P013 | PREVENTING BRENTUXIMAB-VEDOTIN NEUROTOXICITY IN HODGKIN LYMPHOMA VIA ELECTROPHYSIOLOGY AND INTERIM PET

Introduction Brentuximab vedotin (BV) is an effective anti-CD30 antibody–drug conjugate for Hodgkin lymphoma (HL), yet its use is frequently limited by BV-induced neurotoxicity (BVIN), characterized by sensory, motor, and/or autonomic nerve dysfunctions. Although reversible in most cases, BVIN may persist and negatively affect quality of life (QoL). As dose reduction or discontinuation may increase relapse risk, early identification is crucial. This study aims to identify early predictors of moderate/severe BVIN through neurological monitoring and interim PET (iPET), enabling timely dose modulation. Methods We enrolled 22 patients (18 HL, 4 NHL) in a monocentric prospective and retrospective study. Neurological assessments and electroneurography (ENG) were performed every 2 cycles (prospective) or post-therapy (retrospective). BVIN was graded via clinical scales (MRC, DN4, SSyS, SSuS) and patient questionnaires. iPET (Deauville Score) guided BV dose reduction in responders. Neurological evaluations were scheduled at T0 (baseline), T2 (2 months, median cumulative BV dose 400 mg), T4 (4 months), and T6 (6 months). Results At T2 (400 mg cumulative BV), 50% of prospective patients reported reduced tactile sensitivity, 40% paresthesia, and 30% neuropathic pain or reduced deep tendon reflexes (DTR). These increased by T6 to 87.5% for tactile and DTR deficits, 62.5% for vibratory loss, and 37.5% for pain. Grade I toxicity remained stable (12.5%). Subjective symptom scores worsened from median 11.5/60 at T2 to 19/60 at T4. ENG showed early sensory action potential (SAP) and compound muscle action potential (CMAP) reductions, especially in sural, superficial peroneal, and tibial nerves. SAP dropped >50% in 63% of patients at T6. Compared to the retrospective cohort (50% with grade I toxicity), prospective monitoring reduced severe BVIN (p=0.1577) and improved perception scores. Patients who underwent PET-guided BV dose reduction showed significantly better neurological outcomes than those maintaining full dosage (p = 0.0418). PET-guided dose reduction significantly correlated with better QoL (p=0.0418), with no impact on disease control. Conclusion Combined ENG and interim-PET allow early detection and prevention of BVIN, improving tolerability without compromising efficacy. Monitoring sural and tibial nerves and using patient-reported outcomes are effective for tailoring BV therapy in HL.