Peripheral Neuropathy from Immunotherapy: Prevention and Management

Peripheral neuropathy—nerve damage causing numbness, tingling, and pain—can occur with certain targeted therapies like ADCETRIS and combination regimens. Understanding early symptoms and management strategies helps maintain quality of life and treatment efficacy.

**Understanding Treatment-Related Neuropathy**

What Is Peripheral Neuropathy?
- Damage to peripheral nerves (outside brain and spinal cord)
- Affects sensation, movement, or autonomic function
- Can be temporary or permanent
- Severity ranges from mild tingling to disabling weakness

Common Causes in Cancer Treatment:
- ADCETRIS (brentuximab vedotin) - 55% incidence
- Chemotherapy agents (taxanes, platinum drugs, vinca alkaloids)
- Some targeted therapies
- Combination treatments increase risk

**Types of Neuropathy**

Sensory Neuropathy (Most Common):
- Numbness and tingling ("pins and needles")
- Reduced ability to feel pain, temperature, touch
- Usually starts in toes/fingers, spreads upward
- "Stocking-glove" distribution

Motor Neuropathy:
- Muscle weakness
- Difficulty walking, climbing stairs
- Trouble with fine motor tasks (buttoning, writing)
- Foot drop in severe cases

Autonomic Neuropathy (Rare):
- Blood pressure changes
- Heart rate irregularities
- Digestive problems
- Bladder dysfunction

**Recognizing Symptoms**

Early Warning Signs:
- Tingling in fingertips or toes
- Mild numbness in hands or feet
- Difficulty feeling texture or temperature
- Clumsiness with small objects
- Sensitivity to cold

Progressive Symptoms:
- Burning or shooting pain
- Increased numbness spreading up arms/legs
- Difficulty walking, especially in dark
- Balance problems, frequent stumbling
- Muscle cramps or weakness
- Dropping objects frequently

Severe Symptoms:
- Inability to feel feet when walking
- Significant weakness limiting mobility
- Disabling pain
- Falls due to balance loss
- Inability to perform daily tasks

**Severity Grading**

Grade 1 (Mild):
- Mild symptoms
- No interference with function
- Sensory changes only

Grade 2 (Moderate):
- Moderate symptoms
- Interfering with instrumental activities (cooking, shopping)
- May affect fine motor skills

Grade 3 (Severe):
- Severe symptoms
- Interfering with self-care activities (dressing, eating)
- Assistive devices may be needed

Grade 4 (Life-Threatening):
- Disabling neuropathy
- Unable to perform basic self-care
- Wheelchair or bed-bound

**Prevention Strategies**

Before Starting Treatment:

Baseline Assessment:
- Neurological exam
- Document pre-existing neuropathy
- Assess risk factors:
* Diabetes
* Prior chemotherapy
* Vitamin deficiencies
* Alcohol use
* Hereditary neuropathy

Optimize Health:
- Control blood sugar if diabetic
- Correct vitamin deficiencies (B12, folate, B6)
- Limit alcohol consumption
- Review medications that may worsen neuropathy

During Treatment:

Neuropathy Monitoring:
- Ask about symptoms before each treatment
- Sensory testing at each visit
- Vibration sense, touch, pin-prick testing
- Strength assessment
- Balance and gait evaluation

Early Detection:
- Report symptoms immediately
- Don't minimize or ignore tingling
- Keep symptom diary
- Document progression

**Treatment Approaches**

Modifying Cancer Treatment:

Dose Reduction:
- Reduce dose of causative agent by 25-50%
- May preserve treatment benefit while limiting toxicity
- Especially important with ADCETRIS

Treatment Delay:
- Hold therapy until symptoms improve
- Usually 1-2 cycles
- Resume at lower dose or reduced frequency

Discontinuation:
- Permanent stop if Grade 3-4 neuropathy
- Severe symptoms unlikely to fully resolve
- Quality of life priority
- Consider alternative treatments

Symptom Management:

For Neuropathic Pain:

First-Line Medications:
- Duloxetine (Cymbalta) 30-60 mg daily
* Best evidence for chemotherapy-induced neuropathy
* Dual benefit: pain + mood
* Start 30 mg × 1 week, then 60 mg

