ABSTRACT
Purpose: Solid organ transplant (SOT) recipients mount suboptimal immune responses to a two-dose SARS-CoV-2 mRNA vaccine series. Data regarding antibody responses in HIV and SOT remains limited. We characterized spike binding antibody responses before and after an additional mRNA vaccine dose in SOT recipients, including in people with HIV (PWH). Method(s): Spike binding antibody titers were assessed before and one month after an additional vaccine dose using a quantitative ELISA. An additional vaccine dose was defined as a third dose of a mRNA vaccine primary series, as recommended by the CDC. Result(s): Antibody titers were assessed in 64 SOT recipients (58% kidney, 34% liver, 8% other). Participants had a median age of 57 and 47% were women. PWH comprised 14% of the cohort (9/64, 78% kidney). 70% (45/64) of SOT recipients developed antibodies after a two-dose vaccine series (62% kidney, 33% liver). The additional dose was given a median of 169 days (IQR 144.75-185.75 days) after the second vaccine dose, and 72% received three doses of BNT162b2 (Pfizer-BioNTech) while 28% received three doses of mRNA-1273 vaccine (Moderna). The median time between transplantation and an additional vaccine dose was 2.8 years (IQR, 0.6-8.9). 32% (6/19) of SOT recipients who had no detectable antibody seroconverted after receiving an additional vaccine dose. The 45 participants who were seropositive prior to the third dose displayed a median 4.4-fold increase in antibody titers. SOT recipients with HIV had comparable antibody responses to those without HIV. Conclusion(s): Our data indicate that SOT recipients benefit from an additional SARS-CoV-2 mRNA vaccine dose. SOT recipients with and without HIV appear to mount comparable antibody responses upon vaccination, although larger numbers are needed.
ABSTRACT
Background: Multiple myeloma (MM) patients are immunocompromised due to defects in humoral/cellular immunity and immunosuppressive therapy. Reports indicate that the antibody (Ab) response in MM after 1 dose of SARS-CoV-2 RNA vaccine is attenuated. The impact of treatment on cellular immunity after vaccination remains unknown. Methods: We analyzed SARS-CoV-2 spike-binding (anti-S) IgG level in 320 MM patients receiving SARS-CoV-2 RNA vaccination. Blood and saliva were taken at multiple time points and compared with serology data of 69 age-matched vaccinated healthcare workers. We profiled SARS-CoV-2-specific T cell responses in a subset of 45 MM patients and 12 age-matched healthy controls by flow cytometry and ELIspot. All subjects were enrolled in studies approved by the Institutional Review Board at the Icahn School of Medicine at Mount Sinai. Results: The 320 patients (median age 68 year) received two-dose RNA vaccines (69.1% BNT162b2, 27.2% mRNA-1273). Median time to diagnosis was 60 months with a median of 2 prior treatment lines (range 0-16). We included 23 patients with smoldering MM. Patients received various treatments at vaccination with 148 (43.8%) on anti-CD38-containing treatment, 36 (11.3%) on BCMA-targeted therapy and 59 (18.4%) not on active treatment (incl. SMM patients). At the last available evaluation prior to vaccination, 131 (40.9%) exhibited a complete response. At data cutoff, a total of 260 patients (81.3%) had anti-S IgG measured >10 days after the second vaccine (median 51 days). Of these, 84.2% mounted measurable anti-S IgG levels (median 149 AU/mL). In the control group, Ab levels were significantly higher (median 300 AU/mL). Ab levels in the vaccinated MM patients with prior COVID-19 were 10-fold higher than those of patients without prior COVID-19 (p<0.001). Repeat Ab measurements up to 60 days after second vaccination confirm delayed and suboptimal IgG kinetics, particularly in patients receiving anti-MM treatment compared to controls (Figure 1). MM patients on active treatment had lower anti-S IgG levels (p=0.004) compared to patients not on therapy (median 70 vs 183 AU/mL). Notably, 41 patients (15.8%) failed to develop detectable anti-S IgG: 24/41 (58.5%) were on anti-CD38, 13/41 (31.7%) on anti-BCMA bispecific Ab therapy and 4/41 (9.8%) >3 months after CAR T. Univariate analysis showed an association of disease-related factors with absence of anti-S IgG: more previous lines of treatment (>3 lines, p=0.035;>5 lines, p=0.009), receiving active MM treatment (p=0.005), grade 3 lymphopenia (p=0.018), receiving anti-CD38 therapy (p=0.042) and receiving BCMA-targeted therapy (p<0.001). Multivariate analysis (corrected for age, vaccine type, lines of treatment, time since diagnosis, response status and lymphopenia) confirmed that anti-CD38 (p=0.005) and BCMA-targeted treatment (p<0.001) are associated with not developing detectable anti-S IgG. Clinical relevance is emphasized by 10 cases of COVID-19 after 1 (n=7) or 2 vaccine doses (n=3, all without anti-S IgG) with 1 patient passing due to respiratory failure. We studied SARS-CoV-2-specific T cell responses >2 weeks after the second vaccine in 18 MM patients with undetectable anti-S IgG (seronegative), 27 with detectable anti-S IgG (seropositive) and 12 healthy seropositive controls. We found that seropositive MM patients had CD4+CD154+ T cells producing IFNg, TNFa and IL-2 at similar levels as controls, whereas in the seronegative MM cohort CD4 T cell responses were significantly reduced (p<0.005). SARS-CoV-2-specific CD8 T cell responses were overall weaker and not different across cohorts. This data suggests that absence of detectable IgG is associated with suboptimal response of humoral and cellular immunity. Conclusion: MM patients mount a suboptimal IgG response after SARS-CoV-2 vaccination, with 15.8% of patients without detectable anti-S IgG. Ongoing analyses will highlight durability of serological protection against COVID-19. Additional data on T cell responses and immunophenotyping in the context of vaccination will be upda ed at the meeting. Implications are continuation of non-pharmacological interventions, e.g. masking/social distancing, for vulnerable patients. The findings underscore a need for serological monitoring of MM patients after vaccination and for trials assessing use of prophylactic strategies or studies exploring additional immunization strategies. [Formula presented] Disclosures: Wang: Sanofi Genzyme: Consultancy. Chari: Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees;Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Millenium/Takeda: Consultancy, Research Funding;Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;Pharmacyclics: Research Funding;GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees;Secura Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Research Funding;Janssen Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Shattuck Labs: Consultancy, Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda: Consultancy, Research Funding;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cordon-Cardo: Kantaro: Patents & Royalties. Krammer: Kantaro: Patents & Royalties;Merck: Consultancy;Pfizer: Consultancy;Avimex: Consultancy;Seqirus: Consultancy. Jagannath: Legend Biotech: Consultancy;Karyopharm Therapeutics: Consultancy;Janssen Pharmaceuticals: Consultancy;Bristol Myers Squibb: Consultancy;Sanofi: Consultancy;Takeda: Consultancy. Simon: Kantaro: Patents & Royalties. Parekh: Foundation Medicine Inc: Consultancy;Amgen: Research Funding;PFIZER: Research Funding;CELGENE: Research Funding;Karyopharm Inv: Research Funding.