A Case Report of Drug-Induced Myopathy Involving Extraocular Muscles after Combination Therapy with Tremelimumab and Durvalumab for Non-Small Cell Lung Cancer

Abstract

Recently developed anti-tumour therapies targeting immune checkpoints include tremelimumab and durvalumab. These agents have incompletely characterised side effect profiles. The authors report a 68-year-old man treated for non-small cell lung cancer (NSCLC) with a combination of tremelimumab and durvalumab. After treatment he developed diplopia, ptosis, fatigue, weakness, and an inflammatory myopathy affecting the extraocular muscles requiring hospitalisation. Electromyography (EMG) testing and muscle biopsy suggested inflammatory myopathy without sign of myasthenia. Within 1 month of withdrawal of cancer therapies and initiation of oral steroid therapy, ocular and systemic symptoms had resolved. This notable adverse effect has not been previously described for these drugs administered singly or in combination, and ophthalmologists should be aware of this presentation in patients treated with these agents.

Clinical features, predictive correlates, and pathophysiology of immune-related adverse events in immune checkpoint inhibitor treatments in cancer: a short review

“…Atezolizumab, durvalumab, and avelumab are the newest ICIs to be approved by the FDA, but individual case reports of severe events have already emerged in the literature. 25 – 27 Rates of irAEs of grade 3–5 range from 1% to 9% across several Phase I and II studies released recently and appear to be lower than for other drugs in the ICI class, although this comparison also suffers from the limitations discussed above. 28 – 35 It will be important to revisit and confirm the irAE rates for these newer ICIs when data from larger Phase III trials become available.…”

“…Onset of events has been described as close to initiation of ICI therapy as 8 days, and as remote as >1 year, and the organ systems involved have included the central nervous system (CNS), cardiovascular system, musculoskeletal system, hepatic and renal systems, and even include myasthenia gravis, hemolytic anemia, sarcoidosis, and solid-organ transplant rejection. 25 – 27 , 36 – 80 Therefore, awareness of only the initial, commonly reported cases or a selection of scattered independent case reports is not sufficient to prepare clinicians for the immediate and long-term surveillance for these events that is required to effectively mitigate these toxicities among their patients.…”

Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors

“…However, the safety of this agent is still not fully guaranteed as its combination with other agents increased the potential toxicity. For example, an administered combination of durvalumab with a CTLA-4 inhibitor, tremelimumab, resulted in inflammatory myopathy in a 68-year-old NSCLC patient; fortunately, this adverse effect was resolved upon the discontinuation of this regimen [ 86 ].…”

Targeted Cancer Therapy and Its Ophthalmic Side Effects: A Review

“…Carrera reported a case of drug-induced mysositis in a patient with nonsmall-cell carcinoma treated with tremelimumab (anti-CTLA4) and durvalumab (anti-PD-L1). [60] Electromyography and muscle biopsy were suggestive of an ''inflammatory myopathy.'' Diplopia and ptosis improved upon drug cessation and oral steroid therapy.…”