The humoral response of mRNA COVID-19 vaccine in hematological diseases: The HEMVACO study

Abstract

Objectives: The HEMVACO study evaluated the humoral response after mRNA anti-SARS-CoV-2 vaccination in an hematological cohort.

Methods: HEMVACO was a prospective, multicentric study registered in ClinicalTrials.gov, number NCT04852796. Patients received two or three doses of BNT162b2 vaccine or mRNA-1273 vaccine. The SARS-CoV-2 TrimericS IgG titers were measured 1, 3, 6 and 12 months after the second dose.

Results: Only 16 patients (11.6%) were naive of hematological treatment and 77 patients (55.8%) were on active treatment for hemopathy. Among the 138 analyzed patients, positive antibody titer at 1 month was obtained in 68.1% of patients with mean serology at 850±883 BAU/ml. Risk factors for vaccine failure were anti-CD20 therapy (OR=111[14.3-873]; P<0.001), hypogammaglobulinemia under 8g/L (OR=2.49[1.05-5.92]; P=0.032) and lymphopenia under 1.5G/L (OR=2.47[1.18-5.17]; P=0.015). Anti-CD20 therapy induced no anti-SARS-CoV-2 seroconversion (96%). Seventy-eight patients (56.5%) received a third dose and could reach the SARS-CoV-2 TrimericS IgG titer of high-risk patients (P=0.54). The median titer at 379 BAU/ml distinguished two groups of vaccine response (99±121 BAU/ml versus 1,109±678 BAU/ml).

Conclusion: Vaccination should be performed before anti-CD20 therapy if the hemopathy treatment can be delayed. Administration of the third vaccine dose was interesting for patients with suboptimal response, defined by a 379 BAU/ml titer in our study.

Keywords: Anti-CD20 monoclonal antibody; Booster immunization; Hematologic diseases; Hypogammaglobulinemia; SARS-CoV-2 vaccine.

Fig. 1

Distribution of anti-Trimeric Spike protein (mean) titers at 1 month, according to the risk factors for severe COVID-19 disease. Very high risk patients were represented by auto or allogeneic stem cell transplant, lymphoid hemopathy (lymphoma, myeloma), in particular treated by anti-CD20 antibody, Burton tyrosine inhibitors or CAR-T cells, and primary immunodeficiency diseases. High-risk patients were represented by other hematological diseases or non-immunosuppressive therapy.

Fig. 2

Anti-Trimeric Spike protein (mean) titers evolution. Very high-risk patients received three doses of mRNA COVID-19 vaccine (auto or allogeneic stem cell transplant, lymphoid hemopathy [lymphoma, myeloma], in particular treated by anti-CD20 antibody, Burton tyrosine inhibitors or CAR-T cells, and primary immunodeficiency diseases). The mean (± SD) anti-Trimeric Spike protein were 371 (± 641), 249 (±493) and 557 (±776) BAU/mL at 1, 3 and 6 months respectively, for 77, 50 and 40 patients, respectively. High-risk patients received two doses of mRNA COVID-19 vaccine and were represented by other hematological diseases or non-immunosuppressive therapy. The mean (± SD) anti-Trimeric Spike protein were 1,504 (±756), 1,056 (±784) and 689 (±778) BAU/mL at 1, 3 and 6 months respectively, for 61, 59 and 18 patients, respectively.