Asciminib targets the BCR::ABL1 myristoyl pocket, maintaining activity against BCR::ABL1 T315I, which is resistant to most approved adenosine triphosphate-competitive tyrosine kinase inhibitors. We report updated phase I results (NCT02081378) assessing safety/tolerability and antileukemic activity of asciminib monotherapy 200 mg twice daily in 48 heavily pretreated patients with T315I-mutated chronic-phase chronic myeloid leukemia (CML-CP; data cutoff: January 6, 2021). With 2 years' median exposure, 56.3\% of patients continued receiving asciminib. Overall, 62.2\% of evaluable patients achieved BCR::ABL1 <= 1\% on the International Scale (IS); 47.6\% and 81.3\% of ponatinib-pretreated and -naive patients, respectively, achieved BCR::ABL1 IS <= 1\%. Of 45 evaluable patients, 48.9\% achieved a major molecular response (MMR, BCR::ABL1 IS <= 0.1\%), including 34.6\% and 68.4\% of ponatinib-pretreated and -naive patients, respectively. MMR was maintained until data cutoff in 19 of 22 patients who achieved it. The most common grade >= 3 adverse events (AEs) included increased lipase level (18.8\%) and thrombocytopenia (14.6\%). Five (10.4\%) patients experienced AEs leading to discontinuation, including 2 who discontinued asciminib and died due to COVID-19; these were the only deaths reported. These results show asciminib's effectiveness, including in almost 50\% of ponatinib pretreated patients, and confirm its risk-benefit profile, supporting its use as a treatment option for T315I-mutated CML-CP.
Asciminib monotherapy in patients with chronic-phase chronic myeloid leukemia with the T315I mutation after ≥1 prior tyrosine kinase inhibitor: 2-year follow-up results / Cortes, Jorge E.; Sasaki, Koji; Kim, Dong-Wook; Hughes, Timothy P.; Etienne, Gabriel; Mauro, Michael J.; Hochhaus, Andreas; Lang, Fabian; Heinrich, Michael C.; Breccia, Massimo; Deininger, Michael; Goh, Yeow Tee; Janssen, Jeroen J. W. M.; Talpaz, Moshe; de Soria, Valle Gomez Garcia; le Coutre, Philipp; Deangelo, Daniel J.; Damon, Andrea; Cacciatore, Silvia; Polydoros, Fotis; Agrawal, Nithya; Rea, Delphine. - In: LEUKEMIA. - ISSN 0887-6924. - 38:7(2024), pp. 1455-1468. [10.1038/s41375-024-02278-8]
Asciminib monotherapy in patients with chronic-phase chronic myeloid leukemia with the T315I mutation after ≥1 prior tyrosine kinase inhibitor: 2-year follow-up results
Breccia, Massimo;
2024
Abstract
Asciminib targets the BCR::ABL1 myristoyl pocket, maintaining activity against BCR::ABL1 T315I, which is resistant to most approved adenosine triphosphate-competitive tyrosine kinase inhibitors. We report updated phase I results (NCT02081378) assessing safety/tolerability and antileukemic activity of asciminib monotherapy 200 mg twice daily in 48 heavily pretreated patients with T315I-mutated chronic-phase chronic myeloid leukemia (CML-CP; data cutoff: January 6, 2021). With 2 years' median exposure, 56.3\% of patients continued receiving asciminib. Overall, 62.2\% of evaluable patients achieved BCR::ABL1 <= 1\% on the International Scale (IS); 47.6\% and 81.3\% of ponatinib-pretreated and -naive patients, respectively, achieved BCR::ABL1 IS <= 1\%. Of 45 evaluable patients, 48.9\% achieved a major molecular response (MMR, BCR::ABL1 IS <= 0.1\%), including 34.6\% and 68.4\% of ponatinib-pretreated and -naive patients, respectively. MMR was maintained until data cutoff in 19 of 22 patients who achieved it. The most common grade >= 3 adverse events (AEs) included increased lipase level (18.8\%) and thrombocytopenia (14.6\%). Five (10.4\%) patients experienced AEs leading to discontinuation, including 2 who discontinued asciminib and died due to COVID-19; these were the only deaths reported. These results show asciminib's effectiveness, including in almost 50\% of ponatinib pretreated patients, and confirm its risk-benefit profile, supporting its use as a treatment option for T315I-mutated CML-CP.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
