Multiple Myeloma Patients Display Weakened Antibody Responses to mRNA COVID Vaccines

A new study reports weakened antibody responses to COVID-19 mRNA vaccines among most patients with multiple myeloma, a common form of bone-marrow cancer associated with an immunocompromised state. The research, scheduled for publication by the journal Leukemia, was carried out at the Institute for Myeloma & Bone Cancer Research (IMBCR) in West Hollywood, California under the direction of James Berenson, MD, its Medical and Scientific Director, in collaboration with Emory infectious diseases fellow Samuel Stampfer, MD.

Patients with smoldering myeloma, not requiring treatment, all achieved a good response to COVID-19 vaccination, whereas less than half of patients with active myeloma requiring treatment did. Specifically, only 45 percent of active patients fully responded to the mRNA vaccines whereas less than a quarter showed a partial response and one-third did not respond to the vaccines above background antibody levels.

Serum samples from 103 multiple myeloma patients were obtained prior to vaccination and 2-3 weeks after administration of the first and second vaccines and compared to a group of age-matched healthy controls. Predictors of reduced antibody responses to the vaccines included: older age, impaired renal function, low lymphocyte counts, reduced uninvolved antibody levels, past first line of treatment, and those not in complete remission. Notably, nearly two-thirds of patients who received the Moderna vaccine responded whereas only approximately a quarter who received the Pfizer vaccine did.

"Based on these data, myeloma patients may need to continue social distancing following COVID-19 vaccination, and postvaccine antibody tests may help guide decisions regarding supplementary vaccination or antibody prophylaxis for this vulnerable population," says Emory infectious diseases researcher Samuel Stampfer, who co-designed the clinical study under the guidance of senior author James Berenson. Dr. Berenson stated: "This study highlights the importance of recognizing the limitations of current vaccination approaches to COVID-19 for immune compromised patients and that new approaches will have to be developed to improve their protection from this dangerous infection. It also suggests that there may be clinically significant differences in the effectiveness of different COVID-19 vaccines for immune compromised patients. Until these advances occur, it means that myeloma patients will need to remain very careful even if they have been vaccinated through wearing their masks and avoiding contact with unvaccinated individuals."

The "correlates of protection," or the threshold of antibodies or other immune cells needed for protection, have not been formally established for COVID-19 vaccination. As an interim estimate, the authors selected levels of antibody against SARS-CoV-2 spike protein of more than 250 International Units/milliliter (mL) as "good" because 94 percent of the controls achieved that level, along with a report that COVID-19 survivors with antibodies above 147 IU/ml did not develop any reinfections within six months. Below 250 IU/ml, but above background (50 IU/mL) was considered to be a partial response. One vaccinated myeloma patient did become infected after direct exposure to other COVID-19 infected individuals, after his anti-spike antibody levels declined from 608 to 126 IU/ml six weeks after his second vaccination.

Senior author Dr. Berenson is the founder and Medical and Scientific Director of the Institute for Myeloma & Bone Cancer Research, West Hollywood, CA which funded the study and tested his clinic patients for COVID-19 antibody responses in the Institute's research laboratory. Dr. Stampfer is now in Rama Amara's lab at Emory Vaccine Center/Yerkes National Primate Research Center and is supported by the National Institute of Allergy and Infectious Diseases (T32AI074492).