Real-world data confirm that the combination of ipilimumab (Yervoy) and anti–PD-1 therapy has efficacy comparable to that shown in clinical trials in patients with preexisting autoimmune disorders and advanced melanoma, without an increased frequency of immune-related adverse events. The risk of a flare of autoimmune disease, however, is substantial.
Clinical data obtained from 10 international centers demonstrated an objective response rate (ORR) of 55%, including an ORR of 44% in patients with a flare of their autoimmune disease, reported Australian researchers led by Lauren J. Brown, MBBS, Crown Princess Mary Cancer Care Centre, Westmead, New South Wales, Sydney.
“Clinicians may consider the use of combination immunotherapy for patients with pre-existing autoimmune disease. However, in patients with inflammatory bowel disease and rheumatologic conditions, the risk of severe flare is significant,” they concluded in their poster presented during the American Society of Clinical Oncology 2020 Virtual Scientific Program.
Clinical trials of immunotherapy typically exclude patients with preexisting autoimmune disease, they noted.
In their retrospective analysis, they identified 55 patients with a preexisting autoimmune disorder and unresectable stage III or IV melanoma who received ≥1 doses of the combination of ipilimumab and an anti–PD-1 agent. Forty-six patients were treated with ipilimumab plus nivolumab (Opdivo) and 9 with ipilimumab plus pembrolizumab (Keytruda). Forty (73%) patients received 3 mg/kg of ipilimumab whereas 15 (27%) received a lower dose. Nine patients received previous anti–PD-1 therapy with no flares of their autoimmune disorder when on single-agent anti–PD-1.
Preexisting autoimmune disorders were endocrine-related in 19 (35%) patients, gastrointestinal in 14 (25%), rheumatologic in 11 (20%), dermatologic in 7 (13%), neurologic in 2 (4%), hematologic in 1 (2%), and “other” in 2 (4%). Ten patients had active symptoms of autoimmune disease and 13 were immunosuppressed before staring ipilimumab plus anti–PD-1 treatment.
Thirty-seven (67%) patients experienced an immune-related adverse event unrelated to their autoimmune disorder, 38% being grade ≥3, and 15 of the 37 (41%) stopped both agents after immune-related adverse events. “This demonstrated no increased rate of toxicity compared with the clinical trial population of the CheckMate-067 trial,” said Dr Brown.
Eighteen (33%) patients had a flare of their autoimmune disorder at a median of 19 days: 11 (61%) had grade-1 or -2 flares, 5 (28%) had grade-3 flares, and 2 (11%) had grade-4 flares. By autoimmune disease subtype, 7 of 11 patients (64%) with rheumatologic disease had flares, 5 of 14 (36%) with a gastrointestinal autoimmune disorder, and 2 of 19 (11%) with an endocrine disorder.
The risk for flare was higher in those patients with clinically active disease (5 of 10; 50%) and on immunosuppression prior to receipt of dual immunotherapy (7 of 13; 54%).
Median progression-free survival in patients without flare was 9 months, compared with 2.6 months in those with flare (P = .047).
Oral steroids were used to manage flares in 4 (22%) patients, intravenous steroids in 3 (17%), and steroids and steroid-sparing agents in 6 (33%). Seven of the 18 patients who experienced a flare of their autoimmune disorder required hospitalization to manage the flare, and 2 patients required intensive care for severe inflammatory bowel disease flare. Eight patients stopped combination treatment due to the flare.
After the flare, 5 of the 18 patients (26%) stopped both immuno-oncology drugs, 3 (17%) patients had dosage interruption and continuation of their anti–PD-1 therapy, 7 (39%) patients continued both immuno-oncology agents, and 3 (17%) patients stopped therapy due to disease progression.
Source: Brown LJ, Weppler A, Bhave P, et al. Combination anti-PD1 and ipilimumab (ipi) therapy in patients with advanced melanoma and pre-existing autoimmune disorders (AD). J Clin Oncol. 2020;38(15_suppl). Abstract 10026.