Changes in haemostasis and inflammatory markers after mRNA BNT162b2 and vector Ad26.CoV2.S SARS-CoV-2 vaccination.

INTRODUCTION: Reported thromboembolic events after SARS-CoV-2 vaccinations are still raising concerns, predominantly in non-scientific population. The aim of our study was to investigate the differences between haemostasis and inflammatory markers in the subjects vaccinated with mRNA BNT162b2 and vector Ad26.CoV2.S vaccine. MATERIALS AND METHODS: The study included 87 subjects vaccinated with mRNA BNT162b2 and 84 with Ad26.CoV2.S vaccine. All the laboratory parameters (TAT, F 1 + 2, IL-6, CRP, big endothelin-1, platelets, fibrinogen, D-dimers, VWF activity) were investigated for the mRNA vaccine at five (before the first dose, 7 and 14 days after the first and second vaccine dose), and three time points (before the first dose, 7 and 14 days after) for the vector vaccine, respectively. All the markers were measured by well-established laboratory methods. RESULTS: Our results have shown statistically higher CRP levels in the vector group 7 days after vaccination (P = 0.014). Furthermore, study has revealed statistically significant rise in D-dimers (P = 0.004) between tested time points in both vaccine groups but without clinical repercussions. CONCLUSION: Although statistically significant changes in haemostasis markers have been obtained, they remained clinically irrelevant. Thus, our study implicates that there is no plausible scientific evidence of a significant disruption in the coagulation and inflammatory processes after vaccination with BNT162b2 mRNA and Ad26.CoV2.S vector SARS-CoV-2 vaccines.

EFFICACY AND SAFETY OF IMMUNOCHEMOTHERAPY IN TREATMENT OF FOLLICULAR NONHODGKIN'S LYMPHOMA DURING COVID-19 PANDEMIC: A STUDY OF KROHEM, THE CROATIAN COOPERATIVE GROUP FOR HEMATOLOGIC DISEASES

Background: Follicular lymphoma (FL) is a systemic neoplasm of the lymphoid tissue arising from B cell proliferation. The novel monoclonal anti-CD20 antibody obinutuzumab in combination with chemotherapy has been widely accepted as the first choice in front line treatment of FL. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19) is causing increased mortality among patients with lymphoproliferative disorders compared with the general population. Furthermore, there are some concerns in terms of morbidity and mortality for patients with FL because of their immunocompromised status induced by recent exposure to cytotoxic chemotherapy, especially bendamustine and anti-CD20. Aims: To investigate efficacy and safety of immunochemotherapy protocols for patients with newly diagnosed FL during COVID-19 pandemic. Methods: We retrospectively investigated medical data of all patients with newly diagnosed FL grade 1, 2 or 3A from Croatian hematologic registry in period from April 2019 to March 2021. Only patients which required systemic treatment were included in the analysis. All patients received obinutuzumab (G) in combination with either CHOP, bendamustine (B) or CVP chemotherapy protocol. Treatment response was evaluated using international lymphoma response criteria. Results: We analyzed a total of 114 FL patients treated with G-chemotherapy. Mean age was 62.4 ±10.5 years. Majority of patients were female (71/114 (62.3%)). FL grade I was present in 45/114 (39.5%), grade II in 28/114 (24.6%), grade III in 27/114 (23.7%) and not specified (but not IIIB) in 14/114 (12.3%) patients. A total of 61/114 (53.5%) patients were treated with G-B, 49/114 (43%) with G-CHOP and 4/114 (3.5%) with G-CVP immunochemotherapy. Similar rates of adverse events were observed in patients treated with G-CHOP and G-B Median follow up was 17 months. Overall response rate was 94%, complete remission (CR) in 68% and partial remission (PR) in 25% of patients. Median overall survival (OS) and progression free survival (PFS) were not reached with 12-months rates of 94% and 92%, respectively. Patients treated with G-CHOP had statistically significantly superior OS and PFS compared to patients treated with G-B (P=0.002 and P=0.006, respectively, Fig. 1). More favorable survival course associated with G-CHOP in comparison to G-B persisted in multivariate analysis (P=0,026, HR=15,12) after adjustment for age, sex, FLIPI grade and SARS-CoV-2 infection. Total of 12 patients died during the follow up and COVID-19 was cause of death in 5 patients. During the follow-up SARS-CoV-2 infection was diagnosed in 20/114 (17,5%) patients with overall mortality rate of 25%. All of the 7 patients treated with GCHOP recovered from SARS-CoV-2 infection and mortality rate in infected group of patients treated with G-B was 33% (4/12 patients). Image: Summary/Conclusion: Increased COVID-19 mortality in patients with lymphoproliferative disorders was observed in this study. Our group of patients had reduced OS and PFS compared to the GALLIUM trial and SARS-CoV-2 infection was the most pronounced risk factor for death. Even though in some studies bendamustine has shown to be less toxic and more effective than CHOP in FL, there are some important pandemic aspects that must be considered. Bendamustine exposure seems to be associated with worse outcome in case of the infection with SARS-CoV-2. These intriguing differences could play important role in treatment approach in COVID-19 pandemic. Future studies investigating hematological malignancies in COVID-19 pandemic are warranted.