RESUMO
Cancer patients frequently receive immune checkpoint therapies (ICT) which may modulate immune responses to COVID-19 vaccines. Recently, cytokine release syndrome (CRS) was observed in a cancer patient who received the BTN162b2 vaccine under ICT. Here, we analyzed adverse events (AEs) in patients of various solid tumor types undergoing (n=64) or not undergoing (n=26) COVID-19 vaccination under ICT as an exploratory endpoint of a prospectively planned cohort study. We did not observe clinically relevant CRS after vaccination (95% CI [0,0.056]). Short term (<4 weeks) serious AEs were rare (12.5%) and overall AEs under ICT were comparable to unvaccinated patients. Despite the absence of CRS symptoms, we observed a pairwise-correlated set of CRS-associated cytokines upregulated in 42% of patients after vaccination and ICT (>1.5fold). Hence, clinically meaningful CRS appears to be rare in cancer patients under ICT and elevated serum cytokine levels are common but not sufficient to establish CRS diagnosis.
RESUMO
Triple-negative breast cancer (TNBC) is typically treated with chemotherapeutic agents, including carboplatin (Cb), an DNA platinating agent. The O6-methylguanine-DNA-methyltransferase gene (MGMT) encodes for the protein O6-alkylguanine-DNA-alkyltransferase (MGMT protein). MGMT protein is involved in DNA repair mechanisms to remove mutagenic and cytotoxic adducts from O6-guanine in DNA. In glioblastoma multiforme, MGMT methylation status is a predictive biomarker for increased response to temozolomide therapy. It has been suggested, that MGMT protein may have relevance for cellular adaptation and could have an influence on resistance to carboplatin therapy. We investigated the influence of MGMT promoter methylation on pathologic complete response and survival of patients with TNBC treated in the neoadjuvant GeparSixto trial. In 174 of 210 available TNBC tumors a valid MGMT promoter methylation status was determined by pyrosequencing of 5 CpG islands. In 21.8%, we detected a mean MGMT promoter methylation >10%. Overall, MGMT promoter methylation was not significantly associated with pathological complete response (pCR) rate. After stratification for the two therapy arms with and without Cb no statistically significant differences in therapy response rates between the two MGMT promoter methylation groups could be observed. Our results show that different MGMT promoter methylation status is not related to different chemotherapy response rates in the TNBC setting in GeparSixto.
