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
Affiliations
Jeanette Lundin
Department of Oncology‐Pathology Karolinska Institutet Stockholm Sweden
Tom A. Mulder
Department of Oncology‐Pathology Karolinska Institutet Stockholm Sweden
Magdalena Kättström
Department of Medicine, Section of Hematology Örebro University Hospital Örebro Sweden
Tove Wästerlid
Lymphoma Unit, Department of Hematology Karolinska University Hospital Solna Stockholm Sweden
Anders Uddevik
Department of Medicine, Section of Hematology Gävle Hospital Gävle Sweden
Håkan Mellstedt
Department of Oncology‐Pathology Karolinska Institutet Stockholm Sweden
Kia Heimersson
Department of Oncology‐Pathology Karolinska Institutet Stockholm Sweden
Lotta Hansson
Department of Oncology‐Pathology Karolinska Institutet Stockholm Sweden
Marzia Palma
Department of Oncology‐Pathology Karolinska Institutet Stockholm Sweden
Anders Österborg
Department of Oncology‐Pathology Karolinska Institutet Stockholm 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.
