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Pembrolizumab for melanoma may cause antiphospholipid syndrome
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Antiphospholipid syndrome occurred following treatment with pembrolizumab for unresectable, stage IIIB melanoma, according to a research letter.
Despite the efficacy of anti-PD-1 agents for melanoma, immune-related adverse events — such as those affecting the skin, gastrointestinal tract, and hepatic and endocrine systems — can occur.
“Antiphospholipid syndrome [APS] has been reported in patients with advanced melanoma treated with alfa-2b interferon alone, or combined with anti-interleukin 2,” Adrien Sanchez, MD, of the department of dermatology at Archet Hospital at Nice University Hospital in France, and colleagues wrote. “We report the first case to our knowledge of APS following treatment with pembrolizumab [Keytruda, Merck] alone. The presence of both a clinical criterion (secondary Raynaud phenomenon, or microthrombosis) and an immunologic criterion (high levels of antiphospholipid antibodies) led to the diagnosis of APS.”
This case involved a woman aged in her 60s who presented with superficial spreading melanoma on her right calf, with a Breslow thickness of 3.15 mm and no ulceration. She underwent multiple surgeries for recurrent node metastases over 3 years. Although molecular testing did not detect a BRAF V600 mutation, PET/CT results showed a novel metastasis in the left inguinal area.
Clinicians treated the patient with 2 mg/kg pembrolizumab every 3 weeks. Despite a partial response within 3 months, bilateral secondary Raynaud phenomenon developed in her fingers after the 10th infusion. A necrotic lesion then appeared on one of her fingertips.
The patient had no personal or familial history of primary Raynaud phenomenon, the researchers wrote.
Researchers observed anticardiolipin antibodies and lupus anticoagulants in lab analyses, but beta-2 glycoprotein 1 antibodies were not elevated. Other lab parameters ranging from fibrinogen to antithrombin activity appeared negative or normal, as did Doppler ultrasound of the upper extremities.
Clinicians diagnosed APS based on clinical observations. The patient discontinued pembrolizumab and commended prednisolone 1 mg/kg per day for 1 month. This treatment resolved Raynaud phenomenon and the necrotic lesion, researchers wrote.
Ten months after the initial pembrolizumab dose, another PET/CT scan revealed one hypermetabolic right external iliac lymph node, which was treated with stereotaxic radiotherapy. Raynaud phenomenon did not recur through the last follow-up.
Researchers noted that associations with APS have also been reported for ipilimumab (Yervoy, Bristol-Myers Squibb) and nivolumab (Opdivo, Bristol-Myers Squibb).
“Antiphospholipid antibodies are known to be associated with cancer,” the researchers wrote. “Although paraneoplastic APS cannot be ruled out, the chronological association between treatment with a known immunostimulant such as pembrolizumab and the development of APS, as well as the well-controlled extensive melanoma in the present case, are arguments for pembrolizumab-induced APS. In addition, a complete resolution of the symptoms was rapidly seen after pembrolizumab treatment was stopped.”
The researchers concluded that clinicians should be aware of these associations as use of anti-PD-1 therapies increases. – by Rob Volansky
Disclosures: The researchers report no relevant financial disclosures.
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