PMID- 27121688 OWN - NLM STAT- MEDLINE DCOM- 20170828 LR - 20231105 IS - 1476-5551 (Electronic) IS - 0887-6924 (Print) IS - 0887-6924 (Linking) VI - 30 IP - 8 DP - 2016 Aug TI - European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. PG - 1648-71 LID - 10.1038/leu.2016.104 [doi] AB - Most reports on chronic myeloid leukaemia (CML) treatment with tyrosine kinase inhibitors (TKIs) focus on efficacy, particularly on molecular response and outcome. In contrast, adverse events (AEs) are often reported as infrequent, minor, tolerable and manageable, but they are increasingly important as therapy is potentially lifelong and multiple TKIs are available. For this reason, the European LeukemiaNet panel for CML management recommendations presents an exhaustive and critical summary of AEs emerging during CML treatment, to assist their understanding, management and prevention. There are five major conclusions. First, the main purpose of CML treatment is the antileukemic effect. Suboptimal management of AEs must not compromise this first objective. Second, most patients will have AEs, usually early, mostly mild to moderate, and which will resolve spontaneously or are easily controlled by simple means. Third, reduction or interruption of treatment must only be done if optimal management of the AE cannot be accomplished in other ways, and frequent monitoring is needed to detect resolution of the AE as early as possible. Fourth, attention must be given to comorbidities and drug interactions, and to new events unrelated to TKIs that are inevitable during such a prolonged treatment. Fifth, some TKI-related AEs have emerged which were not predicted or detected in earlier studies, maybe because of suboptimal attention to or absence from the preclinical data. Overall, imatinib has demonstrated a good long-term safety profile, though recent findings suggest underestimation of symptom severity by physicians. Second and third generation TKIs have shown higher response rates, but have been associated with unexpected problems, some of which could be irreversible. We hope these recommendations will help to minimise adverse events, and we believe that an optimal management of them will be rewarded by better TKI compliance and thus better CML outcomes, together with better quality of life. FAU - Steegmann, J L AU - Steegmann JL AD - Servicio de Hematologia y Grupo 44 IIS-IP, Hospital Universitario de la Princesa, Madrid, Spain. FAU - Baccarani, M AU - Baccarani M AD - Department of Hematology and Oncology 'L. and A. Seragnoli', St Orsola University Hospital, Bologna, Italy. FAU - Breccia, M AU - Breccia M AD - Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy. FAU - Casado, L F AU - Casado LF AD - Servicio de Hematologia, Hospital Virgen de la Salud, Toledo, Spain. FAU - Garcia-Gutierrez, V AU - Garcia-Gutierrez V AD - Servicio Hematologia y Hemoterapia, Hospital Universitario Ramon y Cajal, Madrid, Spain. FAU - Hochhaus, A AU - Hochhaus A AD - Hematology/Oncology, Universitatsklinikum Jena, Jena, Germany. FAU - Kim, D-W AU - Kim DW AD - Seoul St Mary's Hospital, Leukemia Research Institute, The Catholic University of Korea, Seoul, South Korea. FAU - Kim, T D AU - Kim TD AD - Medizinische Klinik mit Schwerpunkt Onkologie und Hamatologie, Campus Charite Mitte, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Khoury, H J AU - Khoury HJ AD - Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA. FAU - Le Coutre, P AU - Le Coutre P AD - Medizinische Klinik mit Schwerpunkt Onkologie und Hamatologie, Campus Charite Mitte, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Mayer, J AU - Mayer J AD - Department of Internal Medicine, Hematology and Oncology, Masaryk University Hospital Brno, Brno, Czech Republic. FAU - Milojkovic, D AU - Milojkovic D AD - Department of Haematology Imperial College, Hammersmith Hospital, London, UK. FAU - Porkka, K AU - Porkka K AD - Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland. AD - Hematology Research Unit, University of Helsinki, Helsinki, Finland. FAU - Rea, D AU - Rea D AD - Service d'Hematologie Adulte, Hopital Saint-Louis, APHP, Paris, France. FAU - Rosti, G AU - Rosti G AD - Department of Hematology and Oncology 'L. and A. Seragnoli', St Orsola University Hospital, Bologna, Italy. FAU - Saussele, S AU - Saussele S AD - III. Med. Klinik Medizinische Fakultat Mannheim der Universitat Heidelberg, Mannheim, Germany. FAU - Hehlmann, R AU - Hehlmann R AD - Medizinische Fakultat Mannheim der Universitat Heidelberg, Mannheim, Germany. FAU - Clark, R E AU - Clark RE AD - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. LA - eng PT - Journal Article PT - Review DEP - 20160428 PL - England TA - Leukemia JT - Leukemia JID - 8704895 RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM CIN - Leukemia. 2017 Mar;31(3):771-772. PMID: 27909345 CIN - Leukemia. 2017 Mar;31(3):772-773. PMID: 27922619 MH - Drug-Related Side Effects and Adverse Reactions MH - Humans MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*complications/drug therapy MH - Protein Kinase Inhibitors/*adverse effects/therapeutic use MH - Protein-Tyrosine Kinases/antagonists & inhibitors PMC - PMC4991363 COIS- Authors declare the following relationships with pharmaceutical companies: Amgen- receipt of honoraria (GR); Ariad-receipt of honoraria: (JLS, MB, MaB, VG-G, DWK, HJK, PLC, DM, DR, GR and SS) and research funding (JLS, LFC, VG-G, AH, DWK, PLC and GR); Bristol-Myers-Squibb-receipt of honoraria (JLS, MB, MaB, LFC, VG-G, AH, DWK, HJK, PLC, DM, KP, DR, GR, SS, RH and REC), research funding (JLS, LFC, VG-G, DWK, JM, KP, GR, SS and REC) and nonfinancial support (JM); MSD- research support (AH); Novartis-receipt of honoraria (JLS, MB, MaB, LFC, VG-G, DWK, HJK, PLC, DM, KP, DR, GR, SS and REC), research funding (JLS, LFC, VG-G, AH, DWK, JM, KP, GR, SS, RH and REC) and nonfinancial support (JM); ILYANG-receipt of honoraria (DWK) and research funding (DWK); Pfizer-receipt of honoraria (JLS, MB, MaB, LFC, VG-G, DWK, HJK, PLC, DM, KP, DR, GR, SS and REC) and research funding (JLS, LFC, VG-G, AH, DWK, KP, GR and REC); Roche-receipt of honoraria (GR); Sanofi-receipt of honoraria (REC) and research funding (REC); Teva-receipt of honoraria (HJK). EDAT- 2016/04/29 06:00 MHDA- 2017/08/29 06:00 PMCR- 2016/08/19 CRDT- 2016/04/29 06:00 PHST- 2016/02/29 00:00 [received] PHST- 2016/04/18 00:00 [accepted] PHST- 2016/04/29 06:00 [entrez] PHST- 2016/04/29 06:00 [pubmed] PHST- 2017/08/29 06:00 [medline] PHST- 2016/08/19 00:00 [pmc-release] AID - leu2016104 [pii] AID - 10.1038/leu.2016.104 [doi] PST - ppublish SO - Leukemia. 2016 Aug;30(8):1648-71. doi: 10.1038/leu.2016.104. Epub 2016 Apr 28.