Asciminib Monotherapy as Frontline Treatment of Chronic-Phase Chronic Myeloid Leukemia: Results from the ASCEND Study.

Autor:	Yeung DT; Royal Adelaide Hospital, Adelaide, Australia., Shanmuganathan N; South Australian Health & Medical Research Institute (SAHMRI), Adelaide, Australia., Reynolds J; Alfred Health and Monash University, Melbourne, VIC, Australia., Branford S; Centre for Cancer Biology, SA Pathology, Adelaide, Australia., Walia M; ALLG, Richmond, Australia., Yong AS; Royal Perth Hospital, Australia., Shortt J; Monash University, Clayton, Australia., Chee L; The Royal Melbourne Hospital/ Peter MacCallum Cancer Centre, Melbourne, Australia., Viiala N; Liverpool Hospital, Sydney, Australia., Cunningham I; Concord Hospital University of Sydney, Sydney, Australia., Ross DM; Flinders Medical CEntre, Australia., D'Souza AB; Wellington Regional Hospital, Wellington, New Zealand., Wright M; Fiona Stanley Hospital, Murdoch, Australia., Harrup RA; Royal Hobart Hospital, HOBART, Australia., Forsyth CJ; Gosford Hospital, North Gosford, Australia., Filshie R; St Vincent's Hospital, melbourne, Australia., Lane SW; Queensland Institute of Medical Research, Brisbane, Australia., Browett PJ; The University of Auckland, Auckland, New Zealand., Grove CS; Sir Charles Gairdner Hospital/PathWest, Nedlands, Australia., Grigg AA; Austin Hospital, Melbourne, Australia., Hughes TP; South Australian Health and Medical Research Institute, Adelaide, Australia.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Aug 05. Date of Electronic Publication: 2024 Aug 05.
DOI:	10.1182/blood.2024024657
Abstrakt:	Asciminib is a myristoyl site BCR::ABL1 inhibitor approved for chronic phase chronic myeloid leukaemia (CP-CML) patients failing ≥2 prior lines of therapy. The Australasian Leukaemia & Lymphoma Group (ALLG) conducted the ASCEND study to assess efficacy of asciminib for newly-diagnosed CP-CML. Patients commenced asciminib 40 mg twice daily (BID) and thereafter were managed according to molecular milestones. Patients with treatment failure, defined as BCR::ABL1 >10% (IS) 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 1-10% at 6 months, >0.1-1% at 12 months, or >0.01%-1% at 18 months, the asciminib dose was increased to 80 mg BID. With a median follow-up of 21 months (range 0-36), 82/101 patients continue asciminib. The most frequent reasons for treatment discontinuation were adverse events (6%), loss of response (4%) and withdrawn consent (5%). There were no deaths; one patient developed lymphoid blast crisis at 6 months. The co-primary endpoints were early molecular response (BCR::ABL1 ≤10% at 3 months), achieved in 93% (96% CI 86-97%), and major molecular response by 12 months achieved in 79%; (95% CI 69.7-86.8%), respectively. The cumulative incidence of MR4.5 was 53% by 24 months. One patient had 2 cerebrovascular events; no other arterial occlusive events were reported. Asciminib as frontline therapy in CP-CML produces high rates of molecular response with excellent tolerance and a low rate of discontinuation for toxicity. (ANZ Clinical Trials Registry ACTRN12620000851965). (Copyright © 2024 American Society of Hematology.)
Databáze:	MEDLINE
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