The online version of this article (doi:10.1186/1752-1947-8-295) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
All authors analyzed and interpreted the patient data and wrote the manuscript. All authors read and approved the final manuscript.
Although there is a considerable amount of data in the literature on safe discontinuation of first-generation tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia, little is known about discontinuation of second-generation tyrosine kinase inhibitor therapy. Most previous studies have been focused on dasatinib, and the few cases of nilotinib withdrawal that have been reported had a median follow-up of 12 months. To the best of our knowledge, the present report is the first to describe nilotinib withdrawal with 30 months of follow-up.
We report the case of a 64-year-old Caucasian man diagnosed with chronic-phase chronic myeloid leukemia in April 2005. After 4 years of treatment with imatinib, he became intolerant to the drug and was switched to nilotinib. Two years later, he decided to stop nilotinib. Undetectable molecular response persisted for 30 months after discontinuation of the drug.
Our present case suggests that nilotinib withdrawal is safe for patients with chronic myeloid leukemia who achieve a stable undetectable molecular response. Our patient was homozygous for killer immunoglobulin-like receptor haplotype A, previously reported to be a promising immunogenetic marker for undetectable molecular response. We recommend additional studies to investigate patient immunogenetic profiles and their potential role in complete response to therapy.
Authors’ original file for figure 113256_2014_2917_MOESM1_ESM.tif
Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini A, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Martinelli G, Mayer J, Müller MC, Niederwieser D, Pane F, Radich JP, Rousselot P, Saglio G, Sauβele S, Schiffer C, Silver R, Simonsson B, Steegmann JL: European LeukemiaNet recommendations for the management of chronic myeloid leukemia. Blood. 2013, 122: 872-884. 10.1182/blood-2013-05-501569. CrossRefPubMed
Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B, Etienne G, Reiffers J, Rousselot P, Intergroupe Français des Leucémies Myéloïdes Chroniques: Discontinuation of imatinib in patients with chronic myeloid leukemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010, 11: 1029-1035. 10.1016/S1470-2045(10)70233-3. CrossRefPubMed
Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Yeung DT, Dang P, Goyne JM, Slader C, Filshie RJ, Mills AK, Melo JV, White DL, Grigg AP, Hughes TP: Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER Study. Blood. 2013, 122: 515-522. 10.1182/blood-2013-02-483750. CrossRefPubMed
Benjamini O, Kantarjian H, Rios MB, Jabbour E, O’Brien S, Jain P, Cardenas-Turanzas M, Faderl S, Garcia-Manero G, Ravandi F, Borthakur G, Quintas-Cardama A, Cortes J: Patient-driven discontinuation of tyrosine kinase inhibitors: single institution experience. Leuk Lymphoma in press. doi:10.3109/10428194.2013.831092
Rea D, Rousselot P, Guilhot F, Tulliez M, Nicolini FE, Guerci-Bresler A, Legros L, Gardembas M, Giraudier S, Guillerm G, Mahon FX: Discontinuation of second generation (2G) tyrosine kinase inhibitors (TKI) in chronic phase (CP)-chronic myeloid leukemia (CML) patients with stable undetectable BCR-ABL transcripts [abstract]. Blood. 2012, 120 (21 ASH Annual Meeting Abstracts issue): Abstract 916-
Tanaka H, Imagawa J, Okada M, Nakamae H, Hino M, Murai K, Ishida Y, Kumagai T, Sato S, Ohashi K, Sakamaki H, Wakita H, Uoshima N, Nakagawa Y, Minami Y, Ogasawara M, Takeoka T, Akasaka H, Morita S, Sakamoto J, Kimura S: Discontinuation of dasatinib in patients with CML who have maintained complete molecular response for at least one year: results from a prospective discontinuation (DADI) trial [abstract]. Am Soc Hematol. 2013, 122 (21 ASH Annual Meeting Abstracts issue): Abstract 3998-
Breccia M, Alimena G, Baccarani M, Bocchia M, Di Raimondo F, Gambacorti-Passerini C, Gozzini A, Morra E, Pane F, Pregno P, Rege-Cambrin G, Rosti G, Specchia G, Vigneri P, Saglio G: Current management of CML patients: summary of the Italian Consensus Meeting held in Rome, April 11-12, 2013. Crit Rev Oncol Hematol. 2013, 12: 17-
La Nasa G, Caocci G, Littera R, Atzeni S, Vacca A, Mulas O, Langiu M, Greco M, Orrù S, Orrù N, Floris A, Carcassi C: Homozygosity for killer immunoglobulin-like receptor haplotype A predicts complete molecular response to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia patients. Exp Hematol. 2013, 41: 424-431. 10.1016/j.exphem.2013.01.008. CrossRefPubMed
Takahashi N, Kyo T, Maeda Y, Sugihara T, Usuki K, Kawaguchi T, Usui N, Okamoto S, Ohe Y, Ohtake S, Kitamura K, Yamamoto M, Teshima H, Motoji T, Tamaki T, Sawada K, Ohyashiki K: Discontinuation of imatinib in Japanese patients with chronic myeloid leukemia. Haematologica. 2012, 97: 903-906. 10.3324/haematol.2011.056853. CrossRefPubMedPubMedCentral
- Safe discontinuation of nilotinib in a patient with chronic myeloid leukemia: a case report
Giorgio La Nasa
- BioMed Central