BNT162b2 COVID-19 vaccine is significantly less effective in patients with hematologic malignancies

Abstract

Patients with hematologic malignancies have an increased risk of severe COVID-19 infection. Vaccination against COVID-19 is especially important in these patients, but whether they develop an immune response following vaccination is unknown. We studied serologic responses to the BNT162b2 vaccine in this population. A lower proportion of patients were seropositive following vaccination (75%) than in a comparison group (99%; p < 0.001), and median (interquartile range [IQR]) antibody titers in patients were lower (90 [12.4-185.5] and 173 [133-232] AU/ml, respectively; p < 0.001). Older age, higher lactate dehydrogenase, and number of treatment lines correlated with lower seropositivity likelihood and antibody titers, while absolute lymphocyte count, globulin level, and time from last treatment to vaccination correlated with higher seropositivity likelihood and antibody titers. Chronic lymphocytic leukemia patients had the lowest seropositivity rate followed by indolent lymphoma. Patients recently treated with chemo-immunotherapy, anti-CD20 antibodies, BCL2, BTK or JAK2 inhibitors had significantly less seropositive responses and lower median (IQR) antibody titers (29%, 1.9 [1.9-12] AU/ml; 0%, 1.9 [1.9-1.9] AU/ml; 25%, 1.9 [1.9-25] AU/ml; 40%, 1.9 [1.9-92.8] AU/ml; and 42%, 10.9 [5.7-66.4] AU/ml, respectively; p < 0.001). Serological response to BNT162b2 vaccine in patients with hematologic malignancies is considerably impaired, and they could remain at risk for severe COVID-19 infection and death.

FIGURE 1

Serologic results according to hematologic diagnosis and laboratory results. (A) Seropositivity rates (%) in hematologic malignancy‐specific diagnosis and the comparator group. (B) Post‐vaccination antibody titers in hematologic malignancy‐specific diagnosis and the comparator group. (C) Seropositive patients had a significantly higher globulin level (upper panel), lower lactate dehydrogenase (LDH, middle panel), and higher absolute lymphocyte count (lower panel). HL, Hodgkin lymphoma; MDS, myelodysplastic syndrome; CML, chronic myeloid leukemia; MPN, myeloproliferative neoplasms; AL, acute leukemia; MM, multiple myeloma; A‐NHL, aggressive non‐Hodgkin lymphoma; I‐ NHL, indolent non‐Hodgkin lymphoma; CLL, chronic lymphocytic leukemia

FIGURE 2

Classification tree for seronegativity using current treatment, age, and diagnosis. The first division for discriminating patients is based on current treatment. The second division is based on age >82 years or ≤82 years. The third division for patients aged ≤82 years is based on diagnosis. MoAb, monoclonal antibodies; PIs, proteasome inhibitors; IMIDs, immune modulatory drugs; TKI, tyrosine kinase inhibitors; CIT, chemo‐immunotherapy; BCL2, B‐cell lymphoma 2; JAK2, janus kinase 2; BTK, bruton tyrosine kinase; MM, multiple myeloma; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasms; CML, chronic myeloid leukemia; CLL, chronic lymphocytic leukemia; NHL, non‐Hodgkin lymphoma [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Classification tree for seronegativity using current treatment, absolute lymphocyte count and treatment in the past 60 months. The first division for discriminating patients is based on current treatment. The second division is based on the absolute lymphocyte count. The third division for patients with a lymphocyte count ≤0.885 is based on treatment given in the previous 60 months. MoAb, monoclonal antibodies; PIs, proteasome inhibitors; IMIDs, immune modulatory drugs; TKI, tyrosine kinase inhibitors; CIT, chemo‐immunotherapy; BCL2, B‐cell lymphoma 2; JAK2, janus kinase 2; BTK, bruton tyrosine kinase [Color figure can be viewed at wileyonlinelibrary.com]