Effectiveness, immunogenicity, and safety of COVID-19 vaccines for individuals with hematological malignancies: a systematic review

Abstract

The efficacy of SARS-CoV-2 vaccination in patients with hematological malignancies (HM) appears limited due to disease and treatment-associated immune impairment. We conducted a systematic review of prospective studies published from 10/12/2021 onwards in medical databases to assess clinical efficacy parameters, humoral and cellular immunogenicity and adverse events (AE) following two doses of COVID-19 approved vaccines. In 57 eligible studies reporting 7393 patients, clinical outcomes were rarely reported and rates of SARS-CoV-2 infection (range 0–11.9%), symptomatic disease (0–2.7%), hospital admission (0–2.8%), or death (0–0.5%) were low. Seroconversion rates ranged from 38.1–99.1% across studies with the highest response rate in myeloproliferative diseases and the lowest in patients with chronic lymphocytic leukemia. Patients with B-cell depleting treatment had lower seroconversion rates as compared to other targeted treatments or chemotherapy. The vaccine-induced T-cell response was rarely and heterogeneously reported (26.5–85.9%). Similarly, AEs were rarely reported (0–50.9% ≥1 AE, 0–7.5% ≥1 serious AE). In conclusion, HM patients present impaired humoral and cellular immune response to COVID-19 vaccination with disease and treatment specific response patterns. In light of the ongoing pandemic with the easing of mitigation strategies, new approaches to avert severe infection are urgently needed for this vulnerable patient population that responds poorly to current COVID-19 vaccine regimens.

Prevention and treatment of COVID-19 in patients with benign and malignant blood disorders

“…Perhaps the most notable and consequential adverse reaction is VITT, a rare complication associated with certain adenovirus-vectored SARS-CoV-2 vaccines (addressed elsewhere this collection). In their systematic review and meta-analysis on COVID-19 vaccines in patients with HM, Piechotta et al concluded that reported adverse events were largely consistent with the safety profile observed in the general population [ 6 ]. Adverse events of interest to the Hematology practitioners have been reported that we will briefly discuss here.…”

“…Patients with hematologic malignancies (HM) are a heterogenous group with a large variety of diseases and a broad spectrum of severity affecting the degree of immunosuppression and vulnerability to COVID-19; this is further compounded by the treatment received as well as age and comorbidities [ [3] , [4] , [5] , [6] ]. As a group, those patients are consistently shown to have a high risk of a severe and complicated COVID-19 course with high rates of hospitalization, respiratory failure and death; the risk is particularly elevated in those with B-cell lymphoid malignancies who received lymphocytotoxic therapies.…”

“…As a group, those patients are consistently shown to have a high risk of a severe and complicated COVID-19 course with high rates of hospitalization, respiratory failure and death; the risk is particularly elevated in those with B-cell lymphoid malignancies who received lymphocytotoxic therapies. In addition, the humoral vaccine response in this high risk group is blunted and they are less likely to seroconvert after vaccination, although a relatively robust cellular immunity response to vaccine appears to be preserved; however, the data on cellular immunity is still too scarce to allow generalization [ [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] ]. A systematic review that identified 57 studies reporting on 7393 patients reported heterogenous vaccine-induced seroconversion rates and cellular immunity in HM patients, but the response was in general lower than reported in healthy participants in the same studies, with the lowest immunity rates reported in CLL, and the highest in myeloproliferative disorders [ 6 ].…”

“…In addition, the humoral vaccine response in this high risk group is blunted and they are less likely to seroconvert after vaccination, although a relatively robust cellular immunity response to vaccine appears to be preserved; however, the data on cellular immunity is still too scarce to allow generalization [ [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] ]. A systematic review that identified 57 studies reporting on 7393 patients reported heterogenous vaccine-induced seroconversion rates and cellular immunity in HM patients, but the response was in general lower than reported in healthy participants in the same studies, with the lowest immunity rates reported in CLL, and the highest in myeloproliferative disorders [ 6 ]. A meta-analysis of 64 studies (published through November 4, 2021) comprising 8546 adult patients with HM found a pooled anti-SARS-CoV-2 IgG antibody seroresponse (SR) to SARS-CoV-2 vaccination of 59%, which varied according to malignancy (myeloid having better response than lymphoid malignancies) and treatment history; the response was better in those who received stem cell transplant (SCT) or have not been treated, and poorer in those receiving chimeric antigen receptor T-cell (CAR-T) therapy or recent anti-CD20 therapy.…”

“…Of note, patients with HM who had breakthroughs were older and had more comorbidities than those without breakthroughs, in particular hypertension, diabetes mellitus type 2 and obesity [ 12 ]. Finally, the waning of immunity and the emergence of variants of concerns (VOC), some of which are associated with decreased neutralization effectiveness and unknown effect on cellular immune response, further supports the need for boosting and, possibly, modified formulation, especially in vulnerable groups, but further research is needed to evaluate the effectiveness of those strategies in protecting against infection, illness and death [ 6 ].…”