BTK inhibitor therapy is effective in patients with CLL resistant to venetoclax
Mené à partir de données portant sur 23 patients atteints d’une leucémie lymphoïde chronique réfractaire ou récidivante, cette étude rétrospective évalue l’efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité des inhibiteurs de BTK (ibrutinib ou zanubrutinib) après l’échec d’un traitement par vénétoclax (durée médiane de suivi : 33 mois)
Highly active BTK inhibitors (BTKi) and the BCL2 inhibitor venetoclax have transformed the therapeutic landscape for chronic lymphocytic leukemia (CLL). Results of prospective clinical trials demonstrate the efficacy of venetoclax to salvage patients with disease progression on BTKi, but data on BTKi therapy following disease progression on venetoclax are limited, especially regarding durability of benefit. We retrospectively evaluated the records of 23 consecutive patients with relapsed/refractory CLL who received a BTKi (ibrutinib [n=21], zanubrutinib [n=2]) after ceasing venetoclax due to progressive disease. Median progression free survival and median overall survival after BTKi initiation were 34 (range <1-49) months and 42 (range 2-49) months respectively. Prior remission duration ?24 months and attainment of complete remission or undetectable measurable residual disease on venetoclax were associated with longer PFS after BTKi salvage (p=0.044 and p=0.029, respectively). BTKi therapy achieved durable benefit for patients with the BCL2 Gly101Val venetoclax resistance mutation (estimated 24-month PFS 69%). At a median survivor follow-up of 33 (range 2-53) months, 11 patients remain on BTKi and 12 have ceased therapy due to disease progression (n=8) or toxicity (n=4). Our findings indicate that BTKi therapy can provide durable CLL control after disease progression on venetoclax.
Blood 2020