Cessation of ibrutinib results in reduced infections and durable remissionsfirst analysis of an on-off-repeat study in patients with chronic lymphocytic leukemia

ABSTRACT

Ibrutinib is used continuously in CLL. This phase 1b trial (n=22) explored on-off-repeat dosing to reduce toxicity and costs. After 12 months, 73% remained in the first off-phase irrespective if initial CR/PR or TP53 aberration. Reduced/eliminated hematomas, nail/skin changes, and notably, grade 3-4 infections (from 55% in the year before to 5% during similarly long off-phase) were observed (all p<0.01). Increased Treg and exhausted T-cells (p=0.01) were observed. Six patients restarted ibrutinib at early progression and all remain drug-sensitive. Conclusion: Withholding ibrutinib appears safe and switching on BTK-signaling should be explored to improve covid-19 vaccine efficacy while reducing infections and side effects.