Chronic adverse events more common than thought after adjuvant immunotherapy for melanoma
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Chronic immune-related adverse events appeared more common than previously thought among patients with stage III to stage IV melanoma who received adjuvant anti-PD-1 therapy, according to study results published in JAMA Oncology.
These events appeared to particularly affect non-visceral organs and included endocrinopathies, neurotoxicities and ocular events, according to the researchers.
“[Although] anti-PD-1 therapy has dramatically improved long-term outcomes for patients with melanoma, certain patients seem to have chronic side effects, seemingly more than reported in prior studies,” Douglas B. Johnson, MD, MSCI, assistant professor of medicine in the department of hematology and oncology at Vanderbilt University Medical Center, told Healio. “Oncologists should integrate the potential for chronic side effects into counseling about treatment options for patients with later-stage melanoma.”
Johnson and colleagues conducted a retrospective multicenter cohort study to examine the incidence, time course and spectrum of chronic immune-related adverse events associated with adjuvant anti-PD-1 therapy among 387 patients (median age, 63 years; 60.7% male) with stage III to stage IV melanoma receiving treatment across eight academic medical centers in the U.S. and Australia.
Most (74.9%) had preexisting comorbidities and 7.8% had autoimmune conditions. Moreover, 85.8% had tumors of cutaneous primary sites and 51.2% had BRAF/NRAS wild-type variants.
The majority (84.2%) of patients received nivolumab (Opdivo, Bristol Myers Squibb) and 15.8% received pembrolizumab (Keytruda, Merck). Median treatment duration was 306 days (range, 1-1,049).
Half of patients completed the treatment course, 25.3% discontinued treatment due to immune-related adverse events and 20.9% discontinued due to disease progression. Nearly 70% of patients did not experience disease recurrence, whereas 17.8% experienced metastatic recurrence and 12.9% had regional-only recurrence.
Median OS and RFS were not reached. Most patients (93%) remained alive at median follow-up of 529 days, and those who experienced acute or chronic immune-related adverse events had longer RFS than those who did not.
Overall, 69% of patients experienced an acute immune-related adverse event. Among them, 19.5% had grade 3 to grade 5 adverse events and two died, one of myocarditis and the other of neurotoxicity.
Chronic immune-related adverse events that persisted for more than 12 weeks after anti-PD-1 discontinuation occurred among 43.2% of patients. Of these, 96.4% were grade 1 or grade 2 and 85.6% persisted until final follow-up.
Immune-related adverse events that affected visceral organs appeared less likely to become chronic than endocrinopathies (73 of 88 cases; 83%), neurotoxicities (11 of 15 cases; 73.3%), ocular events (5 of 8 cases; 62.5%), xerostomia (9 of 17 cases; 52.9%) and arthritis (22 of 45 cases; 48.9%). Colitis became chronic in only 13.6% of cases (6 of 44), and 66.7% of those chronic cases resolved with extended follow-up.
Researchers observed no association of chronic immune-related adverse event development with age, sex, time of onset or need for steroids.
“Chronic side effects seemed more common than previously recognized, and involved organs including endocrine and salivary glands and joints and peripheral nerves. These toxicities usually had mild symptoms, though, and some improved over time,” Johnson said. “Further work should be done to study the impact of these toxicities on quality of life, and to determine how many side effects resolve with longer follow-up.”
For more information:
Douglas B. Johnson, MD, MSCI, can be reached at Vanderbilt University Medical Center, 2220 Pierce Ave., 777 PRB, Nashville, TN 37232; email: douglas.b.johnson@vumc.org.
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