Definition of factors associated with negative antibody response after COVID-19 vaccination in patients with hematological diseases

Abstract

COVID-19 in patients with hematological diseases is associated with a high mortality. Moreover, preventive vaccination demonstrated reduced efficacy and the knowledge on influencing factors is limited. In this single-center study, antibody levels of the SARS-CoV-2 spike protein were measured ≥ 2 weeks after 2nd COVID-19 vaccination with a concentration ≥ 0.8 U/mL considered positive. Between July and October 2021, in a total of 373 patients (median age 64 years, 44% women) with myeloid neoplasms (n = 214, 57%), lymphoid neoplasms (n = 124, n = 33%), and other diseases (n = 35, 10%), vaccination was performed with BNT162b2 (BioNTech), mRNA-1273 (Moderna), ChADOx1 (AstraZeneca), or a combination. A total of 229 patients (61%) were on active therapy within 3 months prior vaccination and 144 patients (39%) were previously treated or treatment naïve. Vaccination-related antibody response was negative in 56/373 patients (15%): in 39/124 patients with lymphoid neoplasms, 13/214 with myeloid neoplasms, and 4/35 with other diseases. Active treatment per se was not correlated with negative response. However, rituximab and BTK inhibitor treatment were correlated significantly with a negative vaccination response, whereas younger age and chronic myeloid leukemia (CML) disease were associated with positive response. In addition, 5 of 6 patients with myeloproliferative neoplasm (MPN) and negative vaccination response were on active treatment with ruxolitinib. In conclusion, a remarkable percentage of patients with hematological diseases had no response after 2nd COVID-19 vaccination. Multivariable analysis revealed important factors associated with response to vaccination. The results may serve as a guide for better protection and surveillance in this vulnerable patient cohort.

Optimal time for COVID-19 vaccination in rituximab-treated dermatologic patients

“…The negative impact of rituximab on vaccines’ immunogenicity has been demonstrated for many vaccines before the arrival of COVID-19 vaccines ( 27 – 29 ). Despite the differences in dosage and timing of drug administration, most patients who required repeated courses of rituximab treatment, including those with IMDD, have struggled to mount humoral immunity following COVID-19 vaccines ( 8 , 9 , 20 , 30 – 32 ). Attempts to rectify the situation by using more-immunogenic vaccine platforms (e.g., mRNA and viral vector technologies), lowering rituximab dose, or giving additional vaccine doses have not shown promising benefits ( 32 – 36 ).…”

Non-Myelofibrosis Chronic Myeloproliferative Neoplasm Patients Show Better Seroconversion Rates after SARS-CoV-2 Vaccination Compared to Other Hematologic Diseases: A Multicentric Prospective Study of KroHem

“…However, CML patients in major and deep molecular responses seem to regain immunocompetency irrespective of TKI therapy or treatment-free remission [ 22 ]. Adequate disease control typically prevails in current-day CML cohorts, resulting in COVID-19 mortality similar to that of the general population in the same era of the pandemic [ 23 ], consistent reports of high seroconversion rates [ 12 , 14 ], and production of both humoral and cellular response to SARS-CoV-2 vaccines [ 24 ]. In contrast, BCR-ABL-1 negative CMPNs are associated with an increased risk of severe forms of COVID-19, most prominently MF, where case-fatality risk is 48% [ 25 , 26 ].…”

“…Hematologic malignancy is already associated with an attenuated response to other vaccines [ 8 , 9 , 10 ], and those who had received B-cell-depleting therapy had no antibody response with prolonged viral shedding following SARS-CoV-2 infection [ 11 ]. Several single-center studies soon raised concern about suboptimal seroconversion rates following a standard two-dose regimen of SARS-CoV-2 vaccines [ 12 , 13 , 14 , 15 ].…”

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

“…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. …”