Highly variable SARS-CoV-2 spike antibody responses to two doses of COVID-19 RNA vaccination in patients with multiple myeloma

Oekelen, Oliver Van; Gleason, Charles; Agte, Sarita; Srivastava, Komal; Beach, Katherine F.; Aleman, Adolfo; Kappes, Katerina; Mouhieddine, Tarek H.; Wang, Bo; Chari, Ajai; Cordon‐Cardo, Carlos; Krammer, Florian; Jagannath, Sundar; Simon, Viviana; Wajnberg, Ania; Parekh, Samir

doi:10.1016/j.ccell.2021.06.014

Cited by 191 publications

(242 citation statements)

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“…For second dose-response rates, mRNA vaccines BNT162b2 and mRNA-1273 were assessed in 13 studies [ 16 , 17 , [20] , [21] , [22] , 26 , 27 , 29 , [31] , [32] , [33] , [34] , [35] ] and in four studies [ 16 , 32 , 33 , 35 ], respectively. Within these studies, 17 cancer patient cohorts were identified (11 of which were patients with hematological malignancies, where two were subclassified with chronic lymphocytic leukemia [CLL], three with MM patients, and one with MPN patients; and six cohorts with solid tumors).…”

Section: Resultsmentioning

confidence: 99%

“…Monoclonal antibody therapy [ 16 ] o Anti-CD20 (rituximab) therapy [ 22 , 25 , 30 , 31 , 33 ] o Anti-CD38 (daratumumab) therapy [ 29 , 35 ] …”

Section: Resultsmentioning

confidence: 99%

“…This is due to a reduction in normal plasma cells following anti-CD38 treatment which leads to a decrease in polyclonal immunoglobulin levels essential for humoral immunity. In the study by Van Oekelen et al [ 35 ], anti-CD38 treatment in MM patients was associated with non-seroconversion after two doses of the BNT162b2/mRNA-1273 vaccines based on multivariate analysis with corrections (OR: 4.258; p =0.005). Pimpinelli et al [ 29 ] identified active anti-CD38-based therapy in MM patients with reduced response (50%; p =0.003) compared to anti-CD38-naïve MM patients (93%) following inoculation with the BNT162b2 vaccine.…”

Section: Clinical Factors Associated With Serological Response To Covid-19 Vaccination In Cancer Patientsmentioning

confidence: 99%

“…B-cell maturation antigen (BCMA)-targeted therapy is an emerging treatment modality for MM by targeting the overexpression and hyperactivation of BCMA in B-cells of MM patients [ 65 ]. Poor antibody response to completed two-dose series of the BNT162b2/mRNA-1273 vaccines in MM patients was significantly correlated with BCMA-targeted therapy ( p <0.001) in the study by Van Oekelen et al [ 35 ]. Despite this, little is known about the immunosuppressive properties of BCMA-targeted therapies.…”

Section: Clinical Factors Associated With Serological Response To Covid-19 Vaccination In Cancer Patientsmentioning

confidence: 99%

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Evaluation of COVID-19 vaccine response in patients with cancer: An interim analysis

Tran

Truong

Narendran

2021

European Journal of Cancer

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Background Efficacy and safety data of COVID-19 vaccines among cancer populations have been limited; however, preliminary data from recent studies have emerged regarding their immunogenicity and safety in this population. In this review, we examined current peer-reviewed publications containing serological and safety data following COVID-19 vaccination of patients with cancer. Methods This analysis examined 21 studies with a total of 5,012 cancer patients, of which 2,676 (53%) had hematological malignancies, 2,309 (46%) had solid cancers, and 739 were healthy controls. Serological responses by anti-SARS-CoV-2 spike protein S1/S2 IgG (anti-S IgG) antibody levels and post-vaccination patient questionnaires regarding vaccine-related side effects following the first and second dose were collected and analyzed. Results In general, a single dose of COVID-19 vaccine yields weaker and heterogeneous serological responses in both patients with hematological and solid malignancies. Upon receiving a second dose, serological response rates indicate a substantial increase in seropositivity to the SARS-CoV-2 spike protein in all cancer cohorts, but antibody titers remain reduced in comparison to healthy controls. Furthermore, seroconversion in patients with hematological malignancies was significantly lower compared to patients with solid tumors. COVID-19 vaccines are safe and well-tolerated in cancer patients based on current data of local and systemic effects. Conclusion Together, these data support the prioritization of patients with cancer to receive their first and second doses to minimize the risk of COVID-19 infection and severe complications in this vulnerable population. Additional prophylactic measures must be considered for high-risk patients where current vaccination programs may not mount sufficient protection against SARS-CoV-2 infection.

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Section: Resultsmentioning

confidence: 99%

“…Monoclonal antibody therapy [ 16 ] o Anti-CD20 (rituximab) therapy [ 22 , 25 , 30 , 31 , 33 ] o Anti-CD38 (daratumumab) therapy [ 29 , 35 ] …”

Section: Resultsmentioning

confidence: 99%

Section: Clinical Factors Associated With Serological Response To Covid-19 Vaccination In Cancer Patientsmentioning

confidence: 99%

Section: Clinical Factors Associated With Serological Response To Covid-19 Vaccination In Cancer Patientsmentioning

confidence: 99%

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Evaluation of COVID-19 vaccine response in patients with cancer: An interim analysis

Tran

Truong

Narendran

2021

European Journal of Cancer

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“…Although vaccines have been available since early 2021, achieving near universal coverage has in adults has been an immense logistical challenge, in particular for populous nations where B.1.617.2 is growing rapidly with considerable morbidity and mortality 11 . Current vaccines were designed to target the B.1, Wuhan-1 virus, and the emergence of variants with reduced susceptibility to vaccines such as B.1.351 and P.1 has raised fears for longer term control and protection through vaccination 12,13 , particularly in risk groups 14,15 . The specific reasons behind the explosive global growth of B.1.617.2 in populations remain unclear.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

Mlčochová¹,

Kemp²,

Dhar³

et al. 2021

Preprint

106

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The B.1.617 variant emerged in the Indian state of Maharashtra in late 2020 and has spread throughout India and to at least 40 countries. There have been fears that two key mutations seen in the receptor binding domain L452R and E484Q would have additive effects on evasion of neutralising antibodies. Here we delineate the phylogenetics of B.1.617 and spike mutation frequencies, in the context of others bearing L452R. The defining mutations in B.1.617.1 spike are L452R and E484Q in the RBD that interacts with ACE2 and is the target of neutralising antibodies. All B.1.617 viruses have the P681R mutation in the polybasic cleavage site region in spike. We report that B.1.617.1 spike bearing L452R, E484Q and P681R mediates entry into cells with slightly reduced efficiency compared to Wuhan-1. This spike confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies that is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. Furthermore we show that the P681R mutation significantly augments syncytium formation upon the B.1.617.1 spike protein, potentially contributing to increased pathogenesis observed in hamsters and infection growth rates observed in humans.

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Risks of SARS-CoV-2 Breakthrough Infection and Hospitalization in Fully Vaccinated Patients With Multiple Myeloma

Wang

Berger

2021

JAMA Netw Open

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Highly variable SARS-CoV-2 spike antibody responses to two doses of COVID-19 RNA vaccination in patients with multiple myeloma

Cited by 191 publications

References 10 publications

Evaluation of COVID-19 vaccine response in patients with cancer: An interim analysis

Evaluation of COVID-19 vaccine response in patients with cancer: An interim analysis

SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

Risks of SARS-CoV-2 Breakthrough Infection and Hospitalization in Fully Vaccinated Patients With Multiple Myeloma

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