Time-limited treatment with ibrutinib plus venetoclax in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) guided by measurable residual disease (MRD) significantly improves quality of life (QoL) for these patients, including mitigating fatigue. The patients saw clinically relevant improvements at the end of their combination therapy course, including a 10-point improvement in global health status (GHS), a 12-point decrease in future health worries, a 16-point improvement in role functioning, and a 7-point improvement in cognitive functioning, from baseline. The full results of the study were presented at the 66th American Society of Hematology Annual Meeting and Exposition.
“Patients’ QoL improves after treatment with venetoclax and ibrutinib,” presenting author Laura Elisabeth Maria Eurelings, MD, PhD, of the Albert Schweitzer Hospital in Dordrecht, Netherlands, told ASH Clinical News. “This improvement is durable for up to three years after treatment with the combination. Although patients do experience side effects and treatment-related symptoms, the improvements in the global health status, their fatigue, and disease-related symptoms outweigh these negative effects of treatment. Moreover, after cessation of venetoclax, treatment-related symptoms return to the values recorded for patients before treatment was started.”
Dr. Eurelings and her colleagues analyzed the health-related QoL data from the phase II HOVON 141/VISION Europe-based trial in which patients with R/R CLL were treated with 15 cycles of ibrutinib and venetoclax following a short induction with ibrutinib. The treatment on study was guided by MRD measurements, and no patient with undetectable MRD (uMRD) progressed on study after treatment cessation. Of the patients on study, 224 completed at least one questionnaire and were included in the analysis. Patients were a median age of 69 years, and 70% were male.
The 72 patients who reached uMRD status after 15 cycles were randomized 1:2 to continue ibrutinib maintenance therapy (n=24) or stop treatment (n=48). Patients with uMRD continued to be followed and were retested for MRD status. Patients who became positive for MRD after stopping the combination therapy were retreated on ibrutinib plus venetoclax therapy followed by ibrutinib maintenance.
The primary endpoint was 12-month progression-free survival (PFS) after randomization. The 12-month PFS in the treatment cessation group was 98%; 96% among those who were MRD negative and continued on ibrutinib therapy; and 97% among those who were MRD positive and continued on ibrutinib therapy.2
To assess QoL, Dr. Eurelings and her colleagues evaluated changes in functioning scales, including global health status (GHS)/QoL, and also assessed symptoms using the EORTC QLQ-C30 and QLQ-CLL16 questionnaires, completed by patients at baseline, the end of the combination therapy after cycle 15, at six months, and one, two, and three years after cycle 15. Symptoms that researchers inquired about included diarrhea, constipation, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, fatigue, and financial difficulties.
At six months after induction therapy, there was a clinically relevant improvement of a median of 11 points in the GHS, a decrease in fatigue by a median of 12 points, a 12-point median decrease in disease-related symptoms, and a 17-point median decrease in “future health worries” compared with baseline. These effects persisted until three years after the end of induction therapy. There was a short-term increase in treatment-related symptoms and diarrhea; however, these symptoms’ scores returned to baseline scores six months after the end of induction therapy in each treatment group.
Overall, patients treated with ibrutinib plus venetoclax experienced clinically relevant improvements in health-related QoL. Additionally, those patients who discontinued ibrutinib based on MRD status showed improvements in scores more often compared with patients who continued ibrutinib.
“There have been improvements in patients’ survival due to advances in treatment options, but unfortunately, CLL remains an incurable disease. Preserving QoL is therefore a main goal of treatment,” Dr. Eurelings said. “Our study is the first to examine in depth the effect of the combination of venetoclax and ibrutinib on the QoL of patients with R/R CLL.”
“Now, more and more CLL trials are investigating QoL among patients with CLL,” Dr. Eurelings added. “Investigating QoL is an important step to help aid clinicians and patients in selecting the optimal treatment regimen. Not only effectiveness, safety, and side effects but also QoL improvements and how quickly the QoL improves after starting treatment should be considered. Furthermore, information on the effect of treatment on QoL is important in informing patients about what to expect when starting treatment.”
Any conflicts of interest declared by the authors can be found in the original abstract.
References
1. Eurelings LEM, Rotbain EC, Kersting S, et al. Quality of life in patients with relapsed/refractory chronic lymphocytic leukemia improves after minimal residual disease-guided treatment with ibrutinib plus venetoclax. Abstract 888. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 9, 2024; San Diego, California.
2. Kater AP, Levin MD, Dubois J, et al. Minimal residual disease-guided stop and start of venetoclax plus ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia (HOVON141/VISION): primary analysis of an open-label, randomised, phase 2 trial. Lancet Oncol. 2022;23(6):818-828.
