Pb2578: antibody response to sars-cov-2 omicron variant in patients with hematological malignancies after the breakthrough infection wave in chongqing, china: a multi-center, prospective study

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: SARS-CoV-2 Omicron variant is still a fatal threat to immunosuppressed hematological malignancies (HM) patients. The neutralizing antibody response after the current Omicron breakthrough infection in HM patients has not yet been established with large sample analysis. Aims: To explore the neutralizing antibody response of HM patients after Omicron breakthrough infection to deal with the possible second wave of novel variants in the future. Methods: During the China’s Omicron infection wave from November 2022 to January 2023, we conducted a multi-center, prospective clinical study in four university hospitals in Chongqing, China, including 361 HM patients and 100 randomly selected age-matched adults without malignant or immunodeficient comorbidities as control. Serum IgG antibody to Omicron spike receptor-binding domain (S-RBD) 3-6 weeks after the breakthrough infection was detected through ELISA method, and data was statistically to distinguish the differences under distinct clinical characteristics and treatment strategies. Results: In this cohort of 361 HM patients and 100 healthy control, median (range) age were 58 (14-83) years and 56 (22-91) years, respectively. 209 (57.9%) and 55 (55%) were male in HM and control group. Serum anti-S-RBD IgG concentration was (36.2 ± 31.0) ng/ml of HM patients comparable to (49.44 ± 16.81) ng/ml of healthy individuals (P <0.001). The concentration of anti-S-RBD in lymphoma (P <0.001) and CLL (P=0.019) was significantly lower while there was no statistical difference in MM (P=0.427) and myeloid cancer (P=0.341) patients when compared with the control group. In the lymphoma subgroup, the concentration of anti-S-RBD in Hodgkin’s lymphoma, multiple B-cell lymphoma and HIV-related lymphoma was significantly lower than that of the control group (all P<0.005), while T or NK/T lymphoma showed no difference (P=0.223). Compared with patients with active disease, HM patients with CR or PR unexpectedly showed lower antibody concentration (all P<0.005), which may be related to the longer clearance time of SARS-CoV-2 in the former. Previously vaccination did not increase the concentration of anti-S-RBD (all P<0.005), but the antibodies in patients who had been vaccinated with three doses were significantly higher than those who had not been vaccinated or vaccinated with 1-2 doses (all P<0.05). The antibody concentration of patients who had been treated with anti-CD20 monoclonal antibody, BTK inhibitor, Bendamustine, PD1/PD-L1 inhibitor, lenalidomide maintenance treatment and auto-HSCT was significantly lower than that of the control group (all P<0.005), while no significant difference in untreated newly diagnosed patients (P=0.392). (Data were shown in Figure 1) Summary/Conclusion: The concentration of anti-S-RBD in HM patients 3-6 weeks after the recent wave of Omicron variant breakthrough infection in China is significantly lower than that in the general population. Many targeted drugs such as CD20 monoclonal antibody and BTK inhibitor, et al have a significant negative impact on the production of antibodies. These results may help the hematologists cope with the possible pandemic of new variant in the future.Keywords: Multiple myeloma, Lymphoma