Heyman Benjamin M, Opat Stephen S, Wahlin Björn E, Dimopoulos Meletios-Athanasios C, Castillo Jorge J, Tedeschi Alessandra, Tam Constantine S, Buske Christian, Owen Roger G, Leblond Véronique, Trotman Judith, Barnes Gisoo, Chan Wai Y, Schneider Jingjing, Allewelt Heather, Cohen Aileen, Matous Jeffrey V
Hematology, University of California San Diego, San Diego, CA.
Department of Haematology, Lymphoma Research Group, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
Blood Adv. 2025 Feb 25;9(4):722-728. doi: 10.1182/bloodadvances.2024014115.
Peripheral neuropathy (PN) is a significant cause of morbidity associated with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of zanubrutinib with ibrutinib in patients with WM. This ad hoc analysis examined treatment outcomes with zanubrutinib or ibrutinib on PN symptoms associated with WM in patients enrolled in ASPEN. Logistic regression was performed between PN symptom resolution and several predictors. Health-related quality of life (HRQOL) was assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Forty-nine patients with PN symptoms were included (zanubrutinib treated, n = 27; ibrutinib treated, n = 22). Overall, 35 patients (71.4%) experienced resolution of PN symptoms, with a median time to resolution of 10.1 months (range, 1-46.8). In cohort 1 (MYD88 mutation), the median time to PN symptom resolution was 4.6 months (range, 1.1-46.8) with zanubrutinib and 14.1 months (range, 1-44) with ibrutinib. Logistic regression demonstrated a significant relationship between PN symptom resolution and both major response and lower baseline anti-myelin-associated glycoprotein antibody levels. Patients with PN symptom resolution had greater improvement in HRQOL. Physical functioning improved in patients with PN symptom resolution and was unchanged in patients without resolution. Improvements observed in PN symptoms may be in response to a reduction in immunoglobulin M. Although further investigation is required, this analysis supports the potential use and further exploration of Bruton tyrosine kinase inhibitors to treat PN symptoms in patients with WM. This trial was registered at www.clinicaltrials.gov as #NCT03053440.
周围神经病变（PN）是与华氏巨球蛋白血症（WM）相关的发病的重要原因。3期ASPEN研究比较了泽布替尼与伊布替尼在WM患者中的疗效和安全性。这项专项分析研究了在ASPEN研究中入组的WM患者使用泽布替尼或伊布替尼治疗PN症状的结果。对PN症状缓解与多个预测因素进行了逻辑回归分析。使用经过验证的欧洲癌症研究与治疗组织生活质量问卷核心30来评估健康相关生活质量（HRQOL）。纳入了49例有PN症状的患者（接受泽布替尼治疗，n = 27；接受伊布替尼治疗，n = 22）。总体而言，35例患者（71.4%）的PN症状得到缓解，缓解的中位时间为10.1个月（范围为1 - 46.8个月）。在队列1（MYD88突变）中，使用泽布替尼时PN症状缓解的中位时间为4.6个月（范围为1.1 - 46.8个月），使用伊布替尼时为14.1个月（范围为1 - 44个月）。逻辑回归表明PN症状缓解与主要反应和较低的基线抗髓鞘相关糖蛋白抗体水平均存在显著关系。PN症状缓解的患者HRQOL改善更大。PN症状缓解的患者身体功能有所改善，未缓解的患者身体功能无变化。PN症状的改善可能是由于免疫球蛋白M减少所致。尽管需要进一步研究，但该分析支持在WM患者中使用布鲁顿酪氨酸激酶抑制剂治疗PN症状的潜在用途和进一步探索。该试验在www.clinicaltrials.gov上注册，编号为#NCT03053440。
