TY - JOUR
T1 - Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results
AU - Mauro, Michael J.
AU - Hughes, Timothy P.
AU - Kim, Dong Wook
AU - Rea, Delphine
AU - Cortes, Jorge E.
AU - Hochhaus, Andreas
AU - Sasaki, Koji
AU - Breccia, Massimo
AU - Talpaz, Moshe
AU - Ottmann, Oliver
AU - Minami, Hironobu
AU - Goh, Yeow Tee
AU - DeAngelo, Daniel J.
AU - Heinrich, Michael C.
AU - Gómez-García de Soria, Valle
AU - le Coutre, Philipp
AU - Mahon, Francois Xavier
AU - Janssen, Jeroen J.W.M.
AU - Deininger, Michael
AU - Shanmuganathan, Naranie
AU - Geyer, Mark B.
AU - Cacciatore, Silvia
AU - Polydoros, Fotis
AU - Agrawal, Nithya
AU - Hoch, Matthias
AU - Lang, Fabian
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/5
Y1 - 2023/5
N2 - Asciminib is approved for patients with Philadelphia chromosome–positive chronic-phase chronic myeloid leukemia (CML-CP) who received ≥2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-label, nonrandomized trial (NCT02081378) assessing the safety, tolerability, and antileukemic activity of asciminib monotherapy 10–200 mg once or twice daily in 115 patients with CML-CP without T315I (data cutoff: January 6, 2021). After ≈4-year median exposure, 69.6% of patients remained on asciminib. The most common grade ≥3 adverse events (AEs) included increased pancreatic enzymes (22.6%), thrombocytopenia (13.9%), hypertension (13.0%), and neutropenia (12.2%); all-grade AEs (mostly grade 1/2) included musculoskeletal pain (59.1%), upper respiratory tract infection (41.7%), and fatigue (40.9%). Clinical pancreatitis and arterial occlusive events (AOEs) occurred in 7.0% and 8.7%, respectively. Most AEs occurred during year 1; the subsequent likelihood of new events, including AOEs, was low. By data cutoff, among patients without the indicated response at baseline, 61.3% achieved BCR::ABL1 ≤ 1%, 61.6% achieved ≤0.1% (major molecular response [MMR]), and 33.7% achieved ≤0.01% on the International Scale. MMR was maintained in 48/53 patients who achieved it and 19/20 who were in MMR at screening, supporting the long-term safety and efficacy of asciminib in this population. [Figure not available: see fulltext.].
AB - Asciminib is approved for patients with Philadelphia chromosome–positive chronic-phase chronic myeloid leukemia (CML-CP) who received ≥2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-label, nonrandomized trial (NCT02081378) assessing the safety, tolerability, and antileukemic activity of asciminib monotherapy 10–200 mg once or twice daily in 115 patients with CML-CP without T315I (data cutoff: January 6, 2021). After ≈4-year median exposure, 69.6% of patients remained on asciminib. The most common grade ≥3 adverse events (AEs) included increased pancreatic enzymes (22.6%), thrombocytopenia (13.9%), hypertension (13.0%), and neutropenia (12.2%); all-grade AEs (mostly grade 1/2) included musculoskeletal pain (59.1%), upper respiratory tract infection (41.7%), and fatigue (40.9%). Clinical pancreatitis and arterial occlusive events (AOEs) occurred in 7.0% and 8.7%, respectively. Most AEs occurred during year 1; the subsequent likelihood of new events, including AOEs, was low. By data cutoff, among patients without the indicated response at baseline, 61.3% achieved BCR::ABL1 ≤ 1%, 61.6% achieved ≤0.1% (major molecular response [MMR]), and 33.7% achieved ≤0.01% on the International Scale. MMR was maintained in 48/53 patients who achieved it and 19/20 who were in MMR at screening, supporting the long-term safety and efficacy of asciminib in this population. [Figure not available: see fulltext.].
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U2 - 10.1038/s41375-023-01860-w
DO - 10.1038/s41375-023-01860-w
M3 - Article
C2 - 36949155
AN - SCOPUS:85150733462
SN - 0887-6924
VL - 37
SP - 1048
EP - 1059
JO - Leukemia
JF - Leukemia
IS - 5
ER -