Heterogenous Serological Responses to BNT162b2 mRNA Vaccine in Patients with Haematological Malignancies

Background: Patients with active haematological malignancies (HM) have been excluded from clinical trials evaluating vaccines against SARS-CoV-2. Both HM and their treatments are commonly immunosuppressive and are likely to impact COVID-19 vaccine efficacy. Methods: We performed a study assessing serological response to one and two BNT162b2 vaccine doses in healthy healthcare workers (HCWs) and in patients with HM. Peripheral blood samples were collected at three time points: 0-10 days before the first BNT162b2 vaccine jab, on the day of second jab (around day 21) and 7 to 21 days after the second jab. Abbott Architect SARS-CoV-2 IgG Quant II assay was used to quantify serum anti-SARS-CoV-2-S1 IgG antibody (anti-S1 IgG) levels. HM individuals were stratified into groups by current or most recent treatment, latency since treatment and anti-S1 IgG seroconversion status before the first jab. Results: 653 anti-S1 IgG negative participants with HM (median age 64 years, IQR 53 - 72, 52% female) and 69 healthy HCWs (40 [32 - 53] years, 83% female) were included in the study. 18-60 year-old HM patients had lower median anti-S1 IgG response (median 6810 [IQR 635 - 20574] vs 21394 [14289 - 33322], p<0.0001) after two BNT162b2 vaccine doses than the HCWs of the same age group. Compared to 25 patient untreated HM group (72 [59 - 77] years, 48% female, the median anti-S1 IgG 1083 (140 - 5199) AU/mL), HM patients actively treated with Bruton tyrosine kinase inhibitors (BTKi) (median 0 [0 - 3] AU/mL, p<0.0001), ruxolitinib (15 [0 - 45] AU/mL, p =0.0007) or having received anti-CD20 therapy less than 6 months ago (0 [0 - 4], p=0.0011) mounted poor anti-S1 IgG responses to two BNT162b2 vaccine doses. In contrast, patients who received autologous (autoSCT) (6208 [1454 - 17673] AU/mL) or allogeneic hematopoietic stem cell transplant (alloSCT) (6304 [1005 – 17201] AU/mL) and patients treated with tyrosine kinase inhibitors (TKIs) (7320 [1812 - 13691] AU/mL) were among the best serological responders. The latency of 6 months or more between the autoSCT, alloSCT, anti-CD20 therapy or other systemic therapy and vaccination resulted in improved antibody responses. After one dose of BNT162b2, 24 seropositive at baseline HM patients (median age 58 [42 – 63] years 50.0% female) achieved similar anti-S1 IgG levels to those seen in healthy HCWs after two jabs (17896 [4985 - 39860] vs 21394 [14289 - 33322] AU/mL, p=0.23). Anti-S1 IgG levels were meaningfully higher in both baseline seronegative and seropositive HM patients after the second BNT162b2 vaccine jab. Conclusion: Patients with HM mount blunted and heterogeneous antibody responses to full course of BNT162b2 mRNA vaccination. Patients actively treated with BTKi, ruxolitinib and anti-CD20 therapies appear to be the most negatively affected and may be left unprotected from COVID-19 infection. Regardless of seroconversion status before vaccination, many HM patients improve their serologic responses after the second BNT162b2 jab at 3 weeks. Funding Statement: This research is funded by the sponsor of our study - Vilnius University Hospital Santaros Klinikos. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study was approved by the Vilnius Regional Bioethics Committee (approval No. 2021/3-1331-803).