Comorbidities and mutations including single‐ and multihit <i>TET2</i> mutations in relation to outcome in chronic myelomonocytic leukaemia—A population‐based study

To explore the relation between disease characteristics, comorbidities, mutations and overall survival (OS) in chronic myelomonocytic leukaemia (CMML), we collected data from a population-based cohort of 149 consecutive patients. TET2 mutation (TET2^MT) was associated with higher haemoglobin, less leucocytosis and longer OS compared to no TET2^MT (TET2^WT), despite patients being significantly older. Patients with multihit TET2^MT had the most favourable outcome (HR 0.55, CI 0.35-0.88, p < 0.05). Multihit TET2^MT was associated with lower lactate dehydrogenase and less monocytosis, indicating multihit TET2^MT as a separate disease entity. Autoimmune disease (AID) was present in 33.6% of patients, with no association to any mutations. In multivariable analysis, the number of TET2^MT was demonstrated to be an independent factor associated with improved OS, and RUNX1^MT, myeloproliferative CMML (CMML-MP), ECOG >0 and transfusion dependence remained significant adverse factors. Internal validation including cross-validation and correction for optimism consistently demonstrated that a prognostic model containing the number of TET2^MT, RUNX1, CMML-MP, ECOG >0 and transfusion dependence showed better calibration, discrimination and overall performance than CPSS-Mol in predicting OS. Importantly, the addition of TET2 mutation status to CPSS-Mol also improved the CPSS-Mol score performance. Taken together, TET2^MT status, especially multihit TET2^MT, defines a specific CMML phenotype and should be considered in future prognostic scores.