This is a 76-year-old woman, former heavy smoker with history of Hashimoto’s thyroiditis and breast cancer in remission. She was diagnosed with dermatomyositis in 2015 when she developed a heliotrope rash. As part of the paraneoplastic workup, she underwent imaging which revealed a left lung mass and abdominal lymphadenopathy. Biopsy of lung mass was consistent with non-small cell lung cancer (NSCLC). Patient received 6 cycles of carboplatin and gemcitabine but had disease progression. An immunotherapeutic agent called Nivolumab was initiated in September 2016 and she completed 3 cycles. As a consequence, she was admitted to the hospital in October 2016, with debilitating, progressive proximal upper and lower extremity weakness and tenderness most notably in the right shoulder. Her right shoulder x-ray was unremarkable. Labs revealed an elevated creatinine kinase (CK) level of 1220 (U/L) and thyroid-stimulating hormone (TSH) of 24.6 (uIU/ml). These values were normal 10 months ago. She was admitted for a dermatomyositis flare and uncontrolled hypothyroidism. Rheumatology and Endocrinology consultations assessed that Nivolumab was likely the inciting agent for flare-ups of her autoimmune conditions. Methylprednisolone 1mg/kg was started and levothyroxine dose was increased. Patient’s condition improved significantly since admission. She was transitioned to prednisone and discharged to a rehabilitation facility. Outpatient labs one month later revealed normal TSH and CK levels of 5.34 (uIU/ml) and 446 (U/L) respectively.
Discussion:
Checkpoint inhibitors have emerged as new agents in treatment of cancer. Since 2011, the FDA has approved three immune checkpoint inhibitors (Ipilimumab, Pembrolizumab, and Nivolumab) for advanced melanoma and metastatic NSCLC. Nivolumab is an anti-PD1 antibody and was approved by the FDA in 2014. These agents compared to conventional therapies have shown greater survival benefit through up-regulation of anti-tumoral immune response. However, they can also cause aberrant immune activation leading to undesirable off-target inflammation and severe immunotherapy-related adverse events (irAEs). In a recent study that reviewed 250 cases of patients on immunotherapy, Nivolumab was implicated primarily in autoimmune thyroid disease and pneumonitis.1 Another study looked at adverse effects of immunotherapy in patients with pre-existing autoimmune disorders (AD) and found 20 out of 52 patients experienced a flare of AD requiring immunosuppression.2 Our case demonstrates a patient with dermatomyositis and hypothyroidism who experienced exacerbation of both conditions after initiation of Nivolumab.
Conclusions:
With the emerging immunotherapy agents in the field oncology, it is important for a physician to be aware of their side effects. Potential toxicities have been reported for almost every organ system. The main stay treatment for irAEs is steroids and discontinuation of immunotherapy agent.