medwireNews: In patients receiving anti-programmed cell death protein 1 (PD-1) inhibitors for advanced non-small-cell lung cancer (NSCLC), the presence of certain autoimmune antibodies prior to treatment is associated with both clinical benefit and immune-related adverse events (irAEs), research indicates.
Therefore, “these autoimmune markers may help determine the risk-benefit ratio for individual patients with NSCLC, maximizing therapeutic benefits while minimizing irAEs”, say Shunichi Sugawara and fellow investigators, from Sendai Kousei Hospital in Japan.
They analysed the medical records of 137 patients with subclinical disease who were treated with the PD-1 inhibitors nivolumab (72%) or pembrolizumab (28%) between January 2016 and January 2018. Forty-eight percent of the patients developed an irAE within a median of 4.7 weeks.
Patients whose pretreatment blood samples tested positive for rheumatoid factor, antinuclear or antithyroid antibodies had a significantly higher objective response rate (ORR) and disease control rate (DCR) than those who tested negative, at 41% versus 18% and 81% versus 54%, respectively.
Progression-free survival (PFS) was also significantly better for patients with versus without pre-existing antibodies, at a median of 6.5 and 3.5 months, respectively, which gave a hazard ratio for disease progression or death of 0.53.
Interestingly, there was no significant difference in the ORR and DCR when patients were categorised by the type of antibody, but the improvement in PFS appeared to be driven mainly by a significant difference between patients who were positive for rheumatoid factor and those who were negative, with corresponding median values of 10.1 and 3.7 months.
There was no significant difference in overall survival between patients with autoimmune antibodies and those without, although the median duration was numerically greater in the former group, at 17.6 and 14.6 months, respectively.
As reported in JAMA Oncology, patients with pre-existing antibodies were significantly more likely to experience any-grade irAEs relative to their counterparts without antibodies, with rates of 60% versus 32%, but the incidence of irAEs of grade 3 or worse was comparable.
Skin reactions of any grade were significantly more common in patients with versus without rheumatoid factor positivity (47 vs 24%), and the incidence of thyroid dysfunction was significantly higher among those with versus without antithyroid antibodies (20 vs 1%). But there was no significant difference between any of the groups with regard to the incidence of pneumonitis, hepatitis, myositis or peripheral neuropathy.
Shunichi Sugawara and colleagues note several limitations of their study, including the small sample size and the retrospective nature of the analysis.
Additionally, “[t]he duration of immunotherapy in the hospital or at follow-up may also be a potential confounder because immunologic toxicity may be more likely to develop in patients subjected to longer immune checkpoint inhibitor exposure”, they say.
“Nevertheless, 46 of 66 patients (70%) who developed irAEs presented symptoms within 8 weeks from the start of nivolumab or pembrolizumab monotherapy, suggesting that the observed events were unlikely to be due to higher risk of toxicity from longer therapy periods”, the team writes.
Toi Y, Sugawara S, Sugisaka J, et al. Profiling preexisting antibodies in patients treated with anti–PD-1 therapy for advanced non–small cell lung cancer. JAMA Oncol; Advance online publication 27 December 2018. doi: 10.1001/jamaoncol.2018.5860
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