Health-related quality of life in patients with Waldenström macroglobulinemia: results from the ASPEN trial
Creators: name: Tedeschi, Alessandra
name: Tam, Constantine S
name: Owen, Roger G
name: Buske, Christian
name: Leblond, Véronique
name: Dimopoulos, Meletios
name: Garcia-Sanz, Ramón
name: Castillo, Jorge J
name: Trotman, Judith
name: Treon, Steven P
name: Yang, Keri
name: Tang, Boxiong
name: Allewelt, Heather
name: Patel, Sheel
name: Chan, Wai Y
name: Cohen, Aileen
name: Chen, Shengnan
name: Barnes, Gisoo
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Space Science
subject: Medicine
subject: Pharmacology
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Science Policy
subject: Mental Health
subject: Hematology

description: <b>Aim</b> ASPEN is a randomized, open-label, Phase III study comparing zanubrutinib and ibrutinib in patients with Waldenström macroglobulinemia (WM). <b>Materials &amp; methods:</b> Patient-reported outcomes were exploratory end points assessed using the EORTC QLQ-C30 and EQ-5D-5L VAS scores. <b>Results:</b> Overall, 201 patients (102 zanubrutinib; 99 ibrutinib) were enrolled. Clinically meaningful differences were observed in diarrhea and nausea/vomiting in both the intent-to-treat population and in patients attaining very good partial response (VGPR) in earlier cycles of treatment, as well as in long-term physical functioning and fatigue in patients achieving VGPR. <b>Conclusion:</b> Treatment with zanubrutinib was associated with greater improvements in health-related quality of life compared with ibrutinib in patients with WM and <i>MYD88</i> mutations. <b>Clinical Trial Registration:</b>NCT03053440 (ClinicalTrials.gov) <b>Patient quality of life is important</b> This article talks about a study called the ASPEN trial, which compares two medicines used for treating a rare blood cancer that doctors call Waldenström macroglobulinemia. The medicines are called zanubrutinib (ZAN) and ibrutinib (IBR). They work in the same way, by blocking a protein called Bruton tyrosine kinase. When patients take medicines for an illness, it is important to learn about their physical, social, emotional and mental well-being (quality of life). In this study, we asked patients to fill out questionnaires about their well-being before starting the study treatment for their blood cancer, and again a few times while taking the medication, to see if there were any changes. There were two groups of patients. One group took ZAN and the other took IBR. The patients could not choose which medicine they were going to take. Results from both groups of patients were compared. Patients taking ZAN did not feel worse or better about their diarrhea and sickness, but those taking IBR said these symptoms had become worse. Both medicines improved how patients were feeling. However, improvement in tiredness and physical ability was larger in patients taking ZAN than those on IBR, especially for the patients whose cancer was getting better. For patients with a rare blood cancer in this study, those taking ZAN had a better quality of life than those taking IBR. In a head-to-head comparison in the Phase III ASPEN study, patients with Waldenström macroglobulinemia treated with zanubrutinib had better quality of life than patients treated with ibrutinib. Waldenström macroglobulinemia (WM) is a rare B-cell lymphoma marked by an excess of monoclonal immunoglobulin-M. Patients with WM experience symptoms including fatigue, muscle weakness, neuropathy and anemia, significantly affecting their health-related quality of life (HRQoL). Bruton tyrosine kinase (BTK) inhibitors, particularly ibrutinib, have shown efficacy in treating WM; however, they are associated with adverse events that can lead to early treatment discontinuation, negatively affecting HRQoL. Zanubrutinib, a next-generation BTK inhibitor, was designed with improved selectivity for BTK to minimize off-target effects and toxicities and thereby potentially improve HRQoL. ASPEN is a randomized, open-label, Phase III study comparing zanubrutinib and ibrutinib in patients with relapsed/refractory or treatment-naive WM. In this study, HRQoL was measured with two validated patient-reported instruments: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 and the EQ-5D-5L. Clinically meaningful improvements in diarrhea and nausea/vomiting symptoms were observed in patients receiving zanubrutinib compared with ibrutinib. Patients with a very good partial response to zanubrutinib had significantly increased HRQoL, particularly in physical functioning and fatigue symptoms. Both treatment arms had consistently improved EQ-5D-5L scores through Cycle 13. This is the first head-to-head study comparing HRQoL in patients with WM treated with different BTK inhibitors. The results reported here are consistent with the primary results of the ASPEN study reported by Tam et al. [10]. In addition to the better efficacy observed with zanubrutinib vs. ibrutinib, zanubrutinib provides a higher quality of life to patients with WM.