P686: real-world efficacy profile of asciminib in an italian, multi-resistant chronic-phase chronic myeloid leukemia (cp-cml) patient population

Background: Asciminib (Asc) is the first tyrosine kinase inhibitor (TKI) to Specifically Target the ABL Myristoyl Pocket (STAMP). The recent update of the ASCEMBL study demonstrated a superior efficacy with a good tolerability of Asc compared to bosutinib in chronic phase chronic myeloid leukemia (CP-CML) patients intolerant or refractory to ≥2 TKIs (major molecular response (MMR) rate at week 96: 37.6% vs 15.8%; treatment discontinuation 7.7% vs 26.3%) (Rea et al, 2022) Aims: Here we present the real-world clinical outcomes of 77 Italian TKI-resistant/intolerant CP-CML patients in 3rd line or later lines who received Asc through a Managed Access Program (MAP) approved by Novartis, between April 2019 and October 2022 in 41 Italian institutions. Methods: BCR::ABL1/ABL ratio was expressed as % IS in all centers. Efficacy was analyzed by comparing the response registered at approximately 3 months vs the response at baseline as well as comparing the best response registered at the last data cut off. Patient recruitment and dosing regimen were recorded according to the MAP recommendations. Results: Median time of Asc treatment was 8.5 (3-38) months for the whole cohort. The median number of prior TKIs were 3 (2-5) and 51.7% of patients were reported to have ≥3 comorbidities. Switch to Asc occurred for resistance in 44 patients (57.1%) and for intolerance in 33 patients (42.9%). Eleven patients (14.3%) harbored a T315I mutation. Forty-three patients (55.8%) had a prior exposure to ponatinib and 38 of them (88.4%) had ponatinib as last TKI before switching to Asc. All the T315I patients had a ponatinib exposure before the switch, with a mean daily dose of 303.94 mg (68.9-400). At the time of data cut-off, 60 patients (77.9%) remained on treatment with a median treatment duration of 8.5 months. Reason for Asc discontinuation was progression (n=5, 6.4%), resistance (n=2, 2.5%), intolerance (n=2, 2.5%), death (n=1, 1.2%) and allogenic transplant (n=7, 9%). Sixty-eight out of 77 (88.3%) and 70/77 (90.9%) patients maintained or improved their previous response at 3 months and at the best response time point respectively (Fig 1A). After 3 months, 34/77 (44.2%) patients showed an improvement of previous baseline response with approximately 33% of patients, without MMR response at baseline, that was able to reach at least this response. At the same time point, considering patients who enter the MAP without MR2, 51% achieved this response level. Interestingly, we kept observing that previous ponatinib treatment determined a reduced probability of reaching MMR when compared to ponatinib naive condition. Specifically, of the 34/43 (79.1%) ponatinib pre-treated patients without an MMR at baseline, 12 (35.3%) reached an MMR in a median time of 3 months whereas 30 out of 34 of ponatinib naive patients without MMR at baseline, 19 of them (63.3%) reached an MMR with a median time of approximately 4 months (Fig 1B). Summary/Conclusion: In this heavily pre-treated population of CML patients most of whom with a high comorbidity burden, asciminib demonstrated fast and sustained responses. Collectively, these results continue to confirm that asciminib has a promising role as standard of care in patients with CP-CML treated with ≥2 prior TKI.Keywords: Chronic myeloid leukemia