Second Booster BNT162b2 Restores SARS-CoV-2 Humoral Response in Patients With Multiple Myeloma, Excluding Those Under Anti-BCMA Therapy

Abstract

COVID-19 vaccination leads to a less intense humoral response in patients with multiple myeloma (MM) compared with healthy individuals, whereas the SARS-CoV-2-specific immunity fades over time. The purpose of this study was to explore the kinetics of SARS-CoV-2 neutralizing antibodies (NAbs) in patients with MM after vaccination with the BNT162b2 mRNA vaccine, focusing on their response before (B4D) and at 1 month after the fourth vaccination (M1P4D). Overall, 201 patients with a median age of 67 years were included, whereas 114 (56.7%) were men. The median NAbs levels B4D were 80.0% (±3.5%) and at M1P4D they increased to a median value of 96.1% (±3.7%). The NAb values at M1P4D were similar to those at 1 month post the third dose and superior to all previous timepoints. At M1P4D, the NAbs levels of all the treatment groups increased, apart from the anti-BCMA group. A significant increase in median NAbs values was observed for those receiving CD38-based treatment (n = 43, from 71.0% B4D to 96.0% at M1P4D) and those who did not receive CD38- or BCMA-targeted therapy (n = 137, from 89.6% B4D to 96.3% at M1P4D). Regarding the patients under BCMA-based therapy (n = 21), there was no remarkable increase in NAbs values following the second booster shot (from 3.0% B4D to 4.0% at M1P4D). In conclusion, booster vaccination with the BNT162b2 results in a substantially improved humoral response against SARS-CoV-2 in patients with MM. Anti-BCMA treatment remains an adverse predictive factor for NAbs response; thus, tailored prevention measures should be considered for this patient subgroup.

Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster Vaccination

“…We compared the Spike and Spike-RBD Ab magnitude and breadth and its ability to cross-neutralize WA1, Delta, and the Omicron variants BA.1, BA.2 and BA.4/5 following BNT162b2 in MM/WM patients and in HCW as reference. Analysis of HCW showed potent neutralization of WA1 and significantly lower NAb to Delta, BA1, BA.2 and BA.4/5, similar to previously reported data [ 25 , 33 , 34 , 35 , 36 ].…”

“…WM and MM cohorts having prior therapy showed improved responsiveness to the BNT162b2, although the response range was broad. These results expand and confirm previous reports on the adverse role of B-cell directed therapies on NAb activity against WA1 following booster COVID-19 vaccination [ 8 , 36 ]. Another recent study also showed similar results in patients with hematological cancer who received a booster mRNA-1273 shot at 5 months after the primary mRNA-1273 vaccination [ 37 ].…”

COVID-19 vaccination in patients with cancer: Opportunities and challenges

“…In patients with MM after vaccination with the BNT162b2 mRNA vaccine, focusing on their response before and at 1 month after the fourth vaccination. Booster vaccination with the BNT162b2 results in a substantially improved humoral response against SARS-CoV-2 in patients with MM ( 48 ).…”

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

“…If the study included a higher number of patients (currently n=33) there could have been a statistically significant improvement of the response, but the possibility that in these patients it is difficult to overcome the immunocompromised condition remains. In another report, although the fourth dose raised the level of neutralizing antibodies from 80 to 96% at one month after the booster in multiple myeloma patients, anti-BCMA (B cell maturation protein) treatment affected the level of neutralizing antibodies after the third and fourth vaccine dose (Ntanasis-Stathopoulos et al, 2022). In this group additional vaccine boosters seemed to even reduce the level of neutralizing antibodies (Ntanasis-Stathopoulos et al, 2022).…”

“…In another report, although the fourth dose raised the level of neutralizing antibodies from 80 to 96% at one month after the booster in multiple myeloma patients, anti-BCMA (B cell maturation protein) treatment affected the level of neutralizing antibodies after the third and fourth vaccine dose (Ntanasis-Stathopoulos et al, 2022). In this group additional vaccine boosters seemed to even reduce the level of neutralizing antibodies (Ntanasis-Stathopoulos et al, 2022). Similarly, in patients with lymphoid malignancies, anti-B cell therapies have reduced neutralizing antibodies after the fourth dose (Fendler et al, 2022).…”