Immune-Related Adverse Events Occurring After 2 Years of Anti–PD-1 Therapy Are Common

Long-term immune-related adverse events are frequent in patients with melanoma being treated with anti–PD-1 antibodies. These events occur more often in those who already experience an immune-related adverse event within the first 2 years of treatment, according to a poster presentation during the 2020 American Society of Clinical Oncology Virtual Scientific Meeting.

In reviewing the records of patients with melanoma who received anti–PD-1 therapy for ≥2 years, researchers led by Charlée Nardin, MD, Dermatology, Centre Hospitalier Universitaire de Besançon, Besançon, France, found that 43% of patients experienced immune-related adverse events after 2 years on treatment.

For the study, the researchers examined MelBase, a French multicentric biobank dedicated to the prospective follow-up of adults with unresectable stage III or IV melanoma. They identified 119 patients who were treated with anti–PD-1 monotherapy for ≥2 years, with a median follow-up of 41.7 months. Fifty-three patients were being treated with nivolumab (Opdivo) and 66 with pembrolizumab (Keytruda), with a median time of treatment of 35 months.

At treatment initiation, 84% had American Joint Committee on Cancer stage IV melanoma, 11% had a history of autoimmune disease, 72% had BRAF wild-type disease, 22% had brain metastases, and 56% had a normal lactate dehydrogenase level.

Immune-related adverse events occurred in 99 (83%) patients at a median of 13.3 months, with 30 patients experiencing grade 3 or 4 immune-related adverse events.

Late-onset immune-related adverse events occurred in 51 (43%) patients and were mostly grades 1 and 2. Among the most common grade 1-2 late-onset events were cutaneous adverse events (41 events in 27 patients), gastrointestinal adverse events (27 events in 15 patients), general adverse events (26 events in 17 patients), and neuromuscular adverse events (10 events in 9 patients). There were 4 late-onset grade 3 or 4 adverse events in 4 patients (1 each of cutaneous, endocrine, immune system disorder, and neuromuscular adverse events).

Among the patients with late-onset adverse events, 45 (87%) patients previously experienced an immune-related adverse event within the first 2 years of anti–PD-1 therapy, 29 (56%) patients experienced multiple immune-related adverse events, and 8 (16%) had late-onset adverse events after treatment interruption.

“Further studies are needed to understand the mechanisms of late-onset adverse events due to anti–PD-1 therapy and to establish the optimal time to treat melanoma patients with anti–PD-1 therapy,” the researchers advised.


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