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Patients with melanoma, autoimmune disorders require close monitoring with ipilimumab treatment
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Ipilimumab caused immune events and treatment-related adverse events among patients with preexisting autoimmune diseases and advanced melanoma, according to results of a retrospective review.
However, these autoimmune flares and adverse events were manageable with standard therapies. Thus, treatment with ipilimumab (Yervoy, Bristol-Myers Squibb) appeared feasible in this population with close monitoring, according to the researchers.
Douglas B. Johnson
Ipilimumab and other immunotherapies have been associated with immune-related adverse events, according to study background. The safety and efficacy of ipilimumab has not been studied in patients with preexisting autoimmune diseases.
Thus, Douglas B. Johnson, MD, MSCI, assistant professor of medicine at Vanderbilt-Ingram Cancer Center, and colleagues conducted a retrospective review to determine the safety profile and clinical activity of ipilimumab in this patient population.
The researchers evaluated data from 30 patients (57% men, median age, 59.5 years; range, 30-80) with advanced melanoma and an autoimmune disorder who received ipilimumab at one of nine academic tertiary referral centers between January 2012 and August 2015. Autoimmune disorders in the study population included rheumatoid arthritis (n = 6), psoriasis (n = 5), inflammatory bowel disease (n = 6), systemic lupus erythematosus (n = 2), multiple sclerosis (n = 2), autoimmune thyroiditis (n = 2) and other conditions (n = 7).
Safety — defined by the frequency of autoimmune flares and conventional immune-related adverse events — and efficacy served as the primary endpoints.
Forty-three percent of patients (n = 13) also received immunosuppressive therapy — most commonly with low-dose prednisone or hydroxychloroquine — at ipilimumab initiation.
Twenty-seven percent of patients (n = 8) experienced exacerbation of their autoimmune diseases, defined as recurrent or increased manifestations of prior symptoms. All of these patients received corticosteroids as treatment.
Disease exacerbation occurred 3 days to 7 months after the initiation of ipilimumab, but most frequently occurred 2 to 3 weeks (n = 3) and 6 weeks (n = 2) after the start of therapy.
Further, conventional grade 3 to grade 5 events occurred in 10 patients (33%). These events included colitis (n = 5), hypophysitis (n = 3), thyroiditis (n = 1) and acute glaucoma (n = 1).
Patients were mostly managed with corticosteroids; however, two patients received infliximab (Remicade, Janssen).
One patient with baseline psoriasis died of presumed immune-related colitis; however, researchers attributed this death to a delay in reporting symptoms.
Fifteen patients (50%) did not experience autoimmune flares or treatment-related adverse events.
Six patients (20%) achieved an objective response, including one patient with rheumatoid arthritis who achieved a durable complete response that is ongoing 2 years after therapy initiation.
Of the other five patients who achieved partial responses, one lasted 6 months; one lasted 9 months; and the others are ongoing at 3, 8 and 8 months.
Seven patients (23%) experienced rapid disease progression, and the median OS among these patients was shorter than 6 months.
In the entire cohort, median PFS was 3 months (95% CI, 2-8.3) and median OS was 12.5 months (95% CI, 6.4-not applicable).
The researchers acknowledged study limitations, including the potential underrepresentation of patients with severe autoimmune diseases. They further acknowledged the small sample size and the possibility of delayed treatment-related adverse events as other limitations.
“Clinicians may judiciously consider ipilimumab therapy in patients with advanced melanoma and baseline autoimmunity with close monitoring and adherence to immune-related adverse event treatment algorithms,” Johnson and colleagues wrote. “These insights are also important for other T-cell checkpoint inhibitors, which are now achieving regulatory approval in melanoma and other types of cancer.”
In an editor’s note, Mary L. Disis, MD, professor of medicine at University of Washington, as well as editor-in-chief of JAMA Oncology, suggested that these findings will influence the receipt of immunotherapies in patients thought to be at high risk for adverse events.
“These data underscore the safety of administering ipilimumab in patients with autoimmune disease,” Disis wrote. “The immune checkpoint inhibitor agents are associated with unique immune-related toxic effects that often make practicing oncologists hesitant to use the drugs. Repeated studies have shown that immune-related adverse events can be medically treated and serious toxicities prevented with vigilance to identify symptoms at an early stage in evolution. The same approach would be used with patients having concurrent autoimmune disease, as has been demonstrated by Johnson and colleagues, to ensure patient safety.” – by Cameron Kelsall
Disclosure: Johnson reports a consultant role with Bristol-Myers Squibb and Genoptix. Please see the full study for a list of all other researchers’ relevant financial disclosures. Disis reports research funding from Celgene, EMD Serono, Seattle Genetics and VentiRx, as well as stock ownership in EpiThany and VentiRx.
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