Highly variable response to COVID-19 vaccine in multiple myeloma patients

December 2021 Prevention Nalinee Pathak

In a recent research letter published in Cancer Cell, the researchers found that a proportion of multiple myeloma (MM) patients receiving anti-BCMA or anti-CD38 therapies lacked T-cell responses and anti-SARS-CoV-2 Spike (anti-S) antibodies post COVID-19 vaccination.

In this era of coronavirus pandemic affecting the whole world, vaccines have played an instrumental role in preventing hospitalizations and mortality in healthy individuals. However, immunocompromised individuals with malignancies such as MM are at greater risk of COVID-19 related complications. Recent data by the same group showed that patients with MM had a variable anti-S IgG antibody response after receiving two doses of vaccines. Moreover, 15% of these patients completely lacked any antibody response.

The authors wrote in the article “We wanted to determine whether MM patients without detectable anti-S IgG antibodies to SARS-CoV-2 immunization (seronegative) had detectable SARS-CoV-2 B and T cell responses after SARS-CoV-2 vaccination, which would possibly provide some protection against severe disease even in the absence of anti-S antibodies”. “Such data are urgently required to guide masking, social distancing, and passive antibody/booster vaccination strategies for potentially vulnerable MM patients treated with these anti-cancer agents as we enter the second fall season of the COVID-19 pandemic”.

Study

A high-resolution flow cytometry assays involving multiple immune markers was utilized to assess T-cell responses among MM (n=44) and healthy (n=14) individuals. The MM patients included 17 seronegative and 27 seropositive individuals. The participants in the study were profiled at least two weeks before their scheduled second vaccine dose, where all these patients received either Pfizer-BioNTech (n=42), or Moderna (n=14) vaccines.

Result

The spike-protein reactive B cells were detected in 96% of seropositive patients (n=24), whereas only 40% of seronegative patients (n=6) had this response. Additionally, seronegative patients had lower B cells in their peripheral blood as compared to seropositive patients (p <0.0015).  A direct correlation between spike-protein-reactive B cells or absolute B-cell count and anti-S IgG antibody concentration was observed (Spearman R=0.44; p=0.002 and Spearman R=0.51; p=0.00047, respectively). Also. the seronegative patients had reduced total CD4+ T cell counts vs seropositive patients (p=0.0065). The CD4+T cell responses were similar between healthy and seropositive MM individuals, however only six (35%) seronegative MM patients had a CD4+ T-cell response. CD8+ T-cell response were observed in 50% of healthy, 50% seropositive and 28% seronegative MM individuals, respectively. Importantly, few MM patients on anti-BCMA bispecific (33%; n = 2) or anti-CD38 therapies (68%; n = 13) had SARS-CoV-2–specific CD4+ T-cell responses as compared to patients on either anti-myeloma (90%, n=9) or CART-T cell therapy (89%, n=9).

Conclusion

The study on MM patients showed a high degree of variation in SARS-CoV-2-specific B and T cell response. Importantly, lack of anti-S antibodies post vaccination in patients on anti-CD38 and anti-BCMA antibody-based therapies emphasizes the need of serological testing after vaccination in these subgroups of patients. Passive antibody treatment could be a treatment option for such non-responsive group of MM patients.

References

Aleman A, Upadhyaya B, Tuballes K, et al. Variable cellular responses to SARS-CoV-2 in fully vaccinated patients with multiple myeloma. Cancer Cell. Published online October 19, 2021. Accessed October 22, 2021. doi:10.1016/j.ccell.2021.09.015

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