Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors

Abstract

(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3-4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs.

Keywords: asciminib; chronic myeloid leukemia; drug intolerance; toxicities.

Figure 1

Discontinuations of asciminib divided by cause at the end of the follow-up period. Pts, patients. * Causes of deaths: pharyngeal neoplasm, hepatic adenocarcinoma, skin ulcer with calciphylaxis, and two unknown causes.

Figure 2

Frequency of adverse effects observed with asciminib. In pale orange: frequency of grade 1–2 adverse effects. In blue color: frequency of grade 3–4 adverse effects. AOE, arterial occlusive event. * Worsening of previous peripheral arterial disease.

Figure 3

Frequency of adverse effects with asciminib in intolerant (pale orange) versus resistant (blue) patients.

Figure 4

(a) Frequency of hematologic toxicity with previous TKI versus asciminib. (b) Frequency of extra-hematologic toxicity with previous TKI versus asciminib. In pale orange to brown: the reported frequency of cytopenias for the different lines prior to asciminib. TKI1 refers to the first line of treatment and TKI2–5 to the successive lines. All previous lines correspond to one of the classical TKIs: either imatinib, dasatinib, nilotinib, bosutinib, or ponatinib. In blue color: the frequency reported with asciminib.

Figure 4

(a) Frequency of hematologic toxicity with previous TKI versus asciminib. (b) Frequency of extra-hematologic toxicity with previous TKI versus asciminib. In pale orange to brown: the reported frequency of cytopenias for the different lines prior to asciminib. TKI1 refers to the first line of treatment and TKI2–5 to the successive lines. All previous lines correspond to one of the classical TKIs: either imatinib, dasatinib, nilotinib, bosutinib, or ponatinib. In blue color: the frequency reported with asciminib.