Patients with Multiple Myeloma and Waldenström Macroglobulinemia Have Impaired COVID-19 Vaccine Responsiveness

According to a poster presented at the 2021 ASH Annual Meeting by Andrew R. Branagan, MD, PhD, and colleagues, patients with myeloma and Waldenström macroglobulinemia show impaired functional humoral responses following COVID-19 vaccines. Dr. Branagan, from the Center for Multiple Myeloma at Massachusetts General Hospital Cancer Center in Boston, and researchers noted that patients with Waldenström macroglobulinemia, in particular, have more severe impairment of COVID-19 spike protein (S) antibody (Ab) responses.

Multiple myeloma and Waldenström macroglobulinemia are two malignancies associated with significant immunoparesis, making patients with these conditions susceptible to adverse consequences of COVID-19 infection. However, it is unclear whether these patient populations can mount a sufficient response to COVID-19 vaccines.

To help answer this question, researchers evaluated S antibody levels and T-cell responses in patients with multiple myeloma and Waldenström macroglobulinemia who were vaccinated with one of the three available COVID-19 vaccines in a prospective clinical trial.

The primary endpoint was S Ab levels at 28 days after final vaccination, and secondary endpoints included functional serologic assessments and T-cell responses at 28 days, 6 months, 9 months, and 12 months following vaccination. An S Ab level of 0.80 U/mL was defined as positive and titers >250 U/mL were considered stronger correlates of neutralization.

As of the study presentation, 137 patients (91 with multiple myeloma and 46 with Waldenström macroglobulinemia) had an S Ab assessment available. Median Ab titers were 178.0 (interquartile range [IQR] = 16.10-1,166.0) for multiple myeloma and 3.92 for Waldenström macroglobulinemia (IQR = 0-278.9). Eighty-three patients with multiple myeloma (91%) achieved an S Ab response, while 27 patients with Waldenström macroglobulinemia (56%) had a response.

However, the rate of patients achieving S Ab >250 U/mL were 47.3% (43/91) in the myeloma group and 26.1% (12/46) in the Waldenström macroglobulinemia group. Vaccine-specific S Ab responses >250 u/mL differed with the three vaccine products, and for multiple myeloma and Waldenström macroglobulinemia:

  • Moderna: 67.6% (23/34; p < 0.05) for myeloma and 50.0% (8/16; p < 0.05) for Waldenström macroglobulinemia
  • Pfizer: 38.3% (18/47; p = not significant) and 14.8% (4/27; p < 0.05) for Waldenström macroglobulinemia
  • Johnson & Johnson: 20% (2/10; p= not significant) and 0% (0/3; p = not significant) for Waldenström macroglobulinemia

Multiple myeloma patients who underwent autologous stem cell transplant within 12 months of vaccination demonstrated 100% (5/5; p < 0.05) S Ab responses, however, only 38.9% (14/36) of those actively receiving an anti-CD38 monoclonal antibody and 50.9% (28/55) of those receiving an immunomodulatory drug, had S Ab response.

As evidenced by functional Ab studies performed on 14 patients with myeloma, 14 with Waldenström macroglobulinemia, and 14 healthy donors, the patients with B-cell malignancies showed increased IgA and IgM S Ab production as well as increased FcgR2A binding following a second vaccine, compared with the healthy controls. 

Overall, patients with Waldenström macroglobulinemia showed more severe impairment of COVID-19 S Ab responses. “Most previously untreated Waldenström macroglobulinemia patients achieved S Ab responses, however the most significant reduction in S Ab responses were seen in Waldenström macroglobulinemia patients who received rituximab within 12 months or active BTK inhibitors,” the authors reported. For patients with multiple myeloma, however, disease in remission was associated with improved S Ab response. “Further understanding of the immunological response to COVID-19 vaccination is needed to clarify patients risks, and necessity for booster or alternative protective measures against COVID-19,” they concluded.