Safety and efficacy of concurrent administration of influenza vaccine in patients undergoing anti-PD-1 immunotherapy.

Abstract

e14607 Background: Concerns have been raised over administration of influenza vaccination concurrent with immune checkpoint inhibitor therapy, specifically, implication in induction of Guillain-Barre syndrome. The aim of this study is to assess the safety and efficacy of influenza vaccination in patients undergoing anti-PD1 therapy. Methods: This is a prospective observational study evaluating the safety and efficacy of Afluria (Seqirus) in patients receiving anti-PD1 therapy. Antibody titers against common influenza A and B antigens were measured by a semi-quantitative ELISA on days 0, 45 and 90+ post vaccine administration to confirm anti-PD1 therapy did not interfere with anti-influenza humoral responses. Influenza infection, confirmed by rapid antigen testing, and influenza-related hospitalizations were reported among vaccinated patients. Safety was assessed using the FDA toxicity grading scale for clinical trials. Results: The acute humoral responses and subsequent IgG responses of the 28 patients included in this study are as follows in the table. IgM responses at 45 days to both influenza A and B common antigens were statistically significant (all P<0.05*). IgG response to common influenza B antigens was increased at day 45 ( P=0.001*). One of 28 patients contracted influenza B infection, confirmed by rapid antigen testing. There were no influenza-related hospitalizations. One patient had a grade 2 local adverse event (AE). A second patient had both a grade 2 local and a grade 2 systemic AE (myalgia). No grade 3/4 local or systemic AEs were reported. Conclusions: Administration of influenza vaccination concurrent with anti-PD1 therapy appeared safe in our study. No grade 3/4 local or systemic AEs were noted. Anti-PD1 therapy did not adversely affect anti-influenza humoral responses. Our data demonstrate that the increase in IgM reactivity to common influenza A and B antigens appears to be an immediate reaction to revaccination. Seroprotection can be inferred by documented infection in only one patient and absence of influenza related-hospitalizations. [Table: see text]

Immune-mediated adverse events following influenza vaccine in cancer patients receiving immune checkpoint inhibitors

“…In addition to our case series, several studies have been published in abstract/poster or full manuscript form over the previous 12 months (Table 5). [7][8][9][10] Vaccine efficacy has been evaluated in ICI patient populations as well. In a phase II trial, most vaccinated patients who were receiving ipilimumab demonstrated increased antibody levels to influenza B, A/H1N1/H3H2 antigens compared to nonvaccinated patients, suggesting that an appropriate immunization response can be achieved in patients receiving CTLA-4 inhibitors.…”

“…11 However, this study did not report on post-vaccination adverse events. Kanaloupitis et al 9 performed a prospective observational study evaluating the safety and efficacy of IIV (Afluria) in 28 patients who had received anti-PD-1 therapies. Antibody titers against common influenza A and B antigens were measured by a semi-quantitative ELISA on days 0, 45, and 90 + post vaccine were performed.…”

“…6 Until recently, there has been a scarcity of information investigating concurrent ICI therapy with the administration of influenza vaccination. [7][8][9][10] Ipilimumab, a fully humanized monoclonal antibody that blocks CTLA-4, has demonstrated improved survival in metastatic melanoma. 11 Similarly, the PD-1/ PD-L1 inhibitors, either alone or in combination with ipilimumab, have significantly improved patient survival and outcomes in numerous solid tumor malignancies.…”

Recommendation for the diagnosis and management of immune checkpoint inhibitor related infections

“…34 On the contrary, another study suggested that it was safe to use inactivated vaccines for patients receiving PD-1/PD-L1 inhibitors. 35 Therefore, potential risks and benefits should be carefully evaluated before vaccination.…”

“…One study reported increased frequency of irAEs after treatment with inactivated influenza vaccines in cancer patients treated during PD‐1 blockage . On the contrary, another study suggested that it was safe to use inactivated vaccines for patients receiving PD‐1/PD‐L1 inhibitors . Therefore, potential risks and benefits should be carefully evaluated before vaccination. Combined use of ipilimumab and PD‐1 inhibitors was associated with a higher rate of irAEs compared with ipilimumab or PD‐1 inhibitor monotherapy …”