Global expert panel issues first consensus roadmap for brentuximab vedotin nerve damage

Brentuximab vedotin has transformed the outlook for patients with CD30-positive lymphomas, but the antibody-drug conjugate carries a neurological price that clinicians have long managed without a unified playbook. Peripheral neuropathy strikes up to two-thirds of patients treated with the drug, forcing dose cuts, treatment delays and, in some cases, permanent discontinuation of a therapy that may be the best option available. Now, an international panel of 13 experts from eight countries has produced the most comprehensive consensus to date on how to assess, monitor and manage this treatment-induced nerve damage, publishing its recommendations in Supportive Care in Cancer.

The drug itself is a molecular hybrid engineered for precision. A monoclonal antibody directed against CD30, a protein abundantly displayed on malignant cells in classical Hodgkin lymphoma, systemic anaplastic large cell lymphoma, peripheral T-cell lymphoma and cutaneous T-cell lymphoma, is chemically linked to monomethyl auristatin E, an agent that disrupts microtubules and halts cell division. Selective delivery limits collateral damage to healthy tissue, yet the microtubule poison still finds its way into peripheral nerves, where it accumulates with cumulative dose and treatment duration. Extended single-agent courses, such as those used for cutaneous T-cell lymphoma, produce more severe and longer-lasting neuropathy than shorter combination regimens.

Clinically, the damage follows a characteristic pattern. Patients typically develop tingling, numbness and burning sensations in a distal, symmetrical distribution affecting the hands and feet. Less frequently, motor involvement produces cramps and distal weakness, while autonomic features such as orthostatic hypotension or gastrointestinal dysmotility can appear. Although the neuropathy is often reversible, complete resolution may take months to years, and some patients experience persistent symptoms that erode quality of life. The economic toll is substantial too, with increased hospitalisation rates, emergency department visits and outpatient encounters documented across healthcare systems.

To build the consensus, the researchers turned to a modified Delphi methodology, a structured process designed for areas where robust empirical evidence is scarce. A three-member steering committee, comprising a neurologist, a haematology oncologist and a dermatology oncologist from Spain, Australia and Brazil, reviewed the protocol and led statement development without participating in voting. Fifteen experts agreed to join the panel, recruited to represent neurology, haematology-oncology, dermatology-oncology, nursing and rehabilitation, and 13 completed all three survey rounds conducted between July and November 2025. Statements were drafted from a targeted literature review of publications from 2014 to 2024 and refined across rounds, with consensus defined as at least 70 percent agreement or disagreement on six-point Likert scales.

The panel achieved consensus on 60 of 87 statements, or 69 percent, spanning risk factor assessment, symptom monitoring, pharmaceutical management and non-pharmaceutical strategies. Among the strongest agreements, 92 percent of panellists endorsed routine risk factor profiling before initiating brentuximab vedotin, including assessment of personal and family history of hereditary neuropathies. High cumulative drug dose, prior or concurrent neurotoxic therapy such as vincristine or vinblastine, and comorbidities like diabetes were identified as key risk factors, each reaching agreement rates of 77 to 85 percent. Early warning signs demanding immediate intervention included distal weakness, loss of balance resulting in falls, and rapid progression of sensation loss.

On diagnosis, the panel unanimously agreed that healthcare professionals should ask patients about neuropathy symptoms at every visit, while remaining alert to underreporting, particularly among patients with poorer prognoses who may fear losing access to the drug. Validated assessment tools should be applied at baseline and at least every three treatment cycles, with the Total Neuropathy Score clinical version, or TNSc, recognised as an effective diagnostic and grading instrument by 92 percent of panellists. The Common Terminology Criteria for Adverse Events, or CTCAE, failed to reach consensus as a standalone tool, though panellists supported using it alongside the TNSc and patient-reported outcomes. Nerve conduction studies are not routine for typical presentations but should be considered in severe neuropathy, diagnostic uncertainty, atypical courses, or suspected Guillain-Barré Syndrome, where intravenous immunoglobulin or plasma exchange is supported in confirmed cases.

