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Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study

TP. Hughes, G. Saglio, J. Geissler, DW. Kim, E. Lomaia, J. Mayer, A. Turkina, S. Kapoor, AP. Cardoso, B. Nieman, S. Quenet, JE. Cortes

. 2024 ; 17 (1) : 125. [pub] 20241218

Language English Country England, Great Britain

Document type Journal Article, Randomized Controlled Trial, Clinical Trial, Phase II, Multicenter Study

Persistent link   https://www.medvik.cz/link/bmc25003008

BACKGROUND: Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy. The phase II ASC4MORE trial investigated the strategy of adding asciminib to imatinib in patients who have not achieved deep molecular response with imatinib. METHODS: In ASC4MORE, 84 patients with CML in chronic phase not achieving deep molecular response after ≥ 1 year of imatinib therapy were randomized to asciminib 40 or 60 mg once daily (QD) add-on to imatinib 400 mg QD, continued imatinib 400 mg QD, or switch to nilotinib 300 mg twice daily. RESULTS: More patients in the asciminib 40- and 60-mg QD add-on arms (19.0% and 28.6%, respectively) achieved MR4.5 (BCR::ABL1 ≤ 0.0032% on the International Scale) at week 48 (primary endpoint) than patients in the continued imatinib (0.0%) and switch to nilotinib (4.8%) arms. Fewer patients discontinued asciminib 40- and 60-mg QD add-on treatment (14.3% and 23.8%, respectively) than imatinib (76.2%, including crossover patients) and nilotinib (47.6%). Asciminib add-on was tolerable, with rates of AEs and AEs leading to discontinuation less than those with nilotinib, although higher than those with continued imatinib (as expected in these patients who had already been tolerating imatinib for ≥ 1 year). No new or worsening safety signals were observed with asciminib add-on vs the known asciminib monotherapy safety profile. CONCLUSIONS: Overall, these results support asciminib add-on as a treatment strategy to help patients with CML in chronic phase stay on therapy to safely achieve rapid and deep response, although further investigation is needed before this strategy is incorporated into clinical practice. TRIAL REGISTRATION: NCT03578367.

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$a Hughes, Timothy P $u South Australian Health and Medical Research Institute and University of Adelaide, Adelaide, SA, Australia. Tim.Hughes@sahmri.com
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$a BACKGROUND: Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy. The phase II ASC4MORE trial investigated the strategy of adding asciminib to imatinib in patients who have not achieved deep molecular response with imatinib. METHODS: In ASC4MORE, 84 patients with CML in chronic phase not achieving deep molecular response after ≥ 1 year of imatinib therapy were randomized to asciminib 40 or 60 mg once daily (QD) add-on to imatinib 400 mg QD, continued imatinib 400 mg QD, or switch to nilotinib 300 mg twice daily. RESULTS: More patients in the asciminib 40- and 60-mg QD add-on arms (19.0% and 28.6%, respectively) achieved MR4.5 (BCR::ABL1 ≤ 0.0032% on the International Scale) at week 48 (primary endpoint) than patients in the continued imatinib (0.0%) and switch to nilotinib (4.8%) arms. Fewer patients discontinued asciminib 40- and 60-mg QD add-on treatment (14.3% and 23.8%, respectively) than imatinib (76.2%, including crossover patients) and nilotinib (47.6%). Asciminib add-on was tolerable, with rates of AEs and AEs leading to discontinuation less than those with nilotinib, although higher than those with continued imatinib (as expected in these patients who had already been tolerating imatinib for ≥ 1 year). No new or worsening safety signals were observed with asciminib add-on vs the known asciminib monotherapy safety profile. CONCLUSIONS: Overall, these results support asciminib add-on as a treatment strategy to help patients with CML in chronic phase stay on therapy to safely achieve rapid and deep response, although further investigation is needed before this strategy is incorporated into clinical practice. TRIAL REGISTRATION: NCT03578367.
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$a Saglio, Giuseppe $u Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
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$a Geissler, Jan $u CML Advocates Network, Bern, Switzerland
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$a Kim, Dong-Wook $u Uijeongbu Eulji Medical Center, Geumo-Dong, Uijeongbu-si, South Korea
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$a Lomaia, Elza $u Almazov National Medical Research Centre, St Petersburg, Russia
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$a Mayer, Jiri $u Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, and University Hospital Brno, Brno, Czech Republic
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$a Turkina, Anna $u National Medical Research Center for Hematology, Moscow, Russia
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$a Kapoor, Shruti $u Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
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$a Cardoso, Ana Paula $u Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
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$a Nieman, Becki $u Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
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$a Quenet, Sara $u Novartis Pharmaceuticals Corporation, Basel, Switzerland
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$a Cortes, Jorge E $u Georgia Cancer Center, Augusta, GA, USA
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