TY - JOUR
T1 - Asciminib monotherapy as frontline treatment of chronic phase chronic myeloid leukemia
T2 - results from the ASCEND study
AU - Yeung, David T.
AU - Shanmuganathan, Naranie
AU - Reynolds, John
AU - Branford, Susan
AU - Walia, Mannu
AU - Yong, Agnes S.M.
AU - Shortt, Jake
AU - Chee, Lynette
AU - Viiala, Nicholas
AU - Cunningham, Ilona
AU - Ross, David M.
AU - D'Souza, Alwyn
AU - Wright, Matthew
AU - Harrup, Rosemary
AU - Forsyth, Cecily
AU - Filshie, Robin
AU - Lane, Steven
AU - Browett, Peter
AU - Grove, Carolyn
AU - Grigg, Andrew P.
AU - Hughes, Timothy P.
PY - 2024/11/7
Y1 - 2024/11/7
N2 - 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 Most common reasons for treatment discontinuation were adverse events (6%), loss of response (4%), and withdrawn consent (5%).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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85203254701&partnerID=8YFLogxK
U2 - 10.1182/blood.2024024657
DO - 10.1182/blood.2024024657
M3 - Article
C2 - 39102630
AN - SCOPUS:85203254701
SN - 0006-4971
VL - 144
SP - 1993
EP - 2001
JO - Blood
JF - Blood
IS - 19
ER -