Anti-CD38 therapy impairs SARS-CoV-2 vaccine response against alpha and delta variants in patients with multiple myeloma

Henriquez, Soledad; Zerbit, Jérémie; Bruel, Timothée; Ouedrani, Amani; Planas, Delphine; Deschamps, P; Staropoli, Isabelle; Hadjadj, Jérôme; Varet, Bruno; Ermak, Natalia; Bouscary, Didier; Willems, Lise; Fouquet, Guillemette; Decroocq, Justine; Franchi, Patricia; Deau, Bénédicte; Terrier, Benjamin; Tamburini, Jérôme; Chatenoud, Lucienne; Schwartz, Olivier; Vignon, Marguerite

doi:10.1182/blood.2021013714

Cited by 29 publications

(27 citation statements)

References 13 publications

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“…Patients with multiple myeloma (MM) are at increased risk of infection and severe outcomes from COVID-19 infection, 1,2 partly owing to inadequate protection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. [2][3][4][5][6][7] Their susceptibility stems from both immune-suppressive treatments used for MM and underlying immune-deficiency from the disease itself. 4,6,8 However, it is unknown how much risk is shared by patients with monoclonal gammopathy of undetermined significance (MGUS), 9,10 a precursor state to MM that does not require immune-suppressive treatment but may be associated with immune-deficiency.…”

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confidence: 99%

“…[2][3][4][5][6][7] Their susceptibility stems from both immune-suppressive treatments used for MM and underlying immune-deficiency from the disease itself. 4,6,8 However, it is unknown how much risk is shared by patients with monoclonal gammopathy of undetermined significance (MGUS), 9,10 a precursor state to MM that does not require immune-suppressive treatment but may be associated with immune-deficiency. Here, we measured the risk of breakthrough infections among vaccinated patients with MM or MGUS relative to the patients without MM or MGUS in the national Veterans Affairs (VA) health care system and described the association of MM-specific treatments with breakthrough risk.…”

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confidence: 99%

“…Prior studies have shown decreased vaccine response in patients on anti-CD38-directed therapies and chemotherapy. 4,7 However, the effect of less immunosuppressive therapies, such as proteasome inhibitors, on vaccine response is unknown. 6 To evaluate impact on breakthrough infection risk, we categorized type of systemic anti-MM treatments received and timing of last therapy before vaccination.…”

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confidence: 99%

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Increased COVID-19 breakthrough infection risk in patients with plasma cell disorders

Branch‐Elliman

et al. 2022

Blood

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Increased COVID-19 breakthrough infection risk in patients with plasma cell disorders

Branch‐Elliman

et al. 2022

Blood

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Section: Introductionmentioning

confidence: 99%

“…9,10 However, very few data are actually available about the cellular response to SARS-CoV-2 mRNA vaccination 11 and the efficacy of the mRNA vaccine, including the booster dose, to the different SARS-CoV-2 variant characterized by mutations encoding for the spike protein. 12 Since November 2021, the B.1.1.529 (Omicron) variant has rapidly become dominant globally. 13 Omicron partially evades antibodies induced by infection or vaccination and it raises concerns regarding the effectiveness of current vaccines.…”

Section: Introductionmentioning

confidence: 99%

Impact of Omicron variant on the response to SARS-CoV-2 mRNA Vaccination in multiple myeloma

Storti

Marchica

Vescovini

et al. 2022

Preprint

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Multiple myeloma (MM) patients may have a reduced response to vaccination due to immunodeficiency. The humoral and cellular response to SARS-CoV-2 mRNA full vaccination and booster dose as well as the impact of spike variants, including the emerging Omicron one, are still unclear and have been investigated in this study in a cohort of MM patients and those with pre-malignant monoclonal gammopathies. Firstly, we have shown that MM patients with relapsed-refractory disease (MMR) had a reduced spike-specific antibody levels and neutralizing titers after SARS-CoV-2 mRNA full vaccination. Interestingly, all the analyzed variants, remarkably Omicron, had a significant negative impact on the neutralizing ability of the vaccine-induced antibodies in all patients with MM and in smoldering MM too. Moreover, lower spike-specific IL-2-producing CD4+ T cells and reduced cytotoxic spike-specific IFN-γ and TNF-α-producing-CD8+ T cells were found in MM patients as compared to MGUS. Finally, we found that booster immunization improved SARS-CoV-2 spike humoral and cellular responses in newly diagnosed MM (MMD) patients and in most, but not all, MMR patients. After the booster dose, a significant increase of the neutralizing antibody titers against almost all the analyzed variants was achieved in MMD. On the other hand, in MMR patients, Omicron retain a negative impact on neutralizing ability, suggesting these patients need to be considered still at risk of Omicron SARS-CoV-2 infection with a clinically relevant disease.

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Survival in multiple myeloma and SARS‐COV‐2 infection through the COVID‐19 pandemic: Results from the EPICOVIDEHA registry

Musto,

Salmanton‐García,

Sgherza

et al. 2023

Hematological Oncology

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Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) infection and subsequent coronavirus (20)19 disease (COVID‐19)‐related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID‐19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS‐CoV‐2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow‐up was 52 days for the entire cohort and 83 days for survivors. Three‐hundred and three patients died (24%) and COVID‐19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109/L was found to be protective. This data suggests that MM patients remain at risk of SARS‐CoV‐2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.

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Anti-CD38 therapy impairs SARS-CoV-2 vaccine response against alpha and delta variants in patients with multiple myeloma

Cited by 29 publications

References 13 publications

Increased COVID-19 breakthrough infection risk in patients with plasma cell disorders

Increased COVID-19 breakthrough infection risk in patients with plasma cell disorders

Impact of Omicron variant on the response to SARS-CoV-2 mRNA Vaccination in multiple myeloma

Survival in multiple myeloma and SARS‐COV‐2 infection through the COVID‐19 pandemic: Results from the EPICOVIDEHA registry

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