What is the recommended management of neck pain associated with Brentuximab‑AVD (brentuximab vedotin plus doxorubicin, vinblastine, dacarbazine) chemotherapy?

Management of Neck Pain Associated with Brentuximab-AVD Chemotherapy

Neck pain during Brentuximab-AVD (A+AVD) treatment is most commonly a manifestation of peripheral neuropathy, which occurs in approximately 80% of patients, and should be managed with dose modification or discontinuation of brentuximab vedotin while continuing AVD chemotherapy. 1

Understanding the Etiology

• Peripheral neuropathy is the primary toxicity of brentuximab vedotin in the A+AVD regimen, affecting 80% of patients in real-world practice, with 10% experiencing grade 3 severity 1
• Neck pain specifically represents cervical nerve involvement as part of the broader peripheral neuropathy syndrome caused by the microtubule-disrupting effects of brentuximab vedotin 1, 2
• This differs from vinblastine-related neuropathy, which is typically less severe when used without brentuximab 2

Immediate Assessment and Grading

Evaluate the severity using CTCAE grading:

• Grade 1: Asymptomatic or mild symptoms; clinical findings only → Continue treatment with close monitoring 1
• Grade 2: Moderate symptoms limiting instrumental activities of daily living → Reduce brentuximab dose or hold temporarily 1
• Grade 3: Severe symptoms limiting self-care activities → Discontinue brentuximab vedotin immediately 1

Treatment Modification Algorithm

For Grade 2 peripheral neuropathy (including neck pain):

• Reduce brentuximab vedotin dose from 1.8 mg/kg to 1.2 mg/kg while continuing full-dose AVD 1
• If symptoms persist or worsen, discontinue brentuximab and complete remaining cycles with AVD alone 1

For Grade 3 peripheral neuropathy:

• Discontinue brentuximab vedotin permanently and complete treatment with AVD alone 1, 2
• This approach maintains efficacy, as patients who discontinued brentuximab due to neuropathy did not have inferior progression-free survival 1

Symptomatic Management

• Initiate gabapentin 300 mg orally three times daily, titrating up to 900 mg three times daily as needed for neuropathic pain relief (general medical knowledge)
• Alternative: duloxetine 30-60 mg daily for neuropathic pain management (general medical knowledge)
• Physical therapy consultation for neck range-of-motion exercises and pain management strategies (general medical knowledge)

Critical Safety Considerations

• Do NOT continue full-dose brentuximab in the presence of grade 2-3 neuropathy, as this can lead to permanent nerve damage 1
• In real-world practice, 44% of patients required brentuximab modification due to peripheral neuropathy, with 23% requiring complete discontinuation 1
• Most patients (69%) experience resolution or improvement of neuropathy after brentuximab discontinuation, though this may take months 1, 2

Prognosis and Reassurance

• Discontinuing brentuximab due to neuropathy does not compromise cancer outcomes, with 2-year progression-free survival of 82.7% maintained even in patients who stopped brentuximab early 1
• The 6-year overall survival with A+AVD is 93.9%, significantly superior to ABVD (89.4%), even accounting for neuropathy-related modifications 2
• Resolution or amelioration of peripheral neuropathy occurred in most patients by final follow-up, though complete resolution was documented in only 36% 1, 2

Common Pitfalls to Avoid

• Do not attribute neck pain to musculoskeletal causes without first considering drug-induced peripheral neuropathy in patients receiving A+AVD 1
• Do not delay dose modification hoping symptoms will spontaneously resolve, as continued exposure worsens neuropathy severity 1
• Do not use granulocyte colony-stimulating factor prophylaxis to maintain brentuximab dosing through neuropathy, as G-CSF does not prevent or treat peripheral neuropathy 2