Journal Article

DKFZ-2026-01495

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Ibrutinib in early stage CLL: Genetic risk factors and treatment outcome in the GCLLSG CLL12 trial.

Riecke, A. ; Robrecht, S. ; Yosifov, D.DKFZ* ; Schneider, C. ; Giza, A. ; Müller, L. ; Vehling-Kaiser, U. ; Eckart, M. J. ; Freier, W. ; Schöttker, B. ; Gaska, T. ; Reiser, M. ; Fink, A.-M. ; Fischer, K. ; Eichhorst, B. F. ; Hallek, M. J. ; Langerbeins, P. ; Stilgenbauer, S. ; Tausch, E.

2026
American Society of Hematology Washington, DC

Abstract: Watch & wait is the standard of care in asymptomatic early-stage chronic lymphocytic leukemia (CLL). The CLL12 trial investigated ibrutinib versus placebo in early-stage patients with intermediate to very high risk of progression, showing improved event-free survival (EFS) but no overall survival (OS) benefit10. Building on these findings, our analysis examined whether a significant benefit could be identified within distinct genetic subgroups. After a median follow-up of 69.3 months, there were 166 EFS and 32 OS events in 515 trial patients. In the placebo arm, del(17p), del(11q), +12, U-IGHV, and mutations in NOTCH1, ATM, NRAS/KRAS/BRAF, and NFKBIE correlated with shorter EFS. With ibrutinib, only del(17p) and TP53 and NFKBIE mutations significantly compromised EFS. Ibrutinib offered substantial EFS benefit in subgroups with U-IGHV, del(11q), +12, NOTCH1, ATM, and NFKBIE mutations. No EFS improvement was seen for asymptomatic early-stage patients with del(17p) or TP53 mutations. Ibrutinib provided no OS benefits in any genetic subgroup. Multivariable analysis revealed ibrutinib treatment as an independent favorable factor for EFS, while U-IGHV, del(17p), POT1, RAS/RAF, and NFKBIE mutations were adverse prognostic factors. The results confirm watch-and-wait as standard of care for early-stage CLL patients, especially in high-risk CLL characterized by del(17p) and/or mutated TP53. EudraCT Number: 2013-003211-22.

Note: epub

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Contributing Institute(s):

1. Mechanismen d. Leukämogenese (B061)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 20 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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