Quality of Life in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Improves after Minimal Residual Disease-Guided Treatment with Ibrutinib Plus Venetoclax

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.888-888
• Main Authors: Eurelings, Laura Elisabeth Maria, Rotbain, Emelie Curovic, Kersting, Sabina, Van Der Straten, Lina, Enggaard, Lisbeth, Veldhuis, Gerrit Jan, Mous, Rogier, Poulsen, Christian Bjørn, Frederiksen, Henrik, Janssens, Ann, Schjoedt, Ida, Dompeling, Ellen C, Ranti, Juha, Brieghel, Christian, Mattsson, Mattias, Bellido, Mar, Tran, Hoa T, Stege, Claudia A M, Nasserinejad, Kazem, Kater, Arnon P., Niemann, Carsten Utoft, Levin, Mark-David
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-211226

Introduction: Improving health-related quality of life (HRQoL) is a critical treatment objective for patients with chronic lymphocytic leukemia (CLL) due to its incurable nature. The HOVON 141/Vision trial has demonstrated high efficacy for MRD-guided, time-limited treatment with ibrutinib plus venetoclax (IV) in patients with relapsed or refractory (RR) CLL. However, data on the impact of MRD-guided IV on HRQoL remain limited. Methods: Assessment of HRQoL in patients with RR CLL was conducted within the framework of the HOVON 141/Vision study as a pre-planned analysis. RR CLL patients were treated with IV for 15 cycles. In patients with detectable MRD (≥10-4), I was continued, while patients with undetectable MRD (uMRD in blood and bone marrow, < 10-4) were randomized 1:2 for I maintenance or treatment cessation. Upon MRD recurrence in the treatment cessation arm, IV was reinitiated followed by I maintenance (Niemann 2024). Changes in functioning scales, global health status (GHS)/QoL, and symptoms were assessed using the EORTC QLQ-C30 and QLQ-CLL16 questionnaires, completed at baseline, the end of IV (cycle 15), and at 6 months, 1, 2, and 3 years after cycle 15. Minimal important differences (MID) were used to determine whether changes in scores are clinically meaningful. MIDs were calculated using a distribution-based approach (van der Straten, Blood 2023). Results: 224 patients completed at least one questionnaire and were included in the analysis. At baseline, the mean GHS of the full cohort was 66. After 15 cycles of IV, the majority of patients reported clinically relevant improvement (positive change in score >8, the MID) or stable GHS (change between +8 and -8) (44% and 41% respectively), while 15% showed a clinically relevant decrease in GHS (negative change in score >8, the MID). A clinically relevant improvement in the mean GHS was observed after 15 cycles of IV (+10; 95% CI +7 to +13). Similarly, a clinically relevant decrease in future health concerns was observed (-12; 95% CI -8 to -16). After induction treatment, 72 patients with uMRD were randomly assigned to a treatment group, 24 to ibrutinib maintenance (uMRD I) and 48 to treatment cessation (uMRD cessation). The remaining patients continued with ibrutinib monotherapy (I continuation). One year after the end of induction (EOIT) treatment, the majority of patients reported a clinically relevant improvement or stable GHS: 24% and 57% for uMRD I, 22% and 65% for uMRD cessation, and 21% and