Background: Asciminb is an allosteric BCR-ABL1 inhibitor that has been available for patients with chronic myeloid leukaemia (CML) in the United Kingdom under a managed access program (MAP) from Novartis since 2016. Aims: The aim of this project was to share real-world experience of asciminib use in the UK. Methods: Using a national survey proforma (REC reference: 21/HRA/2157), we collated baseline, outcome and toxicity data on 44 patients treated with asciminib in the UK. Responses were assess using BCR-ABL1 IS values and categorised by ELN criteria. Intolerances were reported using CTCAEv5.0 criteria. Results: The median age at treatment was 58 [22-88] years. Vascular comorbidities were seen in 22 (50%) patients, the most frequent being hypertension (n=12, 27%), peripheral vascular disease (n=6, 14%), AF (n=6, 14%) and ischaemic heart disease (n=6, 14%). Chronic kidney disease was present in 7 (16%) patients. All but one patient was in chronic phase at the time of treatment, but tyrosine kinase domain mutations (TKDM) were common prior to treatment initiation (T315I in 11/44 (25%), other TKDM in 8/44 (18%)). The median number of prior TKIs were 4 [2-5], with 44% of prior lines stopped for resistance, and 56% for intolerance. The most recent TKI was discontinued for resistance in 14 (32%) and intolerance in 30 (68%). Eight (18%) patients had developed pleural effusions on a previous TKIs. Most patients had previously received ponatinib (n=30, 68%) which has been discontinued for resistance in 8 (27%) and intolerance in 22 (73%), with 7 (16%) vascular events on treatment. Five (11%) patients had received prior allogeneic stem cell transplant. At the time of data cut-off, 25 (57%) patients remained on treatment with a median treatment duration of 20 [3-51] months. Reason for treatment discontinuation was resistance (n=7, 16%), intolerance (n= 7, 16%), pregnancy (n=1, 2%), treatment-free remission (n=1, 2%) and non-compliance (n=1, 2%). Two patients died whilst on treatment of unrelated causes. The median daily dose delivered was 240mg [20-400] in patients with T315I-TKDM and 80mg [20-80] in others. While 11 patients had no significant response (including those with early treatment discontinuation for intolerance), 23 (53%) patients achieved MR3 or better, with 14 (32%) achieving MR4 or better. Of 9 patients in MR3 or better at asciminib initiation, 3 (33%) did not tolerate treatment, 2 (22%) maintained their response, and 4 (44%) deepened their response by one category or more. The presence of a non-T315I TKDM was associated with a lower incidence of achieving MR3, with 1 of 6 (16%) evaluable patients in this group achieving MR3 or better, compared with 22 of 31 (71%) evaluable patients with no TKDM or a T315I-only TKDM (p=0.04) (Table1). Haematological toxicity was seen in 17 (38%) patients, and was grade 3-4 in 6 (14%) (predominantly anaemia and thrombocytopaenia). Non-haematological toxicity was reported in 19 (43%) patients (most commonly fatigue (n=4), insomnia (n=3), bone pain (n=2), back pain (n=2), nausea (n=2), fluid retention (n=2)), with only 2 (4%) patients experiencing grade 3-4 toxicity (fatigue in both cases). No worsening of baseline vascular co-morbidity or renal dysfunction was noted. One patient developed a new pleural effusion on the 200mg bd dose, which did not recur on dose reduction. Image:Summary/Conclusion: These data show that asciminib is a well-tolerated, effective treatment for patients who are resistant to or intolerant of multiple TKIs, many of whom often have a number of co-morbidities including vascular disease.