Rate and characteristics of inflammatory neuropathies associated with brentuximab vedotin therapy

Arthur Matthys; Benjamin Bardel; Fabien Le Bras; Alain Créange; Tarik Nordine; Romain Gounot; Saskia Ingen-Housz-Oro; Muriel Carvalho; Jean-Pascal Lefaucheur; Corinne Haioun; Violaine Planté-Bordeneuve; Thierry Gendre

doi:10.1111/ene.16285

Rate and characteristics of inflammatory neuropathies associated with brentuximab vedotin therapy

Eur J Neurol. 2024 Mar 21:e16285. doi: 10.1111/ene.16285. Online ahead of print.

Authors

Arthur Matthys^{1

2}, Benjamin Bardel^{3

4}, Fabien Le Bras⁵, Alain Créange^{1

4}, Tarik Nordine^{3

4}, Romain Gounot⁵, Saskia Ingen-Housz-Oro⁶, Muriel Carvalho⁷, Jean-Pascal Lefaucheur^{3

4}, Corinne Haioun⁵, Violaine Planté-Bordeneuve^{1

4}, Thierry Gendre^{1

4}

Affiliations

¹ Department of Neurology, AP-HP, Henri Mondor University Hospital, Créteil, France.
² Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University, Paris, France.
³ Unit of Clinical Neurophysiology, AP-HP, Henri Mondor University Hospital, Créteil, France.
⁴ Reference Center for Neuromuscular Diseases Nord/Est/Ile-de-France, Paris, France.
⁵ Lymphoid Malignancies Unit, AP-HP, Henri Mondor University Hospital, Créteil, France.
⁶ Department of Dermatology, Paris-Est Créteil University EpiDermE, AP-HP, Henri Mondor University Hospital, Créteil, France.
⁷ Department of Pharmacy, AP-HP, Henri Mondor University Hospital, Créteil, France.

PMID: 38511878
DOI: 10.1111/ene.16285

Abstract

Background and purpose: Peripheral neuropathy is a frequent complication of brentuximab vedotin (BV), used in CD30+ lymphoma treatment. Classic BV-induced neuropathy (BV-CN) is a mild distal sensory axonal polyneuropathy. Severe BV-induced inflammatory neuropathies (BV-IN) have been described. BV-IN contribute to lymphoma-associated morbidity but might be immunotherapy-responsive. Our primary objective was to evaluate the rate of BV-IN. Our secondary objectives were to determine risk factors and warning signs.

Methods: We conducted a retrospective cohort study on all patients treated with BV at our center between April 2014 and September 2021. Clinical, biological, and electrophysiological data were collected. BV-induced neuropathy was defined as the occurrence of neuropathy up to 3 months after BV discontinuation. BV-IN was defined with criteria adapted from European Academy of Neurology/Peripheral Nerve Society 2021 electrodiagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Other neuropathies were classified as BV-CN.

Results: Among 83 patients, 41 (49%) developed neuropathy: 35 BV-CN and 6 BV-IN. Thus, the rate of BV-IN was 7.2%. Compared to patients with BV-CN, no predisposing factor was identified. However, patients with BV-IN more frequently presented muscle weakness (67% vs. 5.7%, p < 0.05), gait disorders (83% vs. 20%, p < 0.05), or acute or subacute onset (67% vs. 14%, p < 0.05). BV-IN was frequently more severe (Common Terminology Criteria for Adverse Events grade ≥3; 50% vs. 0%, p < 0.05). Four patients were treated with immunotherapy.

Conclusions: Brentuximab vedotin-induced neuropathy is an overlooked complication. Based on four easily identifiable "red flags", we provide an algorithm to help non-neurologist physicians that care for BV-treated patients to detect BV-IN. The aim of the algorithm is to decrease the diagnostic and management delay of this disabling neuropathy.

Keywords: brentuximab vedotin; chemotherapy‐induced peripheral neuropathy; chronic inflammatory demyelinating polyradiculoneuropathy; immune‐related adverse events; inflammatory neuropathy.