Pezzullo Luca, Piscosquito Giuseppe, Settembre Lorenzo, Avventura Stefano, Serio Bianca, De Biasi Giuseppe, Rizzo Michela, Noioso Ciro Maria, D'Addona Matteo, Landolfi Annamaria, Vinciguerra Claudia, Giudice Valentina, Barone Paolo, Selleri Carmine
Hematology and Transplant Center, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy.
Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy.
Eur J Haematol. 2025 May;114(5):802-811. doi: 10.1111/ejh.14384. Epub 2025 Jan 7.
Brentuximab-vedotin (BV)-induced neurotoxicity (BVIN), a frequent adverse event caused by this monoclonal antibody, is the primary reason for dose modification or drug discontinuation, and is characterized by sensory, motor, and/or autonomic peripheral nerve dysfunctions. Although reversible, BVIN can persist for months or years after treatment and negatively affect quality of life (QoL). Currently, BVIN is managed by dose adjustment or drug interruption, leading to an increased risk of disease relapse. Therefore, early recognition and appropriate management are essential to improve clinical outcomes. In this real-life study, we identified predictive factors for moderate/severe BVIN to reduce the risk of irreversible neuropathy. A total of 22 patients treated with BV were enrolled and BVIN was monitored by electro-neurography and neurological examinations every 2 cycles of therapy, while QoL by clinical questionnaires. We showed that recovery rate from moderate/severe BVIN was low, and sensory nerves were the most affected, negatively impacting QoL. BV dose reduction based on interim PET re-evaluation in patients with hematological response resulted in a significant reduction of BVIN onset with high long-term QoL. Therefore, electrophysiological tests could be useful tools to prevent moderate/severe BVIN onset, and their combination with interim PET imaging could allow dosage adjustments thus simultaneously minimizing risks of disease relapse and BVIN development. However, further studies on larger prospective randomized cohorts are needed to confirm our preliminary results.
本妥昔单抗(BV)诱导的神经毒性(BVIN)是这种单克隆抗体引起的常见不良事件,是剂量调整或停药的主要原因,其特征为感觉、运动和/或自主神经周围神经功能障碍。尽管BVIN是可逆的,但在治疗后可能持续数月或数年,并对生活质量(QoL)产生负面影响。目前,BVIN通过剂量调整或药物中断进行管理,这会增加疾病复发的风险。因此,早期识别和适当管理对于改善临床结果至关重要。在这项真实世界研究中,我们确定了中度/重度BVIN的预测因素,以降低不可逆神经病变的风险。共有22例接受BV治疗的患者入组,每2个治疗周期通过神经电图和神经系统检查监测BVIN,同时通过临床问卷评估QoL。我们发现,中度/重度BVIN的恢复率较低,感觉神经受影响最大,对QoL产生负面影响。对血液学有反应的患者基于中期PET重新评估进行BV剂量减少,可显著降低BVIN的发生,并具有较高的长期QoL。因此,电生理检查可能是预防中度/重度BVIN发生的有用工具,将其与中期PET成像相结合可进行剂量调整,从而同时将疾病复发和BVIN发生的风险降至最低。然而,需要对更大规模的前瞻性随机队列进行进一步研究以证实我们的初步结果。