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 [18F]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 did not. Methods: A total of 137 patients with hematologic malignancy that had post-vaccination [18F]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 to 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 (rs = 0.530, Pv < 0.001), and stronger correlation was found in PET-2 patients (rs = 0.642, Pv < 0.001).Conclusion: VAHL on [18F]FDG PET-CT of patients with hematologic malignancy may reflect GC B-cell proliferation and an effective humoral response elicited by BNT162b2 vaccine.

Lessons Learned from Post–COVID-19 Vaccination PET/CT Studies

“…The frequency of FDG avid LA was higher after the second vaccination compared to the first, in present study 69% vs 55% respectively, compared to 53.9% and 36.4% (9), 43.3% and 14.5% (12), respectively, in recent publications. The prevalence of LA with benign CT appearances and low-grade FDG accumulation was also similar, 77% in present study compared to 80.1% in previous study (9). This is significantly higher in comparison to axillary LA post H1V1 influenza A virus vaccination (15) which was observed in 29.3 % (13,15) and to post papilloma virus vaccination (17), probably due to the high immunogenicity of the COVID-19 vaccine.…”

“…Stand-alone axillary LA can be challenging in cases of lymphoma, breast cancer, melanoma, or other cutaneous malignancies. In present study we have demonstrated FDG avid LA in 59% of patients following vaccination for COVID-19 compared to 45-46 % in recent publications (9,10). The frequency of FDG avid LA was higher after the second vaccination compared to the first, in present study 69% vs 55% respectively, compared to 53.9% and 36.4% (9), 43.3% and 14.5% (12), respectively, in recent publications.…”

“…In these cases the radiological appearances of the LA play a crucial role. In most cases benign and malignant lymph nodes can be separated with only 8% defined as equivocal in present study and 14.8% in another study (9). Familiarity with post-vaccination pattern on PET/CT is important for the interpreting as well as referring physicians.…”

“…All studies have reported regression in FDG activity in LA and at the injection site. Table 5 summarizes the main PET/CT findings post COVID-19 vaccination in recent publications (9)(10)(11)(12).…”

“…Incidental LA on physical examination, mammography, breast MRI or PET/CT challenged interpretation of these studies (6,7,8). Several studies recently published demonstrated increased FDG uptake in post COVID-19 vaccination LA (9)(10)(11)(12).…”