Immunogenicity of SARS-CoV-2 vaccines in patients with multiple myeloma: a systematic review and meta-analysis

Abstract

Patients with multiple myeloma (MM) have a diminished immune response to coronavirus disease 2019 (COVID-19) vaccines. Risk factors for an impaired immune response are yet to be determined. We aimed to summarize the COVID-19 vaccine immunogenicity and to identify factors that influence the humoral immune response in patients with MM. Two reviewers independently conducted a literature search in MEDLINE, Embase, ISI Web of Science, Cochrane library, and Clinicaltrials.gov from existence until 24 May 24 2022. (PROSPERO: CRD42021277005). A total of 15 studies were included in the systematic review and 5 were included in the meta-analysis. The average rate (range) of positive functional T-lymphocyte response was 44.2% (34.2%-48.5%) after 2 doses of messenger RNA (mRNA) COVID-19 vaccines. The average antispike antibody response rates (range) were 42.7% (20.8%-88.5%) and 78.2% (55.8%-94.2%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. The average neutralizing antibody response rates (range) were 25% (1 study) and 62.7% (53.3%-68.6%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. Patients with high-risk cytogenetics or receiving anti-CD38 therapy were less likely to have a humoral immune response with pooled odds ratios of 0.36 (95% confidence interval [95% CI], 0.18, 0.69), I2 = 0% and 0.42 (95% CI, 0.22, 0.79), I2 = 14%, respectively. Patients who were not on active MM treatment were more likely to respond with pooled odds ratio of 2.42 (95% CI, 1.10, 5.33), I2 = 7%. Patients with MM had low rates of humoral and cellular immune responses to the mRNA COVID-19 vaccines. Further studies are needed to determine the optimal doses of vaccines and evaluate the use of monoclonal antibodies for pre-exposure prophylaxis in this population.

Use of Oral Antivirals Ritonavir-Nirmatrelvir and Molnupiravir in Patients with Multiple Myeloma Is Associated with Low Rates of Severe COVID-19: A Single-Center, Prospective Study

“…The SARS-CoV-2 pandemic is a major cause of morbidity and mortality worldwide. Patients with MM are at high risk for severe infection, breakthrough infection, and they present suboptimal humoral responses to COVID-19 vaccination [ 16 , 17 , 18 , 19 , 20 ]. Unfortunately, in some patients with cancer, the infection cannot be completely controlled with antiviral drugs and supportive care, and they ultimately develop severe disease and need hospitalization [ 8 ].…”

Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)

“…Several studies have evaluated the immune response following the prime complete COVID-19 vaccination in patients with MM [ 68 , 71 – 110 ]. Three large meta-analyses have summarized the findings of these studies [ 32 , 33 , 111 ]. Gagelmann et al included data on 1564 patients from 13 studies and showed a pooled antibody response of 76% (95% CI: 67–83%) with significant heterogeneity (I² = 91%) [ 33 ].…”

“…A longer time interval of 3 months from the last treatment dose to vaccination may further enhance seroconversion rates [ 112 ]. Patients with high-risk cytogenetics were also less likely to respond to vaccination (pooled OR of two studies 0.36, 95% CI: 0.18–0.69, I 2 = 0%) [ 32 ].…”

“…Studies have shown that the initial two-dose vaccination scheme results in reduced levels of SARS-CoV-2-specific CD4 + T-cells, but not CD8 + T-cells, compared with healthy individuals [ 123 ]. A pooled analysis of three studies has shown that, on average, the rate of positive functional T-lymphocyte response was 44.2% (34.2–48.5%) after two doses of mRNA-based SARS-CoV-2 vaccines [ 32 ]. Following booster vaccination, patients with MM show remarkable CD4 + T cell-mediated cytokine responses against the Wuhan, Delta and Omicron strains [ 113 , 118 – 120 ].…”

Nirmatrelvir/ritonavir for the treatment of immunocompromised adult patients with early‐stage symptomatic COVID‐19: A real‐life experience

“…The increased risk of progression to severe disease implies a further source of concern for patients with some degree of primary or acquired immune deficiency, such as those with hematological malignancies or receiving immunosuppressive therapies 2,3 . The decreased effectiveness of vaccination against SARS‐CoV‐2 in these populations has been consistently reported 4–6 . Therefore, the development of effective therapeutic options for high‐risk immunocompromised patients has become a key priority.…”