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Forty-nine patients treated with asciminib under a managed access program in the UK were evaluated for toxicity and response. Intolerance, rather than resistance (65% vs. 35%), was the most common reason for cessation of the last-line of treatment but asciminib was well tolerated, with most patients (29, 59%) remaining on treatment at a median of 14 months follow-up, and only 6 (12%) stopping for intolerance. Of 44 patients assessable for response, 29 (66%) achieved a complete cytogenetic response (CCyR) or better, with poorer responses seen in those stopping their last-line of therapy for resistance. Fewer patients with a prior history of a non-T315I-<jats:italic>BCR::ABL1<\/jats:italic> single nucleotide variant (BSNV), or a non-T315I-BSNV detectable at baseline achieved CCyR. Serial tracking of BSNV by next generation sequencing demonstrated clonal expansion of BSNV-harbouring populations, which in some settings was associated with resistance (E459K, F317L, F359I), while in others was seen in the context of ongoing response, often with intensified dosing (T315I, I502F). 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JB: Speaker fees and advisory board (Novartis and Incyte). MC: Research funding (Cyclacel and Incyte), advisory board member (Novartis, Incyte, Jazz Pharmaceuticals, Pfizer and Servier), honoraria (Astellas, Novartis). RF: Honoraria (Novartis, BMS), advisory board (CTI biopharma and GSK). GHa: Honoraria and Speakers fees (Novartis, Pfizer, Incyte), Advisory board (Novartis), DA: Speaker fees (Incyte). JFA: Honoraria, research funding, and speakers bureau (Incyte, Pfizer); honoraria and speakers bureau (Bristol Myers Squibb, Novartis). DM: Honoraria (Incyte, Novartis, Pfizer, Ascentage Pharma), Research funding (Incyte and Pfizer). The remaining authors (CH VO, SC FF AK, DR, PG, SF, GHo, MR, CA, AC, TC, NC, AD, PF, PG, SH, BJPH, JH, SM, KR, JK) report no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This work in this study was performed in line with current guidance (with UKAS accredited assays), and the study was approved by a local research ethics committee (HRA and Health and Care Research Wales, reference 21\/HRA\/2157).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}