Low clinical protective response to SARS-CoV-2 mRNA COVID-19 vaccine in patients with multiple myeloma

Abstract

We conducted a prospective, three-center, observational study in Japan to evaluate the prevalence of seropositivity and clinically protective titer after coronavirus disease 2019 vaccination in patients with plasma cell dyscrasia(PCD). Two-hundred sixty-nine patients with PCD [206 symptomatic multiple myeloma (MM)] were evaluated. Seropositivity was observed in 88.7% and a clinically protective titer in 38.3% of MM patients, both of which were significantly lower than those of healthy controls. Patients receiving anti-CD38 antibodies had much lower antibody titers, but antibody titers recovered in those who underwent a wash-out period before vaccine administration. Older age (≥65), anti-CD38 antibody administration, immunomodulatory drugs use, lymphopenia (<1000/μL), and lower polyclonal IgG (<550 mg/dL) had a negative impact for the sufficient antibody production according to multivariate analysis. Patients with clinically protective titer had a significantly higher number of CD19+ lymphocytes than those with lower antibody responses (114 vs. 35/μL, p = 0.016). Our results suggested that patients with PCD should be vaccinated, and that the ideal protocol is to temporarily interrupt anti-CD38 antibody therapy for a “wash-out” period of a few months, followed by a (booster) vaccine after the B-cells have recovery. Supplementary Information The online version contains supplementary material available at 10.1007/s12185-022-03300-4.

Antibody and T‐cell responses by ultra‐deep T‐cell receptor immunosequencing after COVID‐19 vaccination in patients with plasma cell dyscrasias

“…Using commercially available anti‐spike antibody testing, we observed that ~85% of our patients with PCD mounted a positive serological response within 6 months of completing the initial vaccination series, comparable to other previous studies 11–18 . In studies assessing neutralising antibodies, the serological response has been lower, ranging from 41% to 74% 12,19–22 .…”

“…Using commercially available anti‐spike antibody testing, we observed that ~85% of our patients with PCD mounted a positive serological response within 6 months of completing the initial vaccination series, comparable to other previous studies. 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 In studies assessing neutralising antibodies, the serological response has been lower, ranging from 41% to 74%. 12 , 19 , 20 , 21 , 22 Although the presence and titre of neutralising antibodies may more directly reflect viral protection, these assays are not widely available in clinical practice.…”

Comparative analysis of humoral responses to BNT162b2 vaccine among patients with hematologic disorders and organ transplant recipients.

“…Our results also imply an inferior response among anti-CD38 therapy recipients. A negative impact of anti-CD38 therapy on vaccine efficacy was previously described by some studies [ 29 , 36 , 37 ] and denied by another [ 38 ]. However, it may be difficult to draw either conclusion from our results due to the underrepresentation of multiple myeloma in our cohort and because other effects of concomitant treatments, such as immunomodulatory drugs were not analyzed.…”

“…On the other hand, a growing body of studies suggests that the humoral response to COVID-19 vaccination may be suboptimal among a group that include people with hematological malignancies [ 1 , [17] , [18] , [19] , [20] ], chronic kidney failures [ 21 , 22 ], and organ transplant recipients [ [23] , [24] , [25] , [26] , [27] ]. Moreover, the degrees of impairment of the serological response within an at-risk group are often dependent on the treatment status and timing of vaccination [ [28] , [29] , [30] , [31] ], implying that risk-based vaccination is required. Although many of these studies help raise the alert to the poorer humoral response of at-risk individuals in comparison to healthy individuals, comparative risk analyses between the high-risk groups seems to be rather limited.…”

Prevalence and clinical outcome of Omicron breakthrough infection in patients with hematologic disease: a prospective observational cohort study

“…We previously reported the longitudinal humoral response after the second (D2) and third-doses (D3) of mRNA vaccination in consecutive patients with HD and compared it to that of health care workers (HCW). 13,14 We measured the anti-SARS-CoV-2 antibody titers of spike antigen (anti-S) and nucleocapsid antigen (anti-N) (Elecsys Anti-SARS-CoV-2 ECLIA, Roche Diagnostics, Burgess Hill, UK) after second dose (post-D2), before (pre-D3) and after third dose (post-D3) vaccination between July 2021 and September 2022. In this study, we investigated the incidence of newly con rmed Omicron breakthrough infection among the fully vaccinated (≥ D2) participants from January 1 through September 30, 2022.…”