Chronic immune-related adverse events common after anti-PD-1 therapy for melanoma
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Key takeaways:
- Nearly two-thirds of patients experienced acute immune-related adverse events.
- The most common persistent chronic adverse events included hypothyroid, arthritis dermatitis and adrenal insufficiency.
Chronic immune-associated adverse events appeared common after treatment with adjuvant anti-PD-1 therapy among patients with melanoma, according to study results published in JAMA Network Open.
The findings highlight the need for long-term monitoring and management of adverse events in this patient population, researchers concluded.
Rationale and methodology
Adjuvant anti-PD-1 therapy improves RFS among patients with high-risk resected melanoma but may lead to potentially chronic immune-related adverse events, according to study background.
“We observed that a subset of patients had long-term and chronic toxicities after receiving immune checkpoint inhibitors,” Douglas B. Johnson, MD, MSCI, associate professor of medicine and chief of the solid tumor section in the division of hematology/oncology at Vanderbilt University Medical Center, told Healio.
“[We] wanted to quantify the percentage of patients affected and which organ systems were most often involved.”
Researchers sought to determine the incidence, characteristics and long-term outcomes of chronic immune-related adverse events associated with use of adjuvant anti-PD-1 therapy among patients with advanced or metastatic melanoma.
The analysis included 318 patients (median age, 61 years; 59.7% male; 84.9% cutaneous primary; 74.5% stage IIIB or stage IIIC) treated at one of six institutions in the U.S. and Australia between 2015 and 2022.
Main outcomes included incidence, spectrum and ultimate resolution vs. persistence of chronic immune-related adverse events, defined as those that persisted at least 3 months after therapy cessation.
Findings
Nearly two-thirds (63.7%) of patients experienced acute immune-related adverse events during treatment, and 13.8% experienced grade 3 to grade 5 adverse events.
Nearly half (46.2%) of patients experienced chronic immune-related adverse events that persisted for at least 3 months after therapy cessation. Of these, 50.3% were grade 2 or higher, 4.1% were grade 3 to grade 5, and 68% were symptomatic.
At median follow-up of 1,057 days, 36.7% of patients (n = 54) experienced resolution of chronic adverse events, with median time to resolution of 19.7 months from initiation of anti-PD-1 therapy and 11.2 months from anti-PD-1 cessation.
Among the 29.2% of patients in the original cohort with persistent immune-associated adverse events present at last follow-up, 59.1% were grade 2 or higher, 44.1% were symptomatic, 25.8% required use of therapeutic systemic steroids and 45.2% required other management.
Of the 54 patients who experienced resolution of chronic adverse events, the most common persistent chronic adverse events included hypothyroid (70.4%), arthritis (33.3%), dermatitis (16.7%) and adrenal insufficiency (14.8%). In addition, 17% of patients experienced persistent endocrinopathies, 15.1% experienced nonendocrinopathies and 2.8% experienced both.
Among the 37 patients who experienced chronic immune-associated adverse events who received additional immunotherapy, 67.6% experienced no effect on chronic immune-related adverse events and 32.4% experienced increased chronic toxicity.
Researchers acknowledged study limitations, including the potential review of toxic effects and adverse events using clinical data and notes that may lack the fidelity of formal clinical trial adverse event reporting. In addition, documentation may not have mentioned every toxicity in every note, thus lowering the fidelity of the resolution date for individual patients.
Implications
The findings suggest clinicians should consider the risks for these toxicities and monitor patients after they complete their treatment course, Johnson told Healio.
“We are currently conducting more studies to identify patients at risk for severe and chronic toxicities, and to identify other long-term effects of immune checkpoint inhibitors,” he said.
References:
- Chronic complications from immunotherapies more prevalent and persistent than previously shown among melanoma survivors (press release). Available at: https://news.vumc.org/2023/08/08/chronic-complications-from-immunotherapies-more-prevalent-and-persistent-than-previously-shown-among-melanoma-survivors/. Published, Aug. 8, 2023. Accessed, Aug. 17, 2023.
- Goodman RS, et al. JAMA Netw Open. 2023;doi:10.1001/jamanetworkopen.2023.27145.
For more information:
Douglas B. Johnson, MD, MSCI, can be reached at douglas.b.johnson@vumc.org.
Perspective
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Lucy Boyce Kennedy, MD
This study examined the incidence of chronic immune-related adverse events (irAEs) among patients who received adjuvant anti-PD-1 therapy for melanoma. Nearly half of patients experienced irAEs, which persisted for at least 3 months after stopping treatment. Chronic irAEs could involve multiple organs, including thyroid, joints, skin and adrenal glands. This study highlights multiple areas of unmet need in our management of patients receiving checkpoint inhibitors.Anti-PD-1 antibodies are widely used across solid tumor oncology, with diverse indications in adjuvant and unresectable settings. This study describes the potential long-term impact of these therapies, highlighting the oncologist’s responsibility to focus not only on oncologic outcomes but also on survivorship and the potential for long-term toxicity. As more patients receive checkpoint inhibitors, and as prognosis improves for multiple tumor types, there is a need for education regarding survivorship and long-term toxicity. This is true not only for the oncology team, but also for other providers who will interact with our patients, including primary care and subspecialists — such as endocrinologists, rheumatologists and dermatologists — who will partner with us in taking care of these patients.
Another area of unmet need is improvement in our tools to predict risk among patients receiving checkpoint inhibitors. Multiple studies have sought to identify biomarkers to characterize risk for irAEs; however, at this time, there are no biomarkers measured in routine clinical practice to assess the risk that an individual patient will develop an irAE. There is a need for validated biomarkers to assist with irAE risk assessment among patients who will receive checkpoint inhibitors. As this study indicates, there is potential for chronic irAEs, which may lead to persistent symptoms or a requirement for ongoing medication use. Tools to assess this risk more accurately will allow us to provide more individualized counseling to our patients prior to starting checkpoint inhibitors and will facilitate shared decision-making.
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