Impaired Humoral Responses to COVID-19 Vaccination in Patients with Waldenstrom Macroglobulinemia and Multiple Myeloma

Strategic Insights -

Researchers at the National Cancer Institute Frederick have found that patients with symptomatic monoclonal gammopathies, including Waldenstrom macroglobulinemia and multiple myeloma, have impaired humoral responses to COVID-19 vaccination. The study compared the response to BNT162b2 mRNA vaccinations of patients with these conditions with healthy vaccine recipients and found that patients on active therapy affecting B cell development had significantly lower neutralizing antibody (NAb) response rates and magnitudes, including several patients lacking responses even after a third vaccine dose. In contrast, patients off-therapy showed increased NAb with a broad response range.

Key Takeaways:

  • Patients with symptomatic monoclonal gammopathies, including Waldenstrom macroglobulinemia and multiple myeloma, have impaired humoral responses to COVID-19 vaccination.
  • Patients on active therapy affecting B cell development had significantly lower neutralizing antibody (NAb) response rates and magnitudes compared to healthy vaccine recipients.
  • Patients off-therapy showed increased NAb with a broad response range.
  • Repeat vaccination of patients with multiple myeloma or Waldenstrom's macroglobulinemia is beneficial even under active therapy.
  • ELISA Spike-Receptor Binding Domain (RBD) Ab titers in healthy vaccine recipients and patient cohorts were good predictors of the ability to neutralize not only the original WA1 but also the most divergent Omicron variants BA.4/5.
  • Significantly lower NAb responses to BA.4/5 were found in all patient cohorts on-therapy.
  • The MM and WM cohorts off-therapy showed a higher probability to neutralize BA.4/5 after the third vaccination.

Statistics:

  • 60 patients with multiple myeloma (MM) and 20 patients with Waldenstrom's macroglobulinemia (WM) participated in the study.
  • 37 healthy vaccine recipients were used as a control group.
  • The NAb response rate and magnitude were significantly lower in patients on active therapy affecting B cell development ( p < 0.01).
  • The NAb response rate and magnitude were significantly higher in patients off-therapy ( p < 0.001).
  • The ELISA Spike-Receptor Binding Domain (RBD) Ab titers in healthy vaccine recipients and patient cohorts were good predictors of NAb response (R^2 = 0.85).

Sources:

  • Cancers, 2022,14(5816):5816. (Cancers - http://www.mdpi.com/journal/cancers/)
  • Vaccine Weekly, December 28, 2022; p 1247.