European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia.
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.
Servicio de Hematologia y Grupo 44 IIS-IP, Hospital Universitario de la Princesa, Madrid, Spain.
J L
JL
Steegmann
Department of Hematology and Oncology 'L. and A. Seràgnoli', St Orsola University Hospital, Bologna, Italy.
M
M
Baccarani
Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
M
M
Breccia
Servicio de Hematologia, Hospital Virgen de la Salud, Toledo, Spain.
L F
LF
Casado
Servicio Hematología y Hemoterapia, Hospital Universitario Ramón y Cajal, Madrid, Spain.
V
V
García-Gutiérrez
Hematology/Oncology, Universitätsklinikum Jena, Jena, Germany.
A
A
Hochhaus
Seoul St Mary's Hospital, Leukemia Research Institute, The Catholic University of Korea, Seoul, South Korea.
D-W
DW
Kim
Medizinische Klinik mit Schwerpunkt Onkologie und Hämatologie, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
T D
TD
Kim
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
H J
HJ
Khoury
Medizinische Klinik mit Schwerpunkt Onkologie und Hämatologie, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
P
P
Le Coutre
Department of Internal Medicine, Hematology and Oncology, Masaryk University Hospital Brno, Brno, Czech Republic.
J
J
Mayer
Department of Haematology Imperial College, Hammersmith Hospital, London, UK.
D
D
Milojkovic
Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.|Hematology Research Unit, University of Helsinki, Helsinki, Finland.
K
K
Porkka
Service d'Hématologie Adulte, Hôpital Saint-Louis, APHP, Paris, France.
D
D
Rea
Department of Hematology and Oncology 'L. and A. Seràgnoli', St Orsola University Hospital, Bologna, Italy.
G
G
Rosti
III. Med. Klinik Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
S
S
Saussele
Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
R
R
Hehlmann
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
R E
RE
Clark
D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications* / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases