The Impact of Fitness and Dose Intensity on Safety and Efficacy Outcomes after Venetoclax-Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.4639-4639
• Main Authors: Al-Sawaf, Othman, Fürstenau, Moritz, Giza, Adam, Robrecht, Sandra, Von Tresckow, Julia, Fink, Anna Maria, Simon, Florian, Tausch, Eugen, Schneider, Christof, Sivcheva, Liliya, Schwarer, Anthony, Loscertales, Javier, Weinkove, Robert, Strumberg, Dirk, Kilfoyle, Allanah R., Juliusson, Gunnar, Da Cunha-Bang, Caspar, Illmer, Thomas, Gregor, Michael, Thornton, Patrick, Janssens, Ann, Tadmor, Tamar, Lindström, Vesa, Staber, Philipp Bernhard, Levin, Mark-David, Wendtner, Clemens-Martin, Kreuzer, Karl-Anton, Ritgen, Matthias, Stilgenbauer, Stephan, Kater, Arnon P., Niemann, Carsten Utoft, Fischer, Kirsten, Eichhorst, Barbara F., Hallek, Michael
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-188827

Introduction Following the results of two phase-III studies, the CLL14 study, recruiting elderly and unfit patients (pts) with chronic lymphocytic leukemia (CLL), and the CLL13 study, recruiting younger and fit pts, venetoclax-obinutuzumab (Ven-Obi) is a standard of care for pts with treatment-naive CLL. However, it is unclear whether age and/or fitness have an impact on the tolerability and efficacy of Ven-Obi. Furthermore, the impact of dose reductions on response and survival has not been explored yet. Here, we present a pooled analysis detailing the toxicity and efficacy of Ven-Obi in pts treated within the CLL13 and CLL14 studies. Methods Patients randomized to the Ven-Obi arm in CLL14 (2015-2016) and CLL13 (2016-2019) with at least one dose of study drug were considered and categorized as fit or unfit pts (cumulative illness rating scale [CIRS] > 6 and/or creatinine clearance < 70 ml/min). Patients with TP53 aberrations were excluded to ensure balanced features across the CLL13 and CLL14 populations. Correlations regarding minimal residual disease (MRD) in peripheral blood and response (both assessed at the end of treatment [EOT]) were assessed by chi² test. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier methodology and Cox proportional hazard regression modeling. Dose intensity was calculated as the relative fraction within the administered treatment cycles (excluding pts with treatment discontinuation due to PD/death). Adverse events were analyzed up to 28 days after EOT. Results In total, 410 pts were considered for this analysis, 228 from CLL13 and 182 from CLL14. The median observation time was 49 months (interquartile range [IQR] 37.0-65.8 months); for CLL13, median observation time was 38.9 months (IQR 33.8-46.3), and 66.7 months in CLL14 (IQR 64.4-70.8). Median age at enrollment was 67 years (IQR 58-73); 55.7% were grouped as unfit (median age 72), 44.3% as fit (median age 58) ( A). Overall response rate (ORR) was 89.5% in unfit and 96.1% in fit pts (p=0.011), CR rates were 51.8% and 54.1% (p=0.63), respectively. The undetectable MRD (