- Gabapentin 300-3600 mg daily
* Start 300 mg bedtime
* Gradually increase every 3-7 days
* Typical effective dose: 1800-3600 mg/day divided TID

- Pregabalin (Lyrica) 150-600 mg daily
* Start 75 mg twice daily
* Increase based on response
* Less frequent dosing than gabapentin

Second-Line Options:
- Tricyclic antidepressants:
* Nortriptyline 25-100 mg bedtime
* Amitriptyline 10-75 mg bedtime
* Side effects limit use (sedation, dry mouth)

- Topical treatments:
* Lidocaine patches 5%
* Capsaicin cream 0.075%
* Compounded topical gels

- Tramadol for severe pain
- Opioids (last resort for severe, refractory pain)

For Numbness and Tingling:
- Often difficult to treat
- Medications less effective than for pain
- Focus on safety and adaptation

For Muscle Cramps:
- Magnesium supplements
- Quinine water (tonic water)
- Gentle stretching
- Muscle relaxants if severe

**Non-Pharmacological Management**

Physical Therapy:
- Gait training and balance exercises
- Strengthening exercises for weak muscles
- Range of motion exercises
- Assistive device training if needed

Occupational Therapy:
- Adaptive equipment for daily tasks
- Fine motor skill exercises
- Energy conservation techniques
- Home safety assessment

Complementary Approaches:
- Acupuncture (modest evidence)
- Massage therapy
- Transcutaneous electrical nerve stimulation (TENS)
- Mind-body techniques for pain management

**Safety Considerations**

Fall Prevention:
- Remove tripping hazards (rugs, clutter)
- Install grab bars in bathroom
- Improve lighting, especially stairs and hallways
- Wear sturdy, non-slip shoes
- Consider walker or cane if balance impaired
- Avoid walking in dark

Hand Safety:
- Use oven mitts for hot items
- Test bath water with elbow before entering
- Be careful with sharp objects
- Inspect feet daily for injuries
- Avoid walking barefoot

Driving:
- Assess ability to feel pedals
- Test reaction time
- Consider occupational therapy driving evaluation
- May need to stop driving if significant foot neuropathy

**Managing Daily Life**

Footwear:
- Properly fitted shoes with good arch support
- Avoid tight shoes that reduce circulation
- Seamless socks to prevent rubbing
- Inspect feet daily for sores or injuries

Temperature:
- Protect hands and feet from extreme cold
- Wear gloves and warm socks in cold weather
- Use caution with heating pads (may not feel burns)

Sleep:
- Loose, breathable bedding
- Foam mattress topper for comfort
- Elevate feet slightly if helps symptoms
- Medications at bedtime for pain control

**Recovery and Long-Term Outlook**

Timeline:
- Symptoms often peak 3-6 months after stopping treatment
- Gradual improvement may occur over 6-12 months
- Some improvement continues up to 2 years
- Complete resolution uncommon if moderate-severe

Factors Affecting Recovery:
- Severity of neuropathy
- Cumulative dose received
- Individual susceptibility
- Early intervention
- Age (older patients recover slower)

Realistic Expectations:
- Mild neuropathy: 80% improve significantly
- Moderate neuropathy: 50-60% improve
- Severe neuropathy: Unlikely to fully resolve
- May have permanent residual symptoms

**Questions to Ask Your Doctor**

- What's my risk of developing neuropathy with my treatment?
- What symptoms should I watch for?
- Should I take any preventive measures?
- At what point would you reduce the dose or stop treatment?
- What medications can help my symptoms?
- Should I see a neurologist?
- Will this get better after treatment ends?

**Patient Success Story**

"After 8 cycles of ADCETRIS, I developed significant tingling and numbness in my fingers and toes. My oncologist reduced the dose for my remaining 8 cycles, and we started gabapentin for symptom control. The numbness stopped progressing, and I was able to complete my full treatment course. Two years later, I still have mild residual numbness in my toes, but it doesn't limit my activities. I'm grateful we caught it early and adjusted treatment before it became severe."

Our team can connect you with pain management specialists and physical therapists experienced in managing treatment-related neuropathy.