Patient experiences angioedema with pembrolizumab treatment

Key takeaways:

• The patient received immunotherapy for squamous cell carcinoma.
• The patient was admitted for facial swelling three times in 2 months.
• Symptoms did not return with a switch to a different immunotherapy.

BOSTON — Physicians suspect the solvent used in the administration of pembrolizumab may have triggered recurrent angioedema for a patient with squamous cell carcinoma, according to a poster presented at the CHEST Annual Meeting.

Pembrolizumab (Keytruda Merck) is widely used in treating malignancies, with rare instances of angioedema, Jenish Bhandari, MBBS, resident, division of medicine, State University of New York Upstate Medical University, and colleagues wrote.

The patient in this case was a man, aged 58 years, who had chemoradiation and surgical resection for recurrent stage IVa squamous cell carcinoma on his tongue, followed by maintenance therapy with pembrolizumab.

“After initiation of this treatment, in about 4 months, the patient started developing some numbness around his mouth, subjective shortness of breath,” Bhandari told Healio. “This episode was recurrent.”

The patient also experienced three episodes of facial swelling within a span of 2 months, including the closure of his right eye, in addition to mild swelling on his arms and legs. There were no rashes or prurits.

“The last episode was so severe that he had to seek medical attention,” Bhandari said. “When he was evaluated in the ED, there was a concern for airway compromise.”

The patient was admitted, and treatment began with methylprednisolone, and dexamethasone, famotidine and Benadryl (Johnson & Johnson) followed. Physicians also closely monitored him for airway compromise and administered bedside heliox, a helium and oxygen mixture.

The patient did not have soft tissue to hold a trach in place, so the physicians did not consider him a candidate for a tracheostomy. Also, the authors noted that his tumor burden increased the risk for seeding, so intubation would have been difficult.

“But luckily, things started heading in the right direction after the medications,” Bhandari said.

The patient did not receive any pembrolizumab while he was admitted. Instead, he received a different programmed death-1 (PD-1) inhibitor.

“And that never happened again,” Bhandari said.

The physicians engaged in shared decisionmaking with the patient before making the switch.

“He needed immunotherapy to maintain his cancer-free time,” Bhandari said. “It was a risk-benefit discussion with the patient, and the patient opted to be on therapy.”

The authors noted that the mechanism behind these rare cases of angioedema induced by pembrolizumab is not entirely understood but the immune modulation that PD-1 inhibition exerts may be related to it.

“There was a lot of thought about what could have potentially caused it,” Bhandari said.

Specifically, the authors said, dysregulated inflammatory responses may result from the T-cell activation and cytokine release enhanced by the PD-1 blockade. Like other immune-mediated hypersensitivity reactions, the authors continued, angioedema could be triggered by this excessive immune activation via nonallergic pathways.

Bhandari also said that pembrolizumab itself might not be responsible for the angioedema. Instead, the solvent that delivers the pembrolizumab might be the trigger.

“That is what we have seen with other drugs too,” he said. “We labeled this solvent as a potential allergen for this patient.”

The pharmacy then would be aware that it should not use this solvent for other drugs, Bhandari said.

Overall, the authors said that angioedema has occurred shortly after pembrolizumab has begun as well as after several treatment cycles, indicating that physicians should maintain a high level of suspicion when patients on the immunotherapy present with facial swelling, lip or tongue enlargement or respiratory symptoms.

When patients present with these symptoms, physicians should discontinue the drug immediately and provide supportive measures such as corticosteroids and antihistamines to prevent compromise of the airway, the authors said.

The authors also emphasized that it is important for physicians to be vigilant as they monitor patients who are receiving immune checkpoint inhibitors for uncommon side effects and added that additional research into the pathophysiology and management of angioedema due to pembrolizumab is necessary.

“These are the mainstay drugs for cancer patients,” Bhandari said. “More studies need to be done regarding the exact pathophysiology and potential side effects of these medications.”

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