Infection Risk as a Driver of Frontline Treatment Selection in Chronic Lymphocytic Leukemia

Danielle M. Brander, MD, of Duke University School of Medicine, and Marc J. Braunstein, MD, PhD, of NYU Grossman Long Island School of Medicine, examine infection as a leading competing risk in chronic lymphocytic leukemia (CLL). They review registry data showing nearly half of patients develop a serious infection and infection contributes to almost a third of deaths, the immune defects intrinsic to CLL, and the 6-to-12-month window of vulnerability after fixed-duration therapy ends. They compare infection rates across AMPLIFY (serious or grade 3 or higher infection in 14% with acalabrutinib plus venetoclax vs 25% with the triplet adding obinutuzumab), ELEVATE-TN, and CLL14 (grade 3 or 4 infection in 17.5% vs 15%), and note similar serious infection rates near 30% across BTK inhibitors in ELEVATE-RR and ALPINE. Dr Braunstein favors continuous therapy for unmutated IGHV and TP53-aberrant disease and urges counseling patients that infection is the key risk of chemotherapy-free regimens.