New drugs in CLL may also carry specific risks of adverse effects. How to minimize and manage them?

The introduction of new treatment options, including targeted therapies, allows for individualized CLL therapy. However, their use requires the optimization of current approaches to prophylaxis and supportive care treatment due to their specific adverse effect profiles. Knowledge of individual risk for higher incidence of adverse effects can ultimately and should significantly reduce the morbidity associated with modern CLL treatment.

Some specific adverse effects of new drugs are mentioned in a recent review by hematologists from the University of Lodz:

• Most drugs used in CLL therapy can cause cytopenia, especially neutropenia. In the case of severe neutropenia, it is advisable to temporarily administer growth factors to support granulopoiesis.
• Patients with CLL, especially those currently undergoing treatment, are at a significant risk of infections, including opportunistic ones. Active monitoring for infections and prophylaxis can reduce the risk of serious infectious complications.
• Some new drugs, particularly venetoclax, may be associated with an increased risk of tumor lysis syndrome (TLS). When administering, it is necessary to escalate the dose gradually and proactively monitor for the possible development of TLS, taking preventive steps if necessary.
• Some drugs can lead to hepatic damage through various mechanisms. Idelalisib is associated with a higher risk of hepatotoxicity, likely promoted by the inhibition of delta kinase PI3K subunits in regulatory T lymphocytes.
• Therapy with Bruton's tyrosine kinase (BTK) inhibitors, especially ibrutinib, can be associated with an increased tendency to bleed. Concurrent administration of anticoagulants and ibrutinib is not recommended.
• Diarrhea is often reported in patients treated with ibrutinib and idelalisib, which can lead to dose reduction or interruption of treatment. If diarrhea does not resolve within 48 hours and an infectious cause is excluded, steroids may be administered.
• Patients receiving idelalisib are at risk of developing non-infectious pneumonitis and should be treated with high doses of corticosteroids if this complication occurs.
• In patients treated with ibrutinib, a higher incidence of atrial fibrillation (AF) has been observed. However, it must be noted that a prior diagnosis of AF or other arrhythmias should not be a contraindication for therapy with this drug.

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Source: Iskierska-Jadzewska E., Robat T. Minimizing and managing treatment-associated complications in patients with chronic lymphocytic leukemia. Expert Rev Hematol 2020 Jan; 13 (1): 39–53, doi: 10.1080/17474086.2020.1696185.