Asciminib monotherapy as frontline treatment of chronic-phase chronic myeloid leukemia: results from the ASCEND study

• Published in: Blood Vol. 144; no. 19; pp. 1993 - 2001
• Main Authors: Yeung, David T., Shanmuganathan, Naranie, Reynolds, John, Branford, Susan, Walia, Mannu, Yong, Agnes S. M., Shortt, Jake, Chee, Lynette, Viiala, Nicholas, Cunningham, Ilona, Ross, David M., D’Souza, Alwyn, Wright, Matthew, Harrup, Rosemary, Forsyth, Cecily, Filshie, Robin, Lane, Steven, Browett, Peter, Grove, Carolyn, Grigg, Andrew P., Hughes, Timothy P., Grigg, Andrew, Viiala, Nichola
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.11.2024
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2024024657

•Asciminib monotherapy leads to high rates of early and major molecular response in newly diagnosed chronic-phase CML.•Safety and tolerance of asciminib were excellent. [Display omitted] Asciminib is a myristoyl site BCR::ABL1 inhibitor approved for patients with chronic-phase chronic myeloid leukemia (CP-CML) failing ≥2 prior lines of therapy. The Australasian Leukaemia and Lymphoma Group conducted the Asciminib Evaluation in Newly Diagnosed CML study to assess efficacy of asciminib for newly diagnosed CP-CML. Patients commenced asciminib 40 mg twice daily. Patients with treatment failure, defined as BCR::ABL1 of >10% at 3 or 6 months, or >1% at 12 or 18 months, received either imatinib, nilotinib, or dasatinib in addition to asciminib. In patients with suboptimal response, defined as levels of 1% to 10% at 6 months, >0.1% to 1% at 12 months, or >0.01% to 1% at 18 months, the asciminib dose was increased to 80 mg twice daily. With a median follow-up of 21 months (range, 0-36), 82 of 101 patients continue asciminib. Most common reasons for treatment discontinuation were adverse events (6%), loss of response (4%), and withdrawn consent (5%). There were no deaths; 1 patient developed lymphoid blast crisis. The coprimary end points were early molecular response (BCR::ABL1 of ≤10% at 3 months), achieved in 93% (96% confidence interval [CI], 86-97%), and major molecular response by 12 months achieved in 79%; (95% CI, 70-87%), respectively. Cumulative incidence of molecular response 4.5 was 53% by 24 months. One patient had 2 cerebrovascular events; no other arterial occlusive events were reported. Asciminib as frontline CP-CML therapy leads to high rates of molecular response with excellent tolerance and a low rate of discontinuation for toxicity. This trial was registered at https://www.anzctr.org.au/ as #ACTRN12620000851965. Yeung and colleagues report results of the ASCEND study from the Australasian Leukaemia and Lymphoma Group, which assessed the efficacy of asciminib, a novel allosteric BCR::ABL1 inhibitor, as first-line therapy for chronic-phase chronic myeloid leukemia (CP-CML). Early (at 3 months) and major (at 12 months) molecular responses were seen in 93% and 79% of patients, respectively, and therapy was well tolerated. This study supports the efficacy of asciminib for frontline therapy of CP-CML.