Vaccination for SARS-CoV-2 in Hematological Patients

Abstract

Patients with specific hematological malignancies (HM) are at increased risk for severe disease and death from infection with SARS-CoV-2. In healthy subjects, vaccination against SARS-CoV-2 has been demonstrated to be highly effective in disease prevention, however immunocompromised patients were largely excluded from vaccine randomized controlled trials. In this review, we overview available non-randomized studies addressing effectiveness and safety of several COVID-19 vaccines in patients with HM. Overall, COVID-19 vaccines are safe in patients with HM, with adverse events similar to those in the general population. Though serology testing is not recommended as a test to evaluate vaccine effectiveness, a correlation between higher antibody levels and protection against infection has been reported. Studies evaluating humoral response to COVID-19 vaccine in HM patients demonstrate low immunogenicity, mainly in patients with lymphoproliferative disorders, as well as with certain drugs, including mainly anti-CD20 antibodies, Bruton tyrosine kinase inhibitors, and also roxulitinib ruxolitinib and venetoclax. Seropositivity rates of patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia following mRNA vaccination reach 40-50%. T-cell responses to vaccination are also impaired among these patients. Better humoral response rates are reported in multiple myeloma patients and hematopoietic stem cell transplant, reaching ~75-80%, but not in patients following chimeric antigen receptor T-cell therapy. Patients with chronic myeloid leukemia and myeloproliferative diseases have high response rate to vaccination. Third mRNA vaccine dose is currently recommended to all HM patients. Alternative approaches for vaccination and prevention in patients unable to mount an immune response following full vaccination are provided in the review.

Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario

“…Overall, only 55% of our patients were observed with a successful seroconversion after a prime-boost vaccination (third COVID-19 vaccine). Such a low response rate is consistent with the observation of impaired humoral responses to both non-COVID-19 anti-infective vaccinations [ 39 , 40 , 41 ] and mRNA-based COVID-19 booster vaccines [ 29 , 31 , 42 , 43 , 44 ] in patients with hematologic neoplasms. In a small proportion of analyzed patients with myeloid neoplasms, the seroconversion rate was higher compared to those with lymphoid ones (78% vs. 54%, accordingly).…”

The unique presentation of SARS-CoV-2 Infection in patients with B-cell depletion: definition of ‘persistent inflammatory sero-negative COVID’

“…[ 1 , 2 ] The protracted course reported among B cell depleted patients includes prolonged/intermittent systemic and/or respiratory symptoms, along with persistent respiratory viral shedding, as well as absence of seroconversion. [ 4 , 5 ] Waxing and waning of symptoms occurs over several weeks from diagnosis, with one study reporting median duration of symptoms of 62 days with a maximum of 300 days. Persistence of PCR positivity and infection during the first 12 months following anti-CD20 therapy have been reported to be associated with mortality.…”

“…Hence, persistent viral shedding and seronegativity are insufficient to explain this condition. [ 4 , 7 ] There is growing evidence that these patients have an abnormal/dysregulated T cell response [ 8 , 9 ]. This abnormal T cell function leads to a hyper inflammatory response which does not lead to eradication of the virus.…”

Hematological Aspects of COVID-19

“…Immunogenicity in response to SARS-CoV-2 vaccines is descried in details by Riccardo et al [5]. As opposed to the general population, with almost 100% humoral response to mRNA vaccines, several groups of hematological patients are less likely to develop immunogenicity to these vaccines.…”

“…Those who were treated during the last year with anti-CD-20 agents have even lower seroconversion rates, i.e., up to 10%. Other groups with low response rates are described and include patients following chimeric antigen receptor T-cell infusion, multiple myeloma patients treated with daratumumab and hematopoietic stem cell transplant recipients during the first year after transplant [5].…”