Correlation between BNT162b2 mRNA Covid-19 vaccine-associated hypermetabolic lymphadenopathy and humoral immunity in patients with hematologic malignancy

Abstract

Purpose Vaccine-associated hypermetabolic lymphadenopathy (VAHL) is frequently observed on [ 18 F]FDG PET-CT following BNT162b2 administration. Recent data suggest a prominent B cell germinal-center (GC) response elicited by mRNA vaccines in draining lymph nodes. Thus, in this study we aimed to explore the correlation between VAHL and humoral immunity as reflected by post-vaccination serologic testing and by comparing the incidence of VAHL between lymphoma patients treated recently with B cell depleting therapy and those that were not. Methods A total of 137 patients with hematologic malignancy that had post-vaccination [ 18 F]FDG PET-CT were included (All-PET group), 86 received both vaccine doses before imaging (PET-2 group). Their VAHL status and grade on imaging were recorded. Among 102 lymphoma patients, 34 (33.3%) were treated during the year prior vaccination with anti-CD20 antibody containing therapy. A subgroup of 54 patients also underwent serologic testing 2–3 weeks after the booster dose, and their anti-spike titers were recorded and graded as well. Results The overall incidence of VAHL in patients with hematologic malignancy was 31.4%. The 34 lymphoma patients treated during the year prior vaccination with anti-CD20 antibody containing therapy had significantly lower rates of VAHL comparted with all other lymphoma patients (8.8 versus 41.2% in all-PET patients, Pv < 0.01). VAHL rates were 10% in patients with negative serology, 31.3% in patients with low anti-spike titers, and 72.2% in patients with high anti-spike titers. The positive predictive values of VAHL were 90 and 93.3% in all-PET and PET-2 patients, respectively. A positive statistically significant correlation was found between VAHL and serology ranks in All-PET patients (r s = 0.530, Pv < 0.001), and stronger correlation was found in PET-2 patients (r s = 0.642, Pv < 0.001). Conclusion VAHL on [ 18 F]FDG PET-CT of patients with hematologic malignancy may reflect GC B cell proliferation and an effective humoral response elicited by BNT162b2 vaccine.

A sigh of relief: vaccine-associated hypermetabolic lymphadenopathy following the third COVID-19 vaccine dose is short in duration and uncommonly interferes with the interpretation of [18F]FDG PET-CT studies performed in oncologic patients

“…The previously described association between VAHL and immunogenicity [14,15] may be implied also in the results of the current study. Older age [17] and obesity [18] were both reported to be associated with weaker vaccine-induced immunity.…”

“…Older age [17] and obesity [18] were both reported to be associated with weaker vaccine-induced immunity. The results of the current study that younger age and lower BMI are independent predictors of high-grade VAHL (which correlates with humoral immunity [14]) further strengthen the association between VAHL and the vaccine-induced immunity.…”

“…In a study our group conducted on patients with hematologic malignancy, we presented the positive correlation between the imaging finding of VAHL and the post-vaccination antibody titers. We concluded that VAHL on imaging may reflect a potent germinal center response in lymph nodes draining the vaccine injection site [14]. The relationship between VAHL and immune status was observed by Eifer et al as well [15].…”

“…VAHL, vaccine-associated hypermetabolic lymphadenopathy; BMI, body mass index. Active malignancy, this variable was considered positive in cases of treatment-naïve patients, those who received recent anti-cancer therapy, and those with recurrent disease identified on their [ 18 [14][15][16]. However, VAHL cases following the third dose were found to have shorter duration and low uptake intensity after the first 5 days from vaccination.…”

Assessing immune response upon systemic RNA vaccination on [18F]-FDG PET/CT for COVID-19 vaccine and then for immuno-oncology?

“…For instance, a rapid and transient increase in spleen glucose metabolism after RNA cancer vaccine connotes robust immune activation and T-cell proliferation [5]. The same argument can be made for hypermetabolic draining lymph nodes, which could reflect a prominent B cell germinal center activation and an effective humoral response elicited by mRNA vaccine [6].…”