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COVID-19 Vaccine Responsiveness in Patients with MM and Waldenström Macroglobulinemia

2021 Year in Review - Multiple Myeloma

Preliminary data suggest that patients with both MM and WM show impaired serologic responses following COVID-19 vaccines, with more severe impairment of COVID-19 S-protein antibody responses observed in the Waldenström macroglobulinemia cohort, and mRNA-1273 eliciting higher responses than other vaccines.

Given the significant immunoparesis associated with multiple myeloma (MM) and Waldenström macroglobulinemia (WM) in patients, the current study evaluated COVID-19 vaccine responsiveness in patients with MM and WM. Results of this analysis were presented at the 2021 International Myeloma Workshop and summarized here.

Patients included in the analysis had received different vaccines, including BNT162b2 mRNA (Pfizer/BioNTech), mRNA-1273 (Moderna), or JNJ-78436735 (Johnson & Johnson). The primary end point was SARS-CoV-2 spike (S)-protein antibody detection 28 days after final vaccination. S-antibodies were detected with the Elecsys assay. Secondary end points included functional serologic assessments and T-cell responses at 28 days, 6 months, 9 months, and 12 months.

A total of 141 patients were enrolled. Of these, 136 patients had initial S-antibody assessment and were included in the analysis. Of these 136 evaluable patients, 91 patients had a diagnosis of MM and 45 of WM. Median antibody titer was 178.0 for MM and 3.96 for WM. S-antibody response rate was achieved in 91% of patients with MM and 60% of patients with WM. However, response rates for achieving S-antibody >100 U/mL were 56% in MM and 33% in WM.

Among the vaccines tested, mRNA-1273 elicited significantly higher S-antibody response rates in both the MM and WM cohorts. In patients with MM, vaccine-specific S-antibody response was 74% (25 of 34; P <.05) following mRNA-1273, 51% (24 of 47; P = not significant) following BNT162b2, and 20% (2 of 10; P <.05) following JNJ-78436735. In patients with WM, vaccine-specific S-antibody response was 67% (10 of 15; P <.005) following mRNA-1273, 19% (5 of 27; P <.05) following BNT162b2, and 0% (0 of 3; P = not significant) following JNJ-78436735.

In the MM cohort, improved S-antibody responses were associated with disease remission. S-antibody response >100 U/mL occurred in 65% (35 of 54) of patients who achieved very good partial response or better and 45% (9 of 20) in those with progressive disease; p100 U/mL occurred in 56% (31 of 55) and 53% (19 of 36), respectively.

In the WM cohort, S-antibody responses >100 U/mL were seen in previously untreated patients (8 of 11 [73%]; P <.05) but were suboptimal antibody responses for those who received rituximab in the past 12 months (0 of 8 [0%]; P <.05) or were on active Bruton tyrosine kinase inhibitors (4 of 14 [29%]; P = not significant).

These preliminary data suggest that patients with both MM and WM show impaired serologic responses following COVID-19 vaccines, with more severe impairment of COVID-19 S-antibody responses observed in the WM cohort, and mRNA-1273 eliciting higher responses than other vaccines.

Source: Branagan A, Lei M, Yee AJ, et al. COVID-19 vaccine responsiveness in patients with multiple myeloma and Waldenström macroglobulinemia. Clin Lymphoma Myeloma Leuk. 2021;21(suppl 2):S29.

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