Skip to main content
Top
Published in: Annals of Hematology 1/2017

01-01-2017 | Original Article

Imatinib dose reduction in patients with chronic myeloid leukemia in sustained deep molecular response

Authors: Francisco Cervantes, Juan-Gonzalo Correa, Isabel Pérez, Valentín García-Gutiérrez, Sara Redondo, Dolors Colomer, Antonio Jiménez-Velasco, Juan-Luis Steegmann, Fermín Sánchez-Guijo, Francisca Ferrer-Marín, Arturo Pereira, Santiago Osorio, on behalf of the CML Spanish Group (GELMC)

Published in: Annals of Hematology | Issue 1/2017

Login to get access

Abstract

To determine whether a lower imatinib dose could minimize toxicity while maintaining the molecular response (MR), imatinib dose was reduced to 300 mg daily in 43 patients with chronic myeloid leukemia (CML) in sustained deep molecular response to first-line imatinib 400 mg daily. At the time of dose reduction, median duration of the deep response was 4.1 (interquartile range (IQR) 2.2–5.9) years; molecular response was MR4, MR4.5, and MR5 of the international scale in 6, 28, and 9 patients, respectively. Toxicity grade was 1, 2, and 3 in 28, 8, and 1 patients, respectively; 6 patients underwent dose reduction without having side effects. With a median of 1.6 (IQR 0.7–3.2) years on imatinib 300 mg daily, only one patient lost the deep molecular response to MR3. At the last follow-up, response was MR3, MR4, MR4.5, and MR5 in 1, 3, 9, and 30 patients, respectively. Toxicity improvement was observed in 23 (62.2 %) of the 37 patients with side effects, decreasing to grade 0 in 20 of them. All but one anemic patients improved (p = 0.01), the median Hb increase in this subgroup of patients being 1 g/dL. In CML patients with sustained deep response to the standard imatinib dose, reducing to 300 mg daily significantly improves tolerability and preserves efficacy.
Literature
1.
go back to reference Druker BJ, Guilhot F, O’Brien SG et al (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355:2408–2417CrossRefPubMed Druker BJ, Guilhot F, O’Brien SG et al (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355:2408–2417CrossRefPubMed
2.
go back to reference Deininger M, O’Brien SG, Guilhot F et al (2009) International randomized study of interferon vs STI571 (IRIS) 8-year follow-up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Blood 114:1126 (abstract) Deininger M, O’Brien SG, Guilhot F et al (2009) International randomized study of interferon vs STI571 (IRIS) 8-year follow-up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Blood 114:1126 (abstract)
3.
go back to reference Pfirrmann M, Baccarani M, Saussele S et al (2016) Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia. Leukemia 30:48–56CrossRefPubMed Pfirrmann M, Baccarani M, Saussele S et al (2016) Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia. Leukemia 30:48–56CrossRefPubMed
4.
go back to reference Hochhaus A, Saglio G, Hughes TP et al (2016) Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia 30:1044–1054CrossRefPubMedPubMedCentral Hochhaus A, Saglio G, Hughes TP et al (2016) Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia 30:1044–1054CrossRefPubMedPubMedCentral
5.
go back to reference Jabbour E, Kantarjian HM, Saglio G et al (2014) Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood 123:494–500CrossRefPubMedPubMedCentral Jabbour E, Kantarjian HM, Saglio G et al (2014) Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood 123:494–500CrossRefPubMedPubMedCentral
6.
go back to reference De Lavallade H, Apperley JF, Khorashad JS et al (2008) Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol 26:3358–3363CrossRefPubMed De Lavallade H, Apperley JF, Khorashad JS et al (2008) Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol 26:3358–3363CrossRefPubMed
7.
go back to reference Cervantes F, López-Garrido P, Montero MI et al (2010) Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group. Haematologica 95:1317–1324CrossRefPubMedPubMedCentral Cervantes F, López-Garrido P, Montero MI et al (2010) Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group. Haematologica 95:1317–1324CrossRefPubMedPubMedCentral
8.
go back to reference Efficace F, Baccarani M, Breccia M et al (2013) Chronic fatigue is the most important factor limiting health-related quality of life of chronic myeloid leukemia patients treated with imatinib. Leukemia 27:1511–1519CrossRefPubMed Efficace F, Baccarani M, Breccia M et al (2013) Chronic fatigue is the most important factor limiting health-related quality of life of chronic myeloid leukemia patients treated with imatinib. Leukemia 27:1511–1519CrossRefPubMed
9.
go back to reference Guérin A, Chen L, Ionescu-Ittu R, Marynchenko M, Nitulescu R, Hiscock R, Keir C, Wu EQ (2014) Impact of low-grade adverse events on health-related quality of life in adult patients receiving imatinib or nilotinib for newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase. Curr Med Res Opinion 30:2317–2328CrossRef Guérin A, Chen L, Ionescu-Ittu R, Marynchenko M, Nitulescu R, Hiscock R, Keir C, Wu EQ (2014) Impact of low-grade adverse events on health-related quality of life in adult patients receiving imatinib or nilotinib for newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase. Curr Med Res Opinion 30:2317–2328CrossRef
