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BTK Inhibitor Yields Promising Results in CLL Resistant to Venetoclax
In assessing an alternative treatment to venetoclax for patients with relapsed or refractory chronic lymphocytic leukemia (CLL), researchers observed that patients with the BCL-2 Gly101Val venetoclax resistance mutation responded well to BTK inhibitor (BTKi) therapy (Blood. 2020;135[25]: 2266-2270).
“Results of prospective clinical trials demonstrate the efficacy of venetoclax to salvage patients with disease progression on BTKis, but data on BTKi therapy after disease progression on venetoclax are limited,” wrote Victor S. Lin, MD, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, Australia, and colleagues.
Dr Lin et al evaluated 23 patients with relapsed or refractory CLL who received BTKi therapy (ibrutinib, n = 21; zanubrutinib, n = 2) after stopping venetoclax because of resistance to the drug.
After the use of BTKi therapy, the median progression-free survival (PFS) was 34 months and the median overall survival was 42 months. Prior remission duration and attainment of complete remission on venetoclax were associated with longer PFS after BTKi salvage therapy (P = 0.44 and P = .029, respectively).
BTKi therapy for patients with venetoclax resistance yielded durable benefit with an estimated PFS of 24 months. At 33 months, 11 patients were still receiving BTKi therapy; the other 12 had stopped therapy because of disease progression (n = 8) or toxicity (n = 4).
“Our findings indicate that BTKi therapy can provide durable CLL control after disease progression on venetoclax,” concluded Dr Lin et al.—Alexandra Graziano
