Muscle Weakness in Melanoma Treatment: What to Expect

Muscle weakness can occur during melanoma treatment, but how common it is depends on the therapy you receive. Immunotherapy (like ipilimumab and nivolumab) can trigger inflammation in muscles (myositis) or affect nerves, leading to weakness in some people. ^[1] Immune‑related muscle and joint problems may include stiffness, weakness, pain, and swelling; these can range from mild to severe. ^[1] Chemotherapy used for melanoma (for example, dacarbazine) often causes general fatigue and weakness, which many people describe as feeling “wiped out.” ^[2] Taxane- or platinum‑based regimens sometimes used alongside immunotherapy can cause peripheral neuropathy (nerve damage), which may include sensory changes and, less commonly, motor weakness. ^{[3] [4]}

Why Muscle Weakness Happens

• Immunotherapy‑related inflammation: Checkpoint inhibitors can cause immune‑related adverse events affecting muscles (myositis) and nerves (neuropathy), and even neuromuscular junction problems like myasthenia gravis in rare cases. ^[5] These effects are usually infrequent but can be serious if they escalate. ^[6]
• Chemotherapy effects: Some chemotherapy agents for melanoma are associated with systemic weakness and fatigue due to their impact on rapidly dividing cells and overall energy levels. ^[2]
• Peripheral neuropathy from certain drugs: Agents such as paclitaxel or platinum compounds can injure peripheral nerves, leading to numbness, tingling, burning pain, and sometimes muscle weakness or myopathy; symptoms can be sudden or progressive. ^[3] These neuropathies may improve after stopping treatment, though severe cases can persist longer. ^{[7] [4]}

In short, muscle weakness is not universal, but it is a recognized side effect across several melanoma treatment types, with different mechanisms and severities. ^{[1] [2] [3]}

When to Seek Immediate Help

• Rapidly worsening weakness, trouble swallowing or breathing, or severe neck stiffness can signal serious immune‑related toxicity and needs urgent evaluation. ^[8]
• New dark urine, yellowing of eyes/skin, unexplained bruising, or severe abdominal pain may indicate other immune‑related organ issues that require prompt assessment. ^[1]
• New neurological symptoms such as double vision, severe headache, or weakness that limits daily activities should be reported right away because immune‑related adverse events can escalate quickly. ^[6]

How Muscle Weakness Is Evaluated

• Clinical assessment and grading of severity: Your care team will assess how much weakness affects daily activities and may temporarily hold immunotherapy if symptoms are moderate to severe. ^[9]
• Blood tests for muscle inflammation: Typical work‑up for suspected myositis includes CK (creatine kinase), aldolase, ESR and CRP, and sometimes autoantibody panels. ^[10]
• Neurologic evaluation: Depending on symptoms, doctors may order nerve conduction studies, EMG, thyroid panel, cortisol/ACTH, or paraneoplastic and autoimmune testing to clarify the cause. ^{[10] [9]}

Early testing helps distinguish muscle inflammation from nerve injury and guides safe adjustments to treatment. ^{[10] [9]}

Management Strategies

Immunotherapy‑Related Weakness (Myositis/Neuropathy)

• Hold or pause the checkpoint inhibitor until symptoms stabilize for moderate or worse weakness. ^[9]
• Start corticosteroids (for example, prednisone) if immune‑related muscle or nerve inflammation is suspected; dosing and taper depend on severity and response. ^[6]
• Escalation for severe cases: If symptoms are severe or not improving, clinicians may add IVIG, plasmapheresis, or steroid‑sparing immunosuppressants based on specialist guidance. ^[6]
• Monitoring plan: Repeat CK/aldolase and inflammatory markers, track functional status, and adjust therapy accordingly. ^[10]

Chemotherapy‑Associated Weakness and Fatigue

• Energy conservation and pacing: Plan activities for times of higher energy, take frequent breaks, and prioritize essential tasks. General fatigue and weakness are common with agents like dacarbazine. ^[2]
• Physical therapy and gentle exercise: Structured, low‑impact strengthening and balance work can improve stamina and reduce deconditioning; progress gradually based on tolerance.
• Nutrition and hydration: Aim for adequate protein and fluids to support muscle recovery; consider small, frequent meals if appetite is low.
• Symptom control: Treat pain, sleep problems, and mood changes, which can worsen perceived weakness.

Neuropathy‑Related Weakness

• Dose adjustments or scheduling changes: For taxanes or platinum compounds, clinicians may reduce dose or change schedules to limit nerve toxicity. ^[4]
• Medications for neuropathic symptoms: Agents like duloxetine, gabapentin/pregabalin, or topical therapies can help pain and paresthesias, which may indirectly improve function. ^[3]
• Safety and fall prevention: Use supportive footwear, assistive devices if needed, and home safety measures to reduce fall risk while nerves recover. ^[3]
• Recovery expectations: Many neuropathies improve over weeks to months after treatment ends, though some symptoms can persist; track changes and report progression. ^{[7] [4]}

Practical Self‑Care Tips

• Listen to early warning signs: New stiffness, cramping, or unusual fatigue that doesn’t match your usual pattern merits a quick check‑in with your team. ^[1]
• Keep a symptom diary: Note onset, triggers, severity, and impact on daily tasks to guide clinical decisions.
• Coordinate medications: Before starting any new drug or supplement, clear it with your oncology team to avoid interactions that could worsen side effects. ^[8]
• Use pain strategies wisely: Non‑steroidal anti‑inflammatories or acetaminophen can help arthralgia/myalgia if appropriate; dosing should be tailored and monitored for safety. ^[11]

What Your Care Team May Change

• Temporarily hold immunotherapy during evaluation of moderate or severe weakness and resume only when stable, following graded toxicity guidance. ^[9]
• Switch or adjust regimens if neuropathy emerges on taxane/platinum combinations to prevent progression. ^[4]
• Add specialist input (neurology, rheumatology, rehabilitation) for complex muscle or nerve involvement and to optimize recovery. ^[6]

Bottom Line

Muscle weakness can happen with melanoma treatments most often as general fatigue/weakness with chemotherapy, and less commonly as immune‑related myositis or neuropathy with immunotherapy. ^{[2] [1]} With early recognition, appropriate testing, and tailored management (including steroid treatment when immune‑related inflammation is suspected), most people can safely continue therapy or recover function. ^{[10] [6]} Clear communication with your team and practical self‑care strategies make a meaningful difference. ^{[8] [11]}