Therefore, they evaluated this association in their patient population. The estimated cumulative risk for developing AF was 14% at 60 months. Baseline levels of HDL did not predict for AF risk. However, Dr Molica and colleagues observed that after 12 months of therapy with ibrutinib, when the risk for developing AF decreases, concentrations of HDL levels were significantly increased.

“This suggests a potentially favorable effect of long-term therapy with ibrutinib on a modifiable risk factor of AF such as HDL concentration,” Dr Molica said.

On the whole, this is a very important topic, said Jing-Zhou Hou, MD, of UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, who noted that the discontinuation rate of ibrutinib is around 30% to 40%.

Generally, oncologists are not regularly monitoring patients for fasting glucose, triglycerides, or HDL levels. More commonly the focus is on the CLL and patients receive a complete blood count and measures of liver and kidney function. Glucose is monitored, but it is not fasting glucose, Dr Hou said.


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As mentioned, 8 patients with insulin-dependent type 2 diabetes prior to initiation of ibrutinib did not experience increase of insulin dose or fasting glucose level. The 3 out of 35 patients taking ibrutinib who developed type 2 diabetes had a family history of type 2 diabetes, and a higher median body mass index value. Dr Hou said that in this type of patient with preexisting risk factors for diabetes, it is a good idea to check fasting glucose prior to initiating ibrutinib therapy and to continue monitoring it or HbA1C level throughout the therapy.

“If the patient is tolerating the drug, you may choose to intervene or manage the hyperglycemia,” Dr Hou said. “If left untreated, hyperglycemia will generate long-term consequences down the road, particularly if you factor in the other potential adverse effects of the drug such as arrythmia and hypertension, which lead to an increased risk of cardiac events long-term.”

If these conditions cannot be managed on ibrutinib, there are alternative therapies for patients with cardiovascular complications, such as acalabrutinib, a second-generation Bruton kinase inhibitor.

“This is a good opportunity for patients to switch to an agent with similar activity but less toxic in terms of cardiovascular side effects,” Dr Molica said.

In fact, Dr Koch underscored the importance of our bodies to reach homeostasis by a proper stress response and mentioned a recently published paper in Science Immunology, which discusses the use of acalabrutinib in the treatment of patients with severe COVID-19 who have a hyperinflammatory immune response.2

“What is really interesting in the Science Immunology paper is that the mechanism of acalabrutinib involves also the impact on proinflammatory cytokines (IL-6, IL-12 etc), analogous to using the ‘hormone’ dexamethasone — which is anti-inflammatory — in COVID-19 patients,” Dr Koch said. “However, this works only in highly selective patients, and, of course, depends on the ‘proper stress response’ and correct timing of the disease course.”

References

  1. Molica S, Lentini M, Zappala D, Levato L. Effects of ibrutinib on glucose-lipid metabolism in patients with chronic lymphocytic leukemia (CLL) [published online June 16, 2020]. Leuk Lymphoma. doi: 10.1080.10428194.2020.1779258
  2. Roschewski M, Lionakis MS, Sharman JP, et al. Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Sci Immunol. 2020;5(48):eabd0110.