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Multifocal Tendon Ruptures During Nivolumab and Ipilimumab Therapy for Metastatic Melanoma: A Case Report.

In recent years, immunotherapy has emergedas apowerful treatment option for many patients, either alone or in combination with chemotherapy. Patients with melanoma are among a limited patient population who receive combined immunotherapy. These patients are at increased risk of immunotherapy toxicity in multiple organ systems such as hepatitis, myositis, polymyalgia rheumatica, myalgias, and arthralgias. When such toxicities arise, high-dose corticosteroids are often utilized to prevent worsening of severe immunotherapy-related toxicity. However, extended use of high-dose corticosteroids can also place those patients being treated for immunotherapy-related toxicities at risk for toxic tendinopathies.We report a novel case of multifocal tendon rupture of the bilateral biceps, Achilles, and extensor digitorum tendons of all fingers following immunotherapy and concomitant, prolonged high-dose corticosteroids, which resulted in profound functional impairment and required inpatient rehabilitation. The patient provided informed consent for this report. Institutional review board approval is waived for deidentified case reports of fewer than three patients at our institution. A 58-year-old white man diagnosed with metastatic melanoma was initiated on standard nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) following appropriate surgical management. One week after the third cycle of immunotherapy, he developed severe immune-mediated hepatitis andwas initiated on high-dose corticosteroids (prednisone 80 mg daily and one dose of intravenous methylprednisolone 60 mg). Due to persistently rising increasing levels on liver function tests (ultimately peaking with aspartate aminotransferase [AST] >600 U/L, alanine aminotransferase [ALT] >2200 U/L, and total bilirubin 2.3 mg/dL), steroids were serially increased after 1 week to prednisone 120 mg daily withmycophenolate 1000 mg daily for 5 days and then to prednisone 150 mg daily with mycophenolate 1500 mg daily. The patient was briefly hospitalized to administer intravenous steroids (1-2 mg/kg/day) and liver biopsy showed pathology consistent with immunemediated hepatitis due to immune checkpoint inhibitor treatment. He was discharged home on prednisone 150 mg daily and mycophenolate 3000 mg daily. One month after his third cycle of immunotherapy, he started reporting bilateral shoulder pain, bilateral knee pain, and left Achilles pain, all worse with movement. This was attributed to arthralgias from mycophenolate, so the dose was reduced to 1500 mg daily. Two weeks after his initial pains, he could no longer walk and had significant functional limitations, requiring a scooter for mobility and moderate to maximal assistance with transfers and activities of daily living from his family. He was referred to physical therapy but continued to deteriorate, additionally noting anorexia and 30-pound weight loss since the beginning immunotherapy. Over the following 2 weeks he also developed poor hand function with bruising over the dorsum of both hands. Two months after last immunotherapy, his liver function test values finally decreased to three times the upper limit of normal, and doses of prednisone and mycophenolate were adjusted to 120 and 2000 mg daily, respectively. He then presented to our cancer center to further investigate the etiology of functional decline. Extensive rheumatologic and neurologic assessments with electromyography and muscle biopsy revealed generalized myopathy with predominantly motor polyneuropathy and inflammatory myositis, respectively. Following continued steroids and plasmapheresis, he was transferred to acute inpatient rehabilitation where he was first noted to have tendon ruptures of the bilateral long head of the biceps, Achilles, and extensor digitorum tendons of all fingers on both hands, confirmed by examination and imaging (Figure 1). See Figure 2 for summary of events timeline. Of note, all digits could be easily passively ranged to full extension at time of admission. He also had ongoing bilateral knee pain upon discharge from inpatient rehab, suggesting high risk for bilateral quadriceps/patellar tendon ruptures. High-dose corticosteroid use alone is associated with increased risk of tendon rupture, most commonly the Achilles and patellar tendons, less commonly the biceps tendons, and rarely the extensor tendons of the wrist and hand. However, case reports by Blanco et al describe isolated tendon ruptures typically in only one of these locations associated with corticosteroids, PM R 14 (2022) 151–153 www.pmrjournal.org