Targeted Therapy For CLL

By Isabella Martire, MD, Board Certified In Oncology

CLL (Chronic Lymphocytic Leukemia) is a disease of the elderly most frequently diagnosed in people over the age of 70. The disease is treated when symptoms develop.

With better understanding of what drives tumor growth in recent years, new targeted agents were developed for the treatment of CLL.

Ibrutinib (Imbrivca) is the first drug developed to target a protein called Bruton's Tyrosine Kinase, which drives cancer cell growths. Ibrutinib is an oral tyrosine kinase inhibitor, which has a response rate of 71% in relapsed CLL irrespective of genomic type. The most common side effects are diarrhea, fatigue, nausea, edema, and upper respiratory infection. It is not indicated in patients who are on long-term anticoagulation with warfarin because of the risk of CNS bleeding, it is effective as a single agent.

Idelalisib (Zydelig) is a tyrosine kinase inhibitor of the delta isoform of phosphatidylinositol 3-kinase used in combination with rituximab. The two-drug combination resulted in a response rate of 81% in relapsed CLL. The most common side effects from idelalisib are diarrhea, fever, fatigue, abdominal pain, chills, rash, and pneumonia. The blood count needs to be monitored.

Obinotuzumab (Gazyva) is a humanized monoclonal antibody that targets CD20. It is administered intravenously and it is usually given in combination with chemotherapy (chlorambucil). The patients need to be premedicated and watched closely for possible infusion reaction. The blood pressure needs to be monitored. In patients with bulky disease, allopurinol and hydration precedes the infusion of the monoclonal antibody to avoid tumor lysis syndrome. This antibody can cause reactivation of past viral infections. Watch for bone marrow suppression.

Venetoclax is an anti BCL-2 oral medication that has been a breakthrough therapy for CLL patients with 17P deletion. As a single agent the response rate is 70%. It has been used also in combination with fludarabine or rituximab with an even better response rate.

The most common side effects are diarrhea, nausea, neutropenia, and upper respiratory infection. Watch for tumor lysis syndrome and pre medicate prior to infusing the drug with allopurinol and fluids.