Second-generation tyrosine kinase inhibitors (2GTKI) are more effective in inducing rapid molecular responses than imatinib when used first-line in patients with chronic myeloid leukemia in chronic phase (CML-CP). However, failure of first line-2GTKI (1L-2GTKI) still occurs and there is no consensus regarding subsequent management. We retrospectively analyzed the outcome of 106 CML-CP patients treated with 1L-2GTKI and with a median follow-up of 91 months. 45 patients (42.4%) switched to an alternative TKI, 28 for intolerance (26.4%) and 17 (16%) for resistance. Most patients who remained on 1L-2GTKI achieved deep molecular responses (DMR) and 15 (14.1%) are in treatment-free remission (TFR). Intolerant patients also obtained DMR, although most required multiple TKI changes and were slower to respond, particularly if treated with 2L-imatinib. Inferior outcomes were observed in resistant patients, who failed alternative 2L-2GTKI and required 3/4GTKI and/or allogeneic hematopoietic stem cell transplant (alloSCT). 7yr-OS was significantly lower for these individuals (66.1%) than for intolerant patients and those who remained on 1L-2GTKI (100% and 97.9%, respectively; p = 0.001). It is apparent that failure of 1L-2GTKI is a challenging problem in modern CML therapy. Intolerance can be effectively managed by switching to an alternative 2GTKI, but resistance requires early consideration of 3/4GTKI.

The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.

The majority of patients with newly diagnosed chronic myeloid leukaemia will enjoy a life expectancy equivalent to that of unaffected individuals, but will remain on life-long treatment with a concomitant requirement for on-going hospital interactions for molecular monitoring and drug dispensing. In order to determine more accurately the frequency of monitoring required, we performed a real-life retrospective single-centre cohort study of 450 patients with chronic myeloid leukaemia in at least major molecular remission (MR3) to analyse the risk of loss of MR3 (defined as at least 2 consecutive RT-qPCR results >0.1% IS). Patient who achieved sustained MR4 (sMR4, BCR-ABL1 RT-qPCR <0.01% IS for 12 months) had a probability of loss of MR3 at 1 and 5 years of 0 and 2.6% (95% CI,1.2-5.4) respectively, compared to 4.4% (95% CI, 1.9-9.8) and 25.4% (95% CI, 16.7-36.7) respectively, in those who achieved sustained MR3 (sMR3) but not sMR4 (p <0.001). No patient who improved their response to a deep molecular level (at least MR4) lost MR3 if they were considered compliant, had no history of resistance and remained on standard dose TKI. MR4 maintained for at least 1 year represents a secure response threshold for patients with chronic myeloid leukaemia, after which no MR3 loss occurs if certain conditions are satisfied (standard TKI dose, full compliance and lack of previous TKI resistance). This finding may justify reduction of the frequency of hospital interaction, with an associated positive impact on quality of life, survivorship and economic burden to both patients and healthcare providers.

The immune impairment related to some haematological malignancies and their treatments is considered responsible for the more severe COVID-19 [1] and the lower response rate to anti-SARS-CoV-2 vacc...