Temporary cessation of ibrutinib results in reduced grade 3‐4 infections and durable remissions—Interim analysis of an on‐off‐repeat Phase 1b/2 study in patients with chronic lymphocytic leukemia

Abstract

Ibrutinib is used continuously in CLL. This phase 1b/2 study interim analysis explored on‐off‐repeat dosing to reduce toxicity. After 12 months, 16/22 patients (73%) remained in first off‐phase irrespective if initial CR/PR or TP53 aberration. Grade 3‐4 infections were reduced from 55% to 5% during a similarly long off‐phase (P < .01). Treg and exhausted T‐cells increased (P = .01). Six patients restarted ibrutinib at early progression and remain drug‐sensitive. Our interim analysis shows a durable off‐phase in most patients, with reduced infections and cost‐saving potential. If toxicity‐driven permanent cessation of ibrutinib will be affected will be explored in the extended study.

Systemic and mucosal adaptive immunity to SARS-CoV-2 during the Omicron wave in patients with chronic lymphocytic leukemia

“…Further studies are required on how the generally low neutralization capacity of saliva Abs affects the risk of re-infection, if receiving BTKi/BCL-2i therapy adds to this risk, and if our ndings in BTKi-treated patients may be relevant also for other pathogens. Of note, the risk of grade 3-4 bacterial infections, mainly pneumonias, was markedly reduced if BTKi treatment was put on hold in patients with CLL (37).…”

Systemic and mucosal adaptive immunity to SARS-CoV-2 during the Omicron wave in patients with chronic lymphocytic leukemia

“…Notably, a significant reduction in the risk of grade 3-4 bacterial infections, mainly pneumonia, has been reported when the administration of BTKi is temporarily ceased in patients with CLL. 15 This observation suggests a more widespread impairment of mucosal immunity post-BTKi, which also extends to other pathogens.…”