Complications
Pleural effusions may complicate treatment with dasatinib in approximately 20% of patients through an unknown mechanism. An immune-mediated mechanism has been postulated based on reports of high lymphocyte counts.[101]
Patients may present with worsening shortness of breath.
Consideration should be given to dose interruption, concomitant use of diuretics, short-term corticosteroid therapy, or switching to an alternative tyrosine kinase inhibitor.[101][102]
Dasatinib is associated with an increased risk of pulmonary arterial hypertension, in 0.5% to 3% of patients.
Patients may present with worsening shortness of breath in the absence of pleural effusions, or any other cause of dyspnoea.
Consideration should be given to dose interruption, or switching to an alternative tyrosine kinase inhibitor.
The patient should be referred to a cardiologist or other expert in pulmonary hypertension for assessment and management.[103]
Ponatinib is associated with arterial occlusions, venous thromboembolism, heart failure, pancreatitis, and hepatotoxicity.
Treatment should be interrupted if there is cardiovascular toxicity, pancreatitis, or hepatotoxicity; a decision to re-start should be guided by a benefit-risk assessment. Dose reduction may limit risk. Specialty care (cardio-oncology) should be sought where feasible.
Grade 3 or 4 myelosuppression can occur. Patients present with anaemia, neutropenia, or thrombocytopenia.
Treatment is withdrawal of TKI until toxicity improves to grade 2 or better. Consideration of appropriate growth factor support is feasible. Therapy is re-started and the dose is lowered by 30%.[99] National Cancer Institute: Cancer Therapy Evaluation Program - common toxicity criteria: blood/bone marrow Opens in new window Results from a network meta-analysis suggest that, in patients with CML, dasatinib may be associated with greater risk for haematological adverse events than other TKIs.[100]
Calcium and electrolyte supplementation can be given.[99]
Topical or systemic corticosteroids can be used to treat skin rashes, and the TKI dose is reduced.[99]
The TKI is withdrawn until QT prolongation resolves.[99]
Electrolyte imbalances are corrected if present.
Patients on nilotinib should be observed for evidence of arrhythmia and advised to take it without food and to avoid grapefruit products. A new formulation of nilotinib without fasting requirements may be available in some countries.
Nilotinib carries a warning for QT prolongation and sudden death. It should be avoided in the presence of long QT syndrome. ECG monitoring before beginning treatment with nilotinib, and 1 week after starting treatment, is recommended.[5]
Patients should avoid drugs that prolong the QT interval and strong CYP3A4 inhibitors.
Patients with CML are at high risk for viral infections, particularly reactivation of latent viruses such as varicella zoster and hepatitis B. Treatment with tyrosine kinase inhibitors (TKIs) may increase the risk of viral reactivation.[105]
Hepatitis serology is recommended as part of the initial work-up for CML, before starting TKI therapy.[5] Close monitoring for viral infections or reactivations is recommended.[105]
Patients with haematological malignancies are at increased risk for severe COVID-19 infection.[106] Guidelines for treating COVID-19 in patients with haematological malignancies are available.[107] Patients with haematological malignancies have an attenuated response to COVID-19 vaccination.[108]
Patients receiving induction chemotherapy and allogeneic haematopoietic stem cell transplant (HSCT) are at greater risk of infection. Appropriate antimicrobial prophylaxis should be considered.[109] Selection of agents varies based on local protocols and individual patient needs. Monitoring for infections is recommended for all patients who have undergone HSCT.
Post-marketing cases of PRES have been reported.[75]
Presenting signs and symptoms may include seizure, headache, decreased alertness, altered mental functioning, vision loss, and other visual and neurological disturbances.
Treatment should be interrupted if PRES is confirmed; a decision to re-start should be guided by a benefit-risk assessment.
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