSIONS: The results from this retrospective analysis supported imatinib dose escalation as an appropriate initial option for patients with CML-CP who were experiencing suboptimal cytogenetic response or resistance.
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