Seroconversion to mRNA SARS-CoV-2 Vaccines in Hematologic Patients

Abstract

Hematologic patients show lower responses to SARS-CoV-2 vaccines, but predictors of seroconversion are lacking. In this prospective cohort study, hematologic patients undergoing SARS-CoV-2 mRNA vaccination at a single center in Milan, Italy, were sampled for anti-Spike and anti-Nucleocapsid IgG titer at 5 ± 1 weeks and at 3 months from the second vaccine dose. Patients (N = 393) received either BNT162b2 (Pfizer-BioNTech, 48%) or MRNA-1273 (Moderna, 52%), and 284 (72%) seroconverted and 100% persisted at 3 months. Non-response was higher in chronic lymphocytic leukemia (CLL) and lymphoma patients, and in those treated with small molecules and monoclonal antibodies. In myeloid neoplasms, lower responses were detected in patients with acute myeloid leukemia treated with venetoclax plus hypomethylating agents and in patients with myelofibrosis receiving ruxolitinib. Multivariable analysis showed that seroconversion was favorably associated with a diagnosis other than indolent lymphoma/CLL [OR 8.5 (95% CI 4.1–17.6)], lack of B-cell-depleting therapy [OR 3.15 (1.7–5.9)], and IgG levels within the normal range [OR 2.2 (1.2–4.2)]. We developed a simple algorithm according to these 3 risk factors [(A) diagnosis of indolent lymphoma/CLL, (B) B-cell-depleting treatment, and (C) low IgG] to predict non-response. IgG levels and treatment may be modifiable risk factors and should be considered for timing of vaccine administration.

The third dose of mRNA SARS-CoV-2 vaccines enhances the spike-specific antibody and memory B cell response in myelofibrosis patients

“…Patient #583, affected also by chronic lymphocytic leukemia, is in treatment with ibrutinib; patient #552 received a B-celldepleting treatment with anti CD20 monoclonal antibodies for a non-Hodgkin lymphoma some years ago, without IgG recovery before the vaccination, and patient #497, affected by fibromyalgia, is in chronic therapy with methylprednisolone, that induces lymphopenia and hypogammaglobulinemia. As such, in line with other recent reports, the lower response to mRNA vaccines in hematologic patients seems to be influenced by B-cell depleting therapies, hypogammaglobulinemia (42) and immunosuppressive treatment (43), regardless of therapy with ruxolitinib.…”

Vaccinations in hematological patients in the era of target therapies: Lesson learnt from SARS-CoV-2

“…Backbone chemotherapy may also hamper immunity, and lower seroconversion rates were registered after bendamustine. Furthermore, lower absolute lymphocyte count and pre-vaccine hypogammaglobulinemia were associated with reduced humoral response [ 9 , [31] , [32] , [33] , [34] , [35] ] along with vaccination during active disease phase [ 31 ] and the diagnosis of aggressive lymphoma [ 23 , 25 ].…”

“…BCR-ABL tyrosine-kinase inhibitors (TKI) represent the mainstay of care for chronic myeloid leukemia (CML) and may induce off-target B-cell impairment [ 65 ]. However, almost all subjects on treatment with TKI obtained seroconversion to SARS-CoV-2 vaccination in clinical experiences ( Table 3 ) [ 9 , 27 , 66 , 67 ] . Similarly, vaccination against Influenza induced seroconversion in all CML patients investigated, particularly after the second dose.…”

“… Reference Agent Malignancy type Vaccine type Number of patients Seroconversion rate Negative prognostic factors for seroconversion Fiorino F, Biomedicines 2021 [ 71 ] Ruxolitinib MF SARS-CoV2 vaccine 16 68% Guglielmelli P, Am J Hematol 2021 [ 70 ] Ruxolitinib MPN SARS-CoV2 vaccine 18 33% Pimpinelli F, J Hematol Oncol 2021 [ 74 ] Ruxolitinib MPN SARS-CoV2 vaccine 8 62.5% Caocci G, Ann Hematol 2022 [ 73 ] Ruxolitinib MF SARS-CoV2 vaccine 10 60% Ikeda D, Front Med (Lausanne). 2022 [ 72 ] Ruxolitinib MPN SARS-CoV2 vaccine 20 80% Fattizzo B, Front Imm, 2022 [ 9 ] Ruxolitinib MPN SARS-CoV2 vaccine 36 75% Harrington P, Blood Cancer Journal 2022 [ 75 ] Ruxolitinib MPN SARS-CoV2 vaccine 12 50% Haggenburg S, Blood Adv 2022 [ 27 ] Ruxolitinib MPN SARS-CoV2 vaccine 38 49% 1) Older age 2) Low baseline IgG4 serum levels 3) Low baseline NK and B-cells counts Rotterdam J, Ann Hematol 2022 [ 67 ] Ruxolitinib+Fedratinib MPN SARS-CoV2 vaccine 24 16% MPN: Myeloproliferative neoplasms; MF: Myelofibrosis. …”

“…[ 8 ]. In fact, the immune system of many hematological patients is impaired due to the disease itself and the several therapies used [ 8 , 9 ]. The latter include traditional chemotherapy and cytotoxic immunosuppressants as well as novel drugs that enrich the therapeutical landscape of hematologic diseases.…”