ASH 2025: Other Cancers in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

An estimated 1 in 8 people with chronic lymphocytic leukemia (CLL) or small cell leukemia (SLL) develop another type of cancer at some point during their lifetime. This may be partly the result of the cytotoxic effects of chemotherapy, and investigators were interested in understanding how the introduction of more targeted treatment options may have impacted the risk for other cancers. To this end, investigators analyzed the rates of other cancers in newly diagnosed patients with CLL/SLL. The results of this study were presented by Foundation Lymphoma Scientific Research Mentoring Program (LSRMP) scholar Helen Ma, MD, of VA Long Beach Healthcare System.

The study included outcomes from 6,844 people across multiple health systems in the United States, including the Department of Veteran Affairs (VA), MD Anderson Cancer Center, and the Mayo Clinic. Records were only included for patients newly diagnosed after January 1, 2016. Approximately one-third of patients received CLL-directed therapy, of which 77% received targeted therapy and 12% received chemoimmunotherapy (4% received combination targeted/chemoimmunotherapy and 6% received monoclonal antibody therapy only). The most common targeted therapies used were ibrutinib (50%), acalabrutinib (20%), and venetoclax (15%). 

A total of 583 people in the analysis were diagnosed with another cancer. The estimated risk was 4.2% at 24 months and 9.7% at 60 months. Risk for other cancers was found to be highest in older patients, males, and those who received CLL-directed therapies. Among the latter group, the risk was highest for those who received chemoimmunotherapy, with or without targeted therapy (60% increased risk relative to those who did not receive any CLL-directed therapy); however, patients who received targeted therapy only were still at elevated risk for other cancers relative to those who received no therapy for CLL (27%).

Based on these results, the investigators estimated that about 1 in 10 people with newly diagnosed CLL/SLL develop another cancer within 5 years. Although the risk is higher among people who received chemoimmunotherapy, there is still an elevated risk associated with targeted therapies for CLL.

This study also included contributions from former Foundation SAB member Susan O’Brien, MD of University of California, Irvine; and Foundation grantee Yucai, Wang, MD, PhD of Mayo Clinic, Rochester.