Description

Chronic myeloid leukemia (CML) is a myeloproliferative disorder. Based on the increase in the number of patients, the drug tyrosine kinase inhibitors (TKIs) for the treatment of CML is also being continuously studied. The first-generation inhibitor is imatinib. Dasatinib is the second generation of TKIs which conclude ilotinib and bosutinib. The third-generation TKI is ponatinib. Dasatinib is approved for patients with chronic and advanced phase CML[1]. Studies have found that dasatinib induced significantly higher rates of cytogenetic and molecular responses than imatinib.

Applications

Dasatinib is indicated for the treatment of chronic myeloid leukemia (CML), where it targets the fusion protein BCRABL, derived from the Philadelphia translocation (Ph+). Dasatinib inhibits several tyrosine kinases, including BCRABL, the Src family (LYN, HCK), c-kit, ephrin receptor (EPH), and platelet-derived growth factor receptor β (PDGFβ). The ability to inhibit several tyrosine kinases has made it an attractive therapeutic option beyond CML and Ph+ acute lymphoblastic leukemia. These include other hematologic malignancies such as chronic eosinophilic leukemia and systemic mastocytosis; solid tumors such as breast, prostate, and melanoma; and conditions such as primary myelofibrosis and systemic sclerosis-associated interstitial lung disease[2-3].

Side effects

Dasatinib has a wide range of applications in the medical field, but its side effects cannot be ignored. Skin rashes are common, occurring in about a quarter of patients treated, and are generally mild. Most skin rashes were graded as mild, with only 1.1% being high grade. Most were symptomatic with pruritus dominating. Other symptoms reported included tenderness, burning pain, and skin tightening. Skin reactions listed with this drug include: erythema, erythema multiforme, urticaria, photosensitivity, nail disorders, neutrophilic dermatosis, palmoplantar erythrodysesthesia syndrome, asteatosis, leukocytoclastic vasculitis, skin ulcer, skin fibrosis, and Stevens-Johnson syndrome[4]. In addition to skin problems, patients may get an infection or bleed more easily. Some people using dasatinib have developed a rare but serious condition called pulmonary arterial hypertension (PAH). PAH occurs when blood pressure increases inside the arteries in your lungs. This makes it harder for your heart to pump blood through the lungs, which also weakens muscles in the heart. PAH may be irreversible if not promptly treated, and this condition can be fatal.

References

[1] Mestermann ;K, et al. The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells. Science Translational Medicine, 2019; 11.

[2] Rousselot P, et al. Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients. British Journal of Haematology, 2021; 194: 393-402.

[3] Shen S, et al. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncology, 2020; 6: 358-366.

[4] Bergman J, et al. Recurrent and Fixed Neutrophilic Dermatosis Associated With Dasatinib. Journal of Cutaneous Medicine and Surgery, 2018; 22.