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Treatment with ibrutinib, acalabrutinib for chronic lymphocytic leukemia may increase risk for second cancers

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David A. Bond

CHICAGO — Patients with chronic lymphocytic leukemia treated with either ibrutinib or acalabrutinib appeared at increased risk for second cancers, including lung cancer, prostate cancer and melanoma, according to data presented at ASCO Annual Meeting.

Additionally, patients with a history of smoking had higher rates of second cancers, study results showed.

“This emphasizes the importance of smoking cessation in patients with CLL in general and in those receiving ibrutinib or acalabrutinib, and reinforces the importance of overall routine cancer screening as part of the preventive care for patients with CLL,” David A. Bond, MD, oncologist in the division of hematology and medical oncology at The Ohio State University Comprehensive Cancer Center, told HemOnc Today.

It is well-known that patients with CLL are at increased risk for second cancers and that Bruton tyrosine kinase (BTK) inhibitors are highly effective in CLL. However, the effect of BTK inhibitors on the risk for and patterns of second cancers has not been established.

Bond and colleagues sought to determine the rate of and potential risk factors for second cancers among 691 patients (median age, 64 years; range, 24-91; 70% men; 94% white) with CLL receiving treatment with either ibrutinib (Imbruvica; Pharmacyclics, Janssen) or acalabrutinib (Calquence, AstraZeneca) — therapies that target the BTK protein and are highly effective and widely used for the treatment of CLL — compared with the general population. Patients received a median two prior lines of therapy; more than half (56%) were never smokers.

After median follow-up of 44 months, 20% of patients were diagnosed with nonmelanoma skin cancer, 9% with other secondary invasive cancers, and 8% with Richter’s transformation. Cumulative incidence of nonmelanoma skin cancer was 7.5% (95% CI, 5.7-9.7) at 1 year, 15.6% (95% CI, 12.8-18.5) at 3 years, and 23% (95% CI, 19.2-27.1) at 5 years.

Results of a multivariate analysis showed smoking (HR = 2.77; 95% CI, 1.61-4.78) and low baseline CD8 count (HR = 0.87 for twofold increase; 95% CI, 0.81-0.93) both appeared associated with higher risk for second cancers.

“This was surprising, as CD8 count had not been previously demonstrated in patients with CLL,” Bond said. “This finding supports the importance of immune function as one of the major factors related to the higher cancer rate in patients with CLL.”

Researchers estimated a 3-year OS rate of 79% (95% CI, 76-82). Factors associated with death included CLL/Richter’s transformation (38%), second cancer excluding Richter’s transformation (13%), infection (13%), cardiovascular disease (4%) and other causes (13%).

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“This study shows that patients receiving ibrutinib or acalabrutinib for CLL continue to have an increased risk for second cancers, but does not answer what, if any, effect ibrutinib or acalabrutinib have on that risk,” Bond said. “This question may be better answered by comparing rates for second cancers from patients enrolled in large prospective clinical trials of ibrutinib or acalabrutinib vs. patients treated with other therapies.”

Bond said subsequent research should help address whether any additional screening interventions could be recommended to improve early detection of specific second cancers for all patients with CLL. – by Jennifer Southall

Reference:

Bond D, et al. Abstract 7511. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: Bond reports no relevant financial disclosures. Please see abstract for all other authors’ relevant financial disclosures.