BackgroundMultiple myeloma (MM) and Waldenström macroglobulinemia (WM) are associated with significant immunoparesis. Based on the ongoing COVID-19 pandemic, there is an urgent need to understand whether patients are able to mount a sufficient response to COVID-19 vaccines.MethodsPatients were vaccinated with BNT162b2 mRNA (Pfizer/BioNTech), mRNA-1273 (Moderna), or JNJ-78436735 (Johnson & Johnson). SARS-CoV-2 spike protein (S) antibodies were detected with the Elecsys assay (Roche Diagnostics). Primary endpoint is S antibody detection 28 days after final vaccination. Secondary endpoints include functional serologic assessments and T-cell responses at 28 days, 6 months, 9 months, and 12 months.Results141 patients have been enrolled to date, 136 (91 MM and 45 WM) of whom had initial S antibody assessment. Median antibody titer was 178.0 (IQR, 16.10-1166.0) for MM and 3.96 (IQR, 0-282.8) for WM. S antibody response rate was 91% (83/91) in MM and 60% (27/45) in WM. However, response rates for achieving S antibody >100 U/mL were 56% (51/91) in MM and 33% (15/45) in WM. Vaccine-specific S antibody responses following mRNA-1273, BNT162b2, and JNJ-78436735 were 74% (25/34; p<0.05), 51% (24/47; p=NS), and 20% (2/10; p<0.05) in MM and 67% (10/15; p<0.005), 19% (5/27; p<0.05), and 0% (0/3; p=NS) in WM. Among MM patients with progressive disease, S antibody response >100 u/mL occurred in 45% (9/20) as opposed to 65% (35/54) for VGPR+ (p100 U/mL occurred in 53% (19/36) and 56% (31/55), respectively (p=NS). Among WM patients, S antibody responses >100 U/mL occurred in 73% (8/11) (p<0.05) previously untreated; 0% (0/8) (p<0.05) received rituximab within 12 months; 15% (3/20) (p<0.05) on an active Bruton Tyrosine Kinase (BTK) inhibitor; and 29% (4/14) (p=NS) received other therapies.ConclusionsThese preliminary data suggest impaired serologic responses following COVID-19 vaccines in patients with both MM and WM. Overall, WM patients showed more severe impairment of COVID-19 S antibody responses. Most previously untreated WM patients achieved S antibody responses, however suboptimal antibody responses were seen in WM patients who received rituximab within 12 months or on active BTK inhibitors. In MM patients, being in disease remission associated with improved S antibody response. Vaccination among MM and WM patients with MRNA-1273 elicited significantly higher S antibody response rates comparison to other vaccines. Complete serologic responses including neutralization and T-cell studies are pending and will be updated. Further understanding of the immunological response to COVID19 vaccination is needed to clarify patients risks, and necessity for booster or alternative protective measures against COVID-19.