Electrophysiological Studies in Combination With Interim-Positron Emission Tomography Scan for Prevention of Severe Brentuximab-Vedotin-Induced Neurotoxicity

Abstract

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.

Keywords: brentuximab‐vedotin; lymphoma; neurotoxicity; prevention; quality of life.

FIGURE 1

Neurological toxicity in the prospective cohort. (A) Signs and symptoms of neurological toxicity evidenced by clinical examination after 2 (T2), 4 (T4), and 6 (T6) months of therapy. (B) Medical Research Council (MRC), Douleur Neuropathique en 4 Questions (DN4), Sensory Symptoms Score (SSyS), and Sensory Sum Score (SSuS) values are reported for each timepoint. (C) Scores for the subjective perception of neurological symptoms. DTR, deep tendon reflexes.

FIGURE 2

Electroneurography in the prospective cohort. Results for (A) motor and (B) sensory nerves after 2 (T2), 4 (T4), and 6 (T6) months of therapy. RMU, right motor ulnar nerve; LMM, left motor ulnar nerve; RMP, right motor peroneal nerve; LMP, left motor peroneal nerve; RMT, right motor tibial nerve; LMT, left motor tibial nerve; RSU, right sensory ulnar nerve; LSM, left sensory medial nerve; RSS, right sensory sural nerve; LSS, left sensory sural nerve; RSP, right sensory superficial peroneal nerve; LSP, left sensory superficial peroneal nerve.

FIGURE 3

Neurological toxicity comparison between prospective and retrospective cohorts. (A) Medical Research Council (MRC), Douleur Neuropathique en 4 Questions (DN4), Sensory Symptoms Score (SSyS), and Sensory Sum Score (SSuS) values are reported for the prospective cohort after 6 months of therapy and for the retrospective group. (B) Scores for the subjective perception of neurological symptoms. *p < 0.05.

FIGURE 4

Electroneurography comparison between prospective and retrospective cohorts. Results for (A) motor and (B) sensory nerves for the prospective cohort after 6 months of therapy and for the retrospective group. RMU, right motor ulnar nerve; LMM, left motor ulnar nerve; RMP, right motor peroneal nerve; LMP, left motor peroneal nerve; RMT, right motor tibial nerve; LMT, left motor tibial nerve; RSU, right sensory ulnar nerve; LSM, left sensory medial nerve; RSS, right sensory sural nerve; LSS, left sensory sural nerve; RSP, right sensory superficial peroneal nerve; LSP, left sensory superficial peroneal nerve. *p < 0.05; **p < 0.01.