10.
go back to reference Flynn KE, Atallah E (2016) Quality of life and long-term therapy in patients with chronic myeloid leukemia. Curr Hem Malign Rep 11:80–85CrossRef Flynn KE, Atallah E (2016) Quality of life and long-term therapy in patients with chronic myeloid leukemia. Curr Hem Malign Rep 11:80–85CrossRef
11.
go back to reference Hughes TP, Lipton JH, Spector N et al (2014) Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after long-term imatinib. Blood 124:729–736CrossRefPubMed Hughes TP, Lipton JH, Spector N et al (2014) Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after long-term imatinib. Blood 124:729–736CrossRefPubMed
12.
go back to reference Hochhaus A, Baccarani M, Deininger M et al (2008) Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia 22:1200–1206CrossRefPubMed Hochhaus A, Baccarani M, Deininger M et al (2008) Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia 22:1200–1206CrossRefPubMed
13.
go back to reference Gambacorti-Passerini C, Brümmendorf TH, Kim DW et al (2014) Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: minimum 24-month follow-up. Am J Hematol 89:732–742CrossRefPubMedPubMedCentral Gambacorti-Passerini C, Brümmendorf TH, Kim DW et al (2014) Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: minimum 24-month follow-up. Am J Hematol 89:732–742CrossRefPubMedPubMedCentral
14.
go back to reference Faber E, Divoká M, Skoumalová I, Novák M, Marešová I, Mičová K, Friedecký D, Adam T, Jarošová M, Indrák K (2015) A lower dosage of imatinib is sufficient to maintain undetectable disease in patients with chronic myeloid leukemia with long-term low-grade toxicity of the treatment. Leuk & Lymph 57:1–6 Faber E, Divoká M, Skoumalová I, Novák M, Marešová I, Mičová K, Friedecký D, Adam T, Jarošová M, Indrák K (2015) A lower dosage of imatinib is sufficient to maintain undetectable disease in patients with chronic myeloid leukemia with long-term low-grade toxicity of the treatment. Leuk & Lymph 57:1–6
15.
go back to reference Cross NCP, White HE, Colomer D et al (2015) Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia. Leukemia 29:999–1003CrossRefPubMedPubMedCentral Cross NCP, White HE, Colomer D et al (2015) Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia. Leukemia 29:999–1003CrossRefPubMedPubMedCentral
16.
go back to reference Mahon FX, Réa D, Guilhot J et al (2010) Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 11:1029–1035CrossRefPubMed Mahon FX, Réa D, Guilhot J et al (2010) Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 11:1029–1035CrossRefPubMed
17.
go back to reference Ross DM, Branford S, Seymour JF et al (2013) Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood 122:515–522CrossRefPubMed Ross DM, Branford S, Seymour JF et al (2013) Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood 122:515–522CrossRefPubMed
18.
19.
go back to reference Saussele S, Richter J, Guilhot J et al (2014) First interim analysis of a pan-European stop trial using standardized molecular criteria: results of the EURO-SKI trial. Haematologica 99:792 (abstract) Saussele S, Richter J, Guilhot J et al (2014) First interim analysis of a pan-European stop trial using standardized molecular criteria: results of the EURO-SKI trial. Haematologica 99:792 (abstract)
20.
go back to reference Russo D, Martinelli G, Malagola M et al (2013) Effects and outcome of a policy of intermittent imatinib treatment in elderly patients with chronic myeloid leukemia. Blood 121:5138–5144CrossRefPubMed Russo D, Martinelli G, Malagola M et al (2013) Effects and outcome of a policy of intermittent imatinib treatment in elderly patients with chronic myeloid leukemia. Blood 121:5138–5144CrossRefPubMed
21.
go back to reference Guilhot F, Druker B, Larson RA, Gathmann I, So C, Waltzman R, O’Brien SG (2009) High rates of durable response are achieved with imatinib after treatment with interferon alpha plus cytarabine: results from the International Randomized Study of Interferon and STI571 (IRIS) trial. Haematologica 94:1669–1675CrossRefPubMedPubMedCentral Guilhot F, Druker B, Larson RA, Gathmann I, So C, Waltzman R, O’Brien SG (2009) High rates of durable response are achieved with imatinib after treatment with interferon alpha plus cytarabine: results from the International Randomized Study of Interferon and STI571 (IRIS) trial. Haematologica 94:1669–1675CrossRefPubMedPubMedCentral
Metadata
Title
Imatinib dose reduction in patients with chronic myeloid leukemia in sustained deep molecular response
Authors
Francisco Cervantes
Juan-Gonzalo Correa
Isabel Pérez
Valentín García-Gutiérrez
Sara Redondo
Dolors Colomer
Antonio Jiménez-Velasco
Juan-Luis Steegmann
Fermín Sánchez-Guijo
Francisca Ferrer-Marín
Arturo Pereira
Santiago Osorio
on behalf of the CML Spanish Group (GELMC)
Publication date
01-01-2017
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 1/2017
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-016-2839-z

Other articles of this Issue 1/2017

Annals of Hematology 1/2017 Go to the issue