Dose modification recommendations revealed both clarity and persistent uncertainty. For Grade 1 neuropathy, no dose changes are required. For Grade 2 neuropathy on the BV plus CHP regimen, reduction from 1.8 to 1.2 milligrams per kilogram, up to a maximum of 120 milligrams every three weeks, was supported. In a notable departure from the prescribing label, the panel agreed that when brentuximab vedotin is combined with doxorubicin, vinblastine and dacarbazine, vinblastine dose reduction may be considered before adjusting the antibody-drug conjugate itself. For Grade 3 neuropathy on BV plus AVD in Hodgkin lymphoma, withholding the drug until improvement to Grade 2 or lower, then resuming at 0.9 milligrams per kilogram, reached consensus. Grade 4 neuropathy warrants permanent discontinuation. Dose reduction was judged more effective at mitigating neuropathy than prolonging the interval between doses, and patients with pre-existing Grade 3 or higher neuropathy should be excluded from receiving the drug.

Intermediate-grade neuropathy remains the murkiest territory. Grade 3 and above neuropathy affects roughly six percent of patients with classical Hodgkin lymphoma, meaning direct clinical experience is limited and robust data on symptom resolution rates are lacking. Patients at greatest risk, such as those with high cumulative neurotoxic exposure in the relapsed or refractory setting, typically have poorer prognoses and fewer alternatives. Free-text responses indicated that management decisions are context-dependent, with physicians more likely to modify dosing when Grade 2 neuropathy appears early in treatment rather than near the end. The newly approved BrECADD combination regimen was not explored, as it received approval after the Delphi protocol was finalised.

Beyond pharmacology, the panel endorsed a multidisciplinary support framework. Physical therapy was identified as an effective non-pharmaceutical option by 77 percent of panellists, and all agreed that physiotherapists and occupational therapists can improve physical quality of life through interventions such as sensory re-education and graded tactile tasks. Psychologists and counsellors play a key role in supporting emotional wellbeing, while social workers may assist when severe neuropathy leads to dependence in daily living. Analgesics including duloxetine, pregabalin and gabapentin may be considered for neuropathic pain, though the panel recognised variability in their effectiveness and lacked consensus on whether pain medications risk masking symptoms during monitoring. Patients receiving the drug should avoid excessive pyridoxine intake, given its potential to exacerbate nerve damage.

Shared decision-making emerged as a unifying principle across all recommendations. The panel unanimously agreed that patient choice is central to dose modification decisions and that clinicians should consider lifestyle and occupation when discussing impact, noting that musicians, surgeons and artists reliant on fine motor skills may experience disproportionate consequences even at lower neuropathy grades. The panel called for clearer evidence-based guidelines on diagnosis, pharmaceutical and non-pharmaceutical management, and additional research to identify predictive factors for severe or irreversible neuropathy. Pharmacists were not represented on the panel, and participants from the United States and Canada were excluded because separate consensus activities were underway in those regions, meaning the recommendations should not be interpreted as a global consensus. Nevertheless, the framework lays the groundwork for future guideline development, with the ultimate goal of preserving both lymphoma control and neurological function.

Subject of Research: Expert consensus on managing brentuximab vedotin-induced peripheral neuropathy in lymphoma

Article Title: Expert consensus on the management of peripheral neuropathy in patients with lymphoma on brentuximab vedotin

Article References: Velasco, R., Sanches, J. A., Argyriou, A. A., Cavaletti, G., Domingo-Domenech, E., Fosså, A., Gállego Pérez-Larraya, J., Ruiz, A. M., Molassiotis, A., Neder Ramires Abdo, A., Ortiz-Romero, P. L., Park, S. B., Scarisbrick, J., Urwin, L., Wang, M., & Prince, H. M. (2026). Expert consensus on the management of peripheral neuropathy in patients with lymphoma on brentuximab vedotin. Supportive Care in Cancer, 34(11), Article 1116. https://doi.org/10.1007/s00520-026-11314-5

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11314-5

Keywords: brentuximab vedotin, peripheral neuropathy, lymphoma, Delphi consensus, antibody-drug conjugate, dose modification, neurotoxicity, supportive care, Hodgkin lymphoma, patient-reported outcomes, multidisciplinary care, chemotherapy-induced neuropathy