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:10.1002/jha2.261

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

EJHaem. 2021 Jul 14;2(3):525-529. doi: 10.1002/jha2.261. eCollection 2021 Aug.

Authors

Jeanette Lundin^{1

2}, Tom A Mulder¹, Magdalena Kättström³, Tove Wästerlid^{2

4}, Anders Uddevik⁵, Håkan Mellstedt¹, Kia Heimersson¹, Lotta Hansson^{1

2}, Marzia Palma^{1

2}, Anders Österborg^{1

2}

Affiliations

¹ Department of Oncology-Pathology Karolinska Institutet Stockholm Sweden.
² Lymphoma Unit, Department of Hematology Karolinska University Hospital Solna Stockholm Sweden.
³ Department of Medicine, Section of Hematology Örebro University Hospital Örebro Sweden.
⁴ Division of Clinical Epidemiology, Department of Medicine Solna Karolinska Institutet Stockholm Sweden.
⁵ Department of Medicine, Section of Hematology Gävle Hospital Gävle Sweden.

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.