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The impact of fitness and dose intensity on clinical outcomes with venetoclax-obinutuzumab in CLL

Al-Sawaf, Othman ; Fürstenau, Moritz ; Giza, Adam ; Robrecht, Sandra ; von Tresckow, Julia ; Fink, Anna Maria ; Simon, Florian ; Tausch, Eugen ; Schneider, Christof and Sivcheva, Liliya , et al. (2025) In Blood
Abstract

Venetoclax-obinutuzumab (Ven-Obi) is a standard first-line therapy for chronic lymphocytic leukemia (CLL). The impact of age, fitness, and dose reductions remains unclear. We analyzed patients treated with Ven-Obi in the CLL13 and CLL14 trials, excluding patients with TP53 aberrations. Fitness was assessed using the cumulative illness rating scale (CIRS, >6) and creatinine clearance (≤70 mL/min). Among 410 patients (median age, 67 years), 55.7% were unfit (median age, 72 years) and 44.3% were fit (median age, 58 years). Overall response rate (ORR) was 89.5% in unfit and 96.1% in fit patients. Rates of undetectable minimal residual disease (uMRD) at <10–4were 80.3% in unfit and 85.1% in fit patients.... (More)

Venetoclax-obinutuzumab (Ven-Obi) is a standard first-line therapy for chronic lymphocytic leukemia (CLL). The impact of age, fitness, and dose reductions remains unclear. We analyzed patients treated with Ven-Obi in the CLL13 and CLL14 trials, excluding patients with TP53 aberrations. Fitness was assessed using the cumulative illness rating scale (CIRS, >6) and creatinine clearance (≤70 mL/min). Among 410 patients (median age, 67 years), 55.7% were unfit (median age, 72 years) and 44.3% were fit (median age, 58 years). Overall response rate (ORR) was 89.5% in unfit and 96.1% in fit patients. Rates of undetectable minimal residual disease (uMRD) at <10–4were 80.3% in unfit and 85.1% in fit patients. Progression-free survival (PFS) at 3 years was 86.4% vs 87.5% (hazard ratio, [HR], 1.12; 95% confidence interval [CI], 0.70-1.81; P = .63). Overall survival at 3 years was 91.8% vs 96.9% (HR, 2.02; 95% CI, 0.90-4.55; P = .088). Adverse events included neutropenia (62.7% unfit, 56.9% fit), infusion-related-reactions (44.3% unfit, 56.9% fit), fatigue (15.8% unfit, 35.9% fit), and infections (57.5% unfit, 69.6% fit). Venetoclax dose reductions of <80% occurred in 39.6% of unfit and 17.6% of fit patients, with lower ORR (83.3% vs 98.2%) and uMRD rates (74.2% vs 87.9%) in those with reduced dose intensities, but similar PFS. Dose reductions of <70% were associated with shorter PFS. Overall, this study shows comparable efficacy and toxicity of Ven-Obi in fit and unfit patients with CLL.

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Contribution to journal
publication status
epub
subject
in
Blood
publisher
American Society of Hematology
external identifiers
  • pmid:40864973
  • scopus:105017664984
ISSN
0006-4971
DOI
10.1182/blood.2025028899
language
English
LU publication?
yes
id
30cffbea-4ddb-47f0-9f48-7a8494526fe5
date added to LUP
2025-12-08 11:35:59
date last changed
2025-12-08 11:37:02
@article{30cffbea-4ddb-47f0-9f48-7a8494526fe5,
  abstract     = {{<p>Venetoclax-obinutuzumab (Ven-Obi) is a standard first-line therapy for chronic lymphocytic leukemia (CLL). The impact of age, fitness, and dose reductions remains unclear. We analyzed patients treated with Ven-Obi in the CLL13 and CLL14 trials, excluding patients with TP53 aberrations. Fitness was assessed using the cumulative illness rating scale (CIRS, &amp;gt;6) and creatinine clearance (≤70 mL/min). Among 410 patients (median age, 67 years), 55.7% were unfit (median age, 72 years) and 44.3% were fit (median age, 58 years). Overall response rate (ORR) was 89.5% in unfit and 96.1% in fit patients. Rates of undetectable minimal residual disease (uMRD) at &amp;lt;10<sup>–4</sup>were 80.3% in unfit and 85.1% in fit patients. Progression-free survival (PFS) at 3 years was 86.4% vs 87.5% (hazard ratio, [HR], 1.12; 95% confidence interval [CI], 0.70-1.81; P = .63). Overall survival at 3 years was 91.8% vs 96.9% (HR, 2.02; 95% CI, 0.90-4.55; P = .088). Adverse events included neutropenia (62.7% unfit, 56.9% fit), infusion-related-reactions (44.3% unfit, 56.9% fit), fatigue (15.8% unfit, 35.9% fit), and infections (57.5% unfit, 69.6% fit). Venetoclax dose reductions of &amp;lt;80% occurred in 39.6% of unfit and 17.6% of fit patients, with lower ORR (83.3% vs 98.2%) and uMRD rates (74.2% vs 87.9%) in those with reduced dose intensities, but similar PFS. Dose reductions of &amp;lt;70% were associated with shorter PFS. Overall, this study shows comparable efficacy and toxicity of Ven-Obi in fit and unfit patients with CLL.</p>}},
  author       = {{Al-Sawaf, Othman and Fürstenau, Moritz and Giza, Adam and Robrecht, Sandra and von Tresckow, Julia and Fink, Anna Maria and Simon, Florian and Tausch, Eugen and Schneider, Christof and Sivcheva, Liliya and Schwarer, Anthony and Loscertales, Javier and Weinkove, Robert and Strumberg, Dirk and Kilfoyle, Allanah and Juliusson, Gunnar and da Cunha-Bang, Caspar and Illmer, Thomas and Gregor, Michael and Thornton, Patrick and Janssens, Ann and Tadmor, Tamar and Lindström, Vesa and Staber, Philipp and Levin, Mark David and Wendtner, Clemens Martin and Kreuzer, Karl Anton and Ritgen, Matthias and Stilgenbauer, Stephan and Kater, Arnon P. and Niemann, Carsten and Fischer, Kirsten and Eichhorst, Barbara and Hallek, Michael}},
  issn         = {{0006-4971}},
  language     = {{eng}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{The impact of fitness and dose intensity on clinical outcomes with venetoclax-obinutuzumab in CLL}},
  url          = {{http://dx.doi.org/10.1182/blood.2025028899}},
  doi          = {{10.1182/blood.2025028899}},
  year         = {{2025}},
}