New Targeted Therapies for CLL and Autoimmune Complications

Of the more than 20,700 people who are diagnosed with chronic lymphocytic leukemia (CLL) in the United States each year,¹ approximately 1 in 4 also have autoimmune complications.² Some of the most significant of these complications are autoimmune cytopenias, in which the body has an immune reaction against itself that results in low blood-cell counts.³ Examples of common autoimmune cytopenias are autoimmune hemolytic anemia (resulting in low numbers of red blood cells) and immune thrombocytopenia (leading to low numbers of platelets).²

Because patients with CLL can have autoimmune cytopenias, researchers wanted to find out if using a targeted therapy affects autoimmune cytopenias in patients who already have them, and if patients who use a targeted drug have autoimmune cytopenias as a side effect.³ Researchers focused on 3 newer drugs that are often used for treatment of patients with CLL—including ibrutinib (Ibruvica), idelalisib (Zydelig), and venetoclax (Venclexta). They compared these 3 oral drugs, which are effective for the treatment of CLL, with the current standard chemoimmunotherapy, to understand their effect on autoimmune cytopenia.³

After reviewing the evidence, the researchers concluded that each of these 3 targeted drugs affects autoimmune cytopenias in a different way.³ Among these 3 CLL treatments, ibrutinib has the most evidence showing that it can improve pre-existing autoimmune cytopenias. Ibrutinib can cause new autoimmune cytopenias during the first few weeks of treatment, but over time, it has lower rates of autoimmune cytopenias.^2,3

Idelalisib does not cause autoimmune cytopenias, but its use can lead to other types of autoimmune complications, including inflammation of the lungs (pneumonitis), increases in liver enzyme levels (transaminitis), and inflammation of the large intestine (colitis). Healthcare providers and patients need to know how to recognize the warning signs of these autoimmune complications that are nonhematologic events. Doctors can prescribe steroids and/or a break from using idelalisib if these types of autoimmune reactions occur.³

Venetoclax is one of the newest targeted drugs for CLL. Researchers found that treatment-related autoimmune cytopenias can happen with venetoclax. However, because the follow-up time in clinical trials of venetoclax is short, it is not clear what effect the drug has on the treatment of existing autoimmune complications. To date, no studies of venetoclax have reported nonhematologic autoimmune complications (such as colitis or pneumonitis).³

This study was the first effort to fully understand the impact of ibrutinib, idelalisib, and venetoclax on autoimmune complications. As longer-term data for these newer targeted drugs become available, oncologists and researchers will have better understanding how to identify and manage autoimmune complications in patients with CLL.

References

1. Siegel RL, Miller KD, Jemal A. Cancer statistics. 2019. CA: A Cancer Journal for Clinicians. 2019;69:7-34.
2. Hamblin TJ. Autoimmune complications of chronic lymphocytic leukemia. Seminars in Oncology. 2006;33:230-239.
3. Vitale C, Montalbano MC, Salvetti C, et al. Autoimmune complications in chronic lymphocytic leukemia in the era of targeted drugs. Cancers. 2020;12:282.
4. Kaltwasser J. Wave of targeted CLL therapies raises questions about autoimmune complications. American Journal of Managed Care Leukemia and Lymphoma News. February 4, 2020. www.ajmc.com/newsroom/wave-of-targeted-cll-therapies-raises-questions-about-autoimmune-complications. Accessed February 29, 2020.