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Blood Adv . Prospective study of immunogenicity to SARS-CoV-2 booster vaccines in multiple myeloma and Waldenström macroglobulinemia

tetano

Editor, Senior Moderator
Blood Adv


. 2025 Jun 5:bloodadvances.2025016513.
doi: 10.1182/bloodadvances.2025016513. Online ahead of print. Prospective study of immunogenicity to SARS-CoV-2 booster vaccines in multiple myeloma and Waldenström macroglobulinemia

Andrew R Branagan[SUP] 1 [/SUP], Clifton C Mo[SUP] 2 [/SUP], Matthew M Lei[SUP] 3 [/SUP], Joshua Gustine[SUP] 4 [/SUP], Andrew J Yee[SUP] 3 [/SUP], Elizabeth O'Donnell[SUP] 5 [/SUP], Jorge J Castillo[SUP] 6 [/SUP], Omar Nadeem[SUP] 6 [/SUP], Catherine Flynn[SUP] 7 [/SUP], Zachary Bernstein[SUP] 8 [/SUP], Rie Nakamoto-Matsubara[SUP] 3 [/SUP], Kirsten E Meid[SUP] 7 [/SUP], Rakesh Verma[SUP] 9 [/SUP], Zachary R Hunter[SUP] 7 [/SUP], Maria Luisa Guerrera[SUP] 7 [/SUP], Galit Alter[SUP] 10 [/SUP], Jill N Burke[SUP] 3 [/SUP], Cynthia C Harrington[SUP] 3 [/SUP], Emerentia A Agyemang[SUP] 1 [/SUP], Marilyn T Gammon[SUP] 3 [/SUP], Kathleen J Lively[SUP] 3 [/SUP], Lisette Packer[SUP] 3 [/SUP], Nora Horick[SUP] 11 [/SUP], Jacob P Laubach[SUP] 6 [/SUP], Constantine S Mitsiades[SUP] 12 [/SUP], Nikhil C Munshi[SUP] 7 [/SUP], Kenneth C Anderson[SUP] 6 [/SUP], Steven P Treon[SUP] 7 [/SUP], Paul G Richardson[SUP] 2 [/SUP], Noopur S Raje[SUP] 1 [/SUP], Shayna Sarosiek[SUP] 7 [/SUP]



Affiliations
Abstract

Patients with multiple myeloma (MM) and Waldenström macroglobulinemia (WM) have increased risk of severe COVID-19. Impaired humoral responses to the primary vaccination series against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in MM and WM patients, but impact of booster vaccinations and functional status of the elicited antibodies is unknown. We performed a prospective cohort study investigating SARS-CoV-2 vaccination in MM (n=93) and WM (n=48) patients. The primary endpoint was effective immune response (EIR) at 28 days after the primary vaccination series (i.e., anti-spike SARS-CoV-2 antibody titer >250 U/mL). The EIR rate after the primary vaccination series was 47% and 25% in MM and WM patients, respectively. Following the first and second booster vaccinations, the EIR rates increased to 84% and 91% in MM patients, respectively, and 60% and 89% in WM patients, respectively. Factors associated with lower EIR in MM patients were hypogammaglobulinemia, lymphopenia, and treatment with anti-CD38 monoclonal antibody or corticosteroid. Treatment with a BTK inhibitor or rituximab was associated with a lower EIR in WM patients, while asymptomatic and treatment naïve WM patients had a higher EIR. Functional profiling identified reduced antibody-dependent cellular phagocytosis (ADCP), neutrophil phagocytosis (ADNP), and NK cell activity (ADNKA) against wild-type and variant SARS-CoV-2 (a, b, and g) in both MM and WM patients compared to healthy donors. Our data demonstrate that although MM and WM patients have impaired humoral responses to the primary SARS-CoV-2 vaccination series, repeated booster vaccines significantly improve immunogenicity. The study was registered at ClinicalTrials.gov (#NCT04830046).


 
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