High karyotypic complexity is an independent prognostic factor in patients with CLL treated with venetoclax combinations

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Moritz Fürstenau
  • Yvonne J. Thus
  • Sandra Robrecht
  • Clemens H.M. Mellink
  • Anne Marie van der Kevie-Kersemaekers
  • Julie Dubois
  • Julia von Tresckow
  • Michaela Patz
  • Michael Gregor
  • Patrick Thornton
  • Philipp B. Staber
  • Tamar Tadmor
  • Mark David Levin
  • Caspar da Cunha-Bang
  • Christof Schneider
  • Thomas Illmer
  • Björn Schöttker
  • Ann Janssens
  • Ilse Christiansen
  • Thomas Nösslinger
  • Michael Baumann
  • Holger Hebart
  • Tobias Gaska
  • Josien C. Regelink
  • Ellen C. Dompeling
  • Vesa Lindström
  • Gunnar Juliusson
  • Anouk Widmer
  • Jeroen Goede
  • Neta Goldschmidt
  • Florian Simon
  • Nisha De Silva
  • Anna Maria Fink
  • Kirsten Fischer
  • Clemens Martin Wendtner
  • Matthias Ritgen
  • Monika Brüggemann
  • Eugen Tausch
  • Marcel Spaargaren
  • Eric Eldering
  • Stephan Stilgenbauer
  • Michael Hallek
  • Barbara Eichhorst
  • Karl Anton Kreuzer
  • Arnon P. Kater
Complex karyotypes have been associated with inferior outcomes in chronic lymphocytic leukemia (CLL) treated with chemoimmunotherapy (CIT) while their prognostic impact in the context of venetoclax-based treatments is still debated. In this prospective analysis on karyotype complexity in CLL, we evaluated the impact of complex (≥3 chromosomal aberrations [CA], CKT) and highly complex karyotypes (≥5 CA, hCKT) as well as specific aberrations in previously untreated patients without TP53 aberrations undergoing either CIT or time-limited venetoclax-based therapies in the phase 3 GAIA/CLL13 trial. Karyotype analyses were available for 895 of 926 (96.7%) patients of whom 153 (17%) had a CKT and 43 (5%) hCKT. In the CIT arm, CKT was associated with shorter PFS (HR 2.58, 95%CI 1.54-4.32, p<0.001) and OS (HR 3.25, 95%CI 1.03-10.26, p=0.044). In the pooled venetoclax arms a multivariable analysis identified hCKT (HR 1.96, 95%CI 1.03-3.72, p=0.041) but not CKT as independent adverse prognosticators for PFS. The presence of translocations (unbalanced and/or balanced) was also independently associated with shorter PFS in the venetoclax arms. CIT led to the acquisition of additional CA (mean CA: 2.0 to 3.4, baseline to CLL progression) while karyotype complexity remained stable after venetoclax-based treatments (2.0, both time points). This analysis establishes highly complex karyotypes and translocations as adverse prognostic factors in the context of venetoclax-based combination treatments. The findings of this study support the incorporation of karyotyping into the standard diagnostic work-up of CLL as it identifies patients at high risk for poor treatment outcomes and thereby improves prognostication.
Udgave nummer5
Sider (fra-til)446–459
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The trial was sponsored by the German CLL Study Group with financial support and study drug provision from Roche , AbbVie , and Janssen . This analysis was partly supported by a Dutch Cancer Foundation grant (Coherent: 13650/2021-Infra).

Publisher Copyright:
© 2023 The American Society of Hematology

ID: 360173586