Brentuximab-Induced Peripheral Neurotoxicity: A Multidisciplinary Approach to Manage an Emerging Challenge in Hodgkin Lymphoma Therapy

Abstract

Brentuximab vedotin (BV) is an anti-CD30 antibody–drug conjugate approved to treat classical Hodgkin lymphoma (HL). BV-induced peripheral neurotoxicity (BVIN) is one of the greatest concerns for haematologists treating HL for several reasons. First, BVIN is highly frequent. Most patients receiving BV will experience some degree of BVIN, resulting in the primary reason for dose modification or discontinuation of HL therapy. Second, BV produces sensory, motor, and/or autonomic peripheral nerve dysfunction, which can present as severe, disabling forms of BVIN—predominantly motor—in some patients. Third, although largely reversible, BVIN may persist months or years after treatment and thereby become a major issue in HL survivorship. BVIN may, therefore, negatively affect the quality of life and work-life of often young patients with HL, in whom long-term survival is expected. Currently, the only strategy for BVIN includes dose adjustments and treatment discontinuation; however, this could interfere with LH therapy efficacy. In this setting, early recognition and adequate management of BVIN are critical in improving clinical outcomes. Careful neurologic monitoring may allow accurate diagnoses and gradation of ongoing forms of BVIN presentation. This review analysed current, available data on epidemiology, pathophysiology, patient- and treatment-related risk factors, clinical and neurophysiologic phenotypes, and management in patients with HL. Furthermore, this review specifically addresses limitations posed by BVIN assessments in clinical practice and provides skills and tools to improve neurologic assessments in these patients. Integrating this neurotoxic drug in clinical practice requires a multidisciplinary approach to avoid or minimise neurotoxicity burden in survivors of HL.

Anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma with primary bone involvement: a case report

“…Therefore, A+CHP has been used for the first-line treatment of ALK + ALCL in recent years. However, BV-induced peripheral neurotoxicity (BVIN) is a major reason for the limited clinical application of BV ( 15 ). Similar to the symptom of peripheral nerve involvement caused by the use of vincristine, the most common form of BVIN is the symmetrical socking-glove pattern ( 15 , 16 ).…”

Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers

“…Adcetris ® -induced axon degeneration and peripheral neurotoxicity are thought to be caused by off-target effects of the microtubule-binding MMAE payload, and not related to the CD30 target antigen [ 105 ]. Due to the long projections involved, axonal transport between neuronal cell bodies and distal nerve endings is highly microtubule-dependent, making peripheral nerves especially susceptible to MMAE toxicity [ 106 ].…”

Cutaneous Lymphoma and Antibody-Directed Therapies

“…The most common adverse event reported is peripheral neuropathy: nerve damage does not seem to be a CD30-mediated mechanism but rather the effect of MMAE-mediated inhibition of microtubule-dependent axonal transport. Other relatively common adverse events are fatigue, nausea, upper respiratory tract infections, and neutropenia [ 74 , 81 , 82 ]. Despite the overall efficacy and safety profile, resistance to BV is a recognized event and its underlying mechanisms have been characterized.…”