Twenty-two years after the first patients with chronic myeloid leukemia (CML) were treated with the tyrosine kinase inhibitor (TKI) imatinib, outcome exceeds all expectations: the vast majority of CML patients have achieved normal life expectancy and some patients in sustained deep molecular remissions (DMR) may even be operationally cured in durable treatment-free remissions (TFR). However, some expectations remain unmet. Most patients are not yet cured and require life-long maintenance therapy. Also, progression to blast crisis still occurs in 5–7% of patients and remains a challenge. CML has not become the expected model disease for treating other leukemias or cancers, but the principle of elucidating the pathogenesis as a successful approach for cancer treatment has been impressively demonstrated in CML.

New insights have emerged from maturing long-term academic and commercial clinical trials regarding optimum management of CML. Velocity of response has unexpectedly proved less important than hitherto thought, does not predict survival, and is of unclear relevance for TFR. Serious and cumulative toxicity has been observed with TKI that had been expected to replace imatinib. Generic imatinib has become cost-effective first-line treatment in chronic phase despite chronic low-grade side-effects in many patients. Earlier recognition of CML end-phase by genetic assessment might improve prospects for blast crisis. Treatment discontinuation and TFR has become an important new treatment goal of CML. Duration of DMR (MR4, MR4.5) may be the best predictor of success. To reflect this new situation, the European LeukemiaNet has recently revised and updated its recommendations for treating CML. The presentation will focus on recent developments and on current evidence for treating CML in 2020.