eJHaem (Aug 2021)

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

  • Jeanette Lundin,
  • Tom A. Mulder,
  • Magdalena Kättström,
  • Tove Wästerlid,
  • Anders Uddevik,
  • Håkan Mellstedt,
  • Kia Heimersson,
  • Lotta Hansson,
  • Marzia Palma,
  • Anders Österborg

DOI
https://doi.org/10.1002/jha2.261
Journal volume & issue
Vol. 2, no. 3
pp. 525 – 529

Abstract

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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.