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Secondary Cancers and BTK Inhibitors for CLL

By: Celeste L. Dixon
Posted: Friday, August 9, 2019

Patients receiving the Bruton’s tyrosine kinase (BTK) inhibitors ibrutinib or acalabrutinib for chronic lymphocytic leukemia (CLL) should be intensively screened for the occurrence of non-melanoma skin cancer, Richter’s transformation, and secondary primary neoplasia, including melanoma, lung, prostate, and bladder cancers. Results of the retrospective study leading to this recommendation were presented at the 2019 American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract 7511).

David Alan Bond, MD, of The Ohio State University Comprehensive Cancer Center, Columbus, and colleagues noted that independent of treatment, patients with CLL are at increased risk for secondary primary neoplasia. Their study was designed to see whether treatment with BTK inhibitors increased the risk, while acknowledging that the agents “are highly effective in the treatment of CLL.” They analyzed the outcomes of 691 patients with CLL who were treated with ibrutinib or acalabrutinib (median age, 64 years), 56% of whom never smoked and 20% of whom were treatment-naive.

At 1, 3, and 5 years of follow-up, 7.8%, 15.8%, and 23.3% of patients, respectively, had developed non-melanoma skin cancer. The corresponding figures for patients who developed other secondary primary neoplasia were 2.1%, 7.6%, and 11.5%. From another statistical angle, at a median follow-up of 44 months, 68 patients (10%) had been diagnosed with secondary primary neoplasia (standard incidence ratio [SIR] = 2.4), including 13 lung (SIR = 3.2), 9 prostate (SIR = 1.4), 7 bladder cancers (SIR = 5.2), and 9 melanomas (SIR = 6.9). These ratios were calculated using the expected incidence rates from the Surveillance, Epidemiology, and End Results Program. Richter’s transformation was diagnosed in 58 patients (8%) and non-melanoma skin cancer, in 138 patients (20%).

“Smoking and low baseline CD8 count (P < .01 for both) were associated with [a] higher incidence of secondary primary neoplasia,” noted Dr. Bond and his team. The 3-year overall survival rate was 79%, and the most frequent causes of death were CLL/Richter’s transformation (57%) and secondary primary neoplasia (13%).

Disclosure: The study authors’ disclosure information may be found at coi.asco.org.



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