Until recently, the standard of treatment for many hematologic malignancies has largely consisted of combination chemotherapy and radiotherapy. As use of these conventional treatment strategies lessens, the role of targeted therapies continues to expand. However, despite the benefits of novel therapies, unique toxicity profiles warrant vigilant monitoring and personalized management by health care providers.
In a review article published in Expert Review of Hematology, Florian Simon, MD, of the department of internal medicine at the University of Cologne in Germany, and colleagues summarized current literature surrounding the use of novel agents for hematologic malignancies. They also reviewed relevant safety considerations and best practices in the management of therapy-related toxicities.
Novel Therapies and Toxicity Management
The immune checkpoint inhibitors pembrolizumab and nivolumab have been approved by the US Food and Drug Administration (FDA) for the treatment of classical Hodgkin lymphoma in the relapsed/refractory setting. Pembrolizumab was also approved for the treatment of relapsed/refractory primary mediastinal B-cell lymphoma. Overall, checkpoint inhibitor therapy is well tolerated, with a low frequency of immune-related adverse events, but potentially life-threatening toxicities may still occur.
Serious immune-related toxicities include hemophagocytic lymphohistiocytosis, hemolytic anemia, and hemophilia. Gastrointestinal and skin-related adverse effects can also occur within the first 4 to 8 weeks of treatment initiation. Active monitoring of immune-related side-effects is essential, especially in the first 4 months after starting therapy. Typical management of treatment-related toxicities includes discontinuation of therapy or treatment with corticosteroids.
The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib was first approved for the treatment of mantle cell lymphoma and relapsed/refractory chronic lymphocytic leukemia (CLL). Recent evidence has demonstrated improved overall survival in patients with CLL compared with standard chemoimmunotherapy, which has positioned ibrutinib as a first-line therapy in CLL. The toxicity profile of BTK inhibitors is unique, warranting close monitoring of adverse events following initiation of treatment.
Serious ibrutinib-related toxicities include an increased risk of bleeding, particularly for patients receiving concurrent anticoagulation. In long-term follow-up, the majority of reported bleeding events were low grade; however, patients requiring therapeutic anticoagulation should be closely monitored for intracranial hemorrhage and other serious bleeding events. Additional side effects include opportunistic infections and cardiovascular complications such as atrial fibrillation and hypertension.