Quality of Life in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Improves after Minimal Residual Disease-Guided Treatment with Ibrutinib Plus Venetoclax
- Receipt of grants/research supports Abbvie
Improving health-related quality of life (HRQoL) is a critical treatment objective for patients with chronic lymphocytic leukemia (CLL). 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.
The HRQoL of RR CLL patients was assessed in the HOVON 141/Vision study as a pre-planned analysis. HRQoL was evaluated through EORTC QLQ-C30 and QLQ-CLL16 questionnaires at baseline, after 15 cycles IV, and at 6 months, 1, 2, and 3 years after end of induction treatment (EOIT). Minimal important differences (MID) were used to determine clinically meaningful changes.
224 patients were included, with a mean GHS of 66/100. After 15 cycles of IV, most patients reported clinically relevant improvements (44%) or stable GHS (41%), while 15% showed clinically significant decline in GHS. Mean GHS improved by +10 (95% CI +7 to +13), with a notable decrease in future health concerns of -12 (95% CI -8 to -16).
Six months after EOIT, clinically relevant improvements in GHS (+11; 95% CI 8 to 14), fatigue (-12; 95% CI -9 to -15), disease-related symptoms (-12; 95% CI -10 to -14), and future health worries (-17; 95% CI -13 to -21) were observed compared to baseline, with effects lasting up to three years. A transient increase in treatment-related symptoms was noted at EOIT (+8; 95% CI 5 to 11 and +14; 95% CI 10 to 18, respectively), but these scores returned to baseline six months after EOIT in all treatment groups.
After induction, 72 patients with undetectable MRD were randomized: 24 received ibrutinib maintenance and 48 underwent treatment cessation, while the others continued ibrutinib monotherapy, Clinically relevant improvements were noted one year post-IV compared to baseline: in the uMRD I arm, GHS (+9), role functioning (+16), emotional functioning (+9), cognitive functioning (+7), and future health worries (-17). In the uMRD cessation arm, GHS improved by +11, with reductions in fatigue (-14), disease-related symptoms (-12), and future health worries (-15). The I continuation arm showed improvements in GHS (+12), physical functioning (+6), role functioning (+11), fatigue (-15), dyspnea (-15), disease-related symptoms (-14), and future health worries (-17).
MRD-guided treatment with IV significantly impoves HRQoL in RR CLL, reducing fatigue, disease-related symptoms, and health concerns. These benefits persist for at least three years post-induction. Clinically relevant improvements in GHS and health concerns occur in both patients continuing ibrutinib and those who cease treatment. Overall, MRD-guided IV therapy provides substantial HRQoL benefits alongside its established high efficacy.