Efficacy and longevity of immune response to 3rd COVID-19 vaccine and effectiveness of a 4th dose in severely immunocompromised patients with cancer (preprint)

Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. We demonstrate that a 3 rd dose of COVID-19 vaccine leads to seroconversion in 57% of patients that were seronegative after primary vaccination. The immune response is durable as assessed by anti-S antibody titers, T-cell activity and neutralization activity against wild-type SARS-CoV2 and BA1.1.529 at 6 months of follow up. A subset of severely immunocompromised hematologic malignancy patients were unable to mount adequate immune response after the 3 rd dose and were treated with a 4 th dose in a prospective clinical trial which led to adequate immune-boost in 67% of patients. Low baseline IgM levels and CD19 counts were associated with inadequate seroconversion. Booster doses induced limited neutralization activity against the Omicron variant. These results indicate that vaccine booster-induced immunity is durable in cancer patients and additional doses can further stimulate immunity in a subset of hematologic malignancy patients. Statement of significance We demonstrate that a 3 rd dose of vaccine leads to seroconversion in 57% of negative patients with durable immune responses at 6 months. A 4 th dose of vaccine can seroconvert hematologic malignancy patients with higher baseline IgM and CD19 levels.

High Seroconversion Rates Amongst Black and Hispanics With Hematologic Malignancies after SARS-CoV-2 Vaccination (preprint)

It is well established that COVID-19 carries a higher risk of morbidity and mortality in patients with hematologic malignancies, however, very little data on ethnicity specific responses in this particular patient population currently exist. We established a program of rapid vaccination and evaluation of antibody-mediated response to all EUA COVID-19 vaccines in an inner city minority population to determine the factors that contribute to the poor seroconversion to COVID-19 vaccination in this population. We conducted a cross-sectional cohort study of 126 patients with hematologic malignancies in the outpatient practices of our institution who completed their vaccination series with one of the three FDA EUA COVID-19 vaccines, Moderna, Pfizer, or Johnson & Johnson (J&J). We qualitatively measured Spike IgG production in all patients using the AdviseDx SARS-CoV-2 IgG II assay and quantitatively in 106 patients who completed their vaccination series with at least 14 days after the 2nd dose of the Moderna or Pfizer vaccines or 28d after the single J&J vaccine. Patient characteristics were analyzed using standard descriptive statistics and associations between patient characteristics, cancer subtypes, treatments, and vaccine response were assessed using Fisher Exact test or Kruskal-Wallis Rank Sum test. The majority of patients (74%) were minorities. Seventy patients (60%) received Pfizer, 36 patients (31%) Moderna, and 10 patients (9%) J&J. We observed a high-rate of seropositivity (86%) with 16 pts (14%) having a negative Spike IgG. Of the 86 minority patients included, 94% Blacks (30/32) and 87% (39/45) Hispanics showed seropositivity. The factors that contributed to significantly lower seroconversion rates included patients with Non-Hodgkin lymphoma (p=0.005), those who received cytotoxic chemotherapy (p=0.002), IVIG (p=0.01), CAR-T cell therapy (p=0.00002), and CD20 monoclonal antibodies (Ab) (p=0.0000008). Plasma cell neoplasms (p=0.02), immunomodulatory agents (p=0.01), and proteasome inhibitors (p=0.01) had significantly higher seroconversion rates, and those with a history of prior COVID-19 (11%, 12/106) had significantly higher antibody titers (p=0.0003). The positivity rate was 86% (37 seropositive, 6 seronegative) for autologous HSCT and 75% (3 seropositive, 1 seronegative) for allogeneic HSCT. No life-threatening AE were observed. We show high seroconversion rates after SARS-CoV-2 vaccination in non-White patients with hematologic malignancies treated with a wide spectrum of therapeutic modalities. Vaccination is safe, effective, and should be encouraged in most patients with hematologic malignancies. Our minorities based study could be employed as an educational tool to dispel myths and provide data driven evidence to overcome vaccine hesitancy.

Seroconversion rates following COVID-19 vaccination amongst patients with malignant disease- the impact of diagnosis and cancer-directed therapies (preprint)

As COVID-19 has been shown to adversely affect patients with cancer, prophylactic strategies are critically needed. We determined the immunogenicity of COVID-19 vaccination in a cohort of cancer patients that had received full dosing with one of the FDA-approved COVID-19 vaccines. 201 oncology patients underwent anti-spike protein SARS-CoV-2 IgG testing post vaccination and demonstrated a high rate of seroconversion (94%) overall. When compared to solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematological malignancies (85%), particularly recipients of anti-CD20 therapies (70%) and stem cell transplantation (74%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post-vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post-vaccination. Relatively lower IgG titers were noted following vaccination with the adenoviral when compared to the mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify vulnerable cohorts that need novel vaccination or passive immunization strategies.

Patterns of seroconversion for SARS-CoV2-IgG in patients with malignant disease and association with anti-cancer therapy (preprint)

Patients with cancer have been identified in several studies to be at high risk of developing severe COVID-19; however, rates of SARS-CoV-2 IgG seroconversion and its association with cancer types and anti-cancer therapy remain obscure. We conducted a retrospective cohort study in patients with cancer that underwent SARS-CoV-2 IgG testing. Two hundred and sixty-one cancer patients underwent SARS-CoV-2 IgG testing and demonstrated a high rate of seroconversion (92%). However, significantly lower seroconversion was observed in patients with hematologic malignancies (82%), patients that received anti-CD-20 antibody therapy (59%), CAR-T/cellular therapy (33%) and stem cell transplant (60%). Interestingly, all 17 patients that received immunotherapy, including 16 that received anti-PD-1/PD-L1 monoclonal antibodies, developed SARS-Cov-2 IgG antibodies (100% seroconversion). These data show differential rates of seroconversion in specific patient groups and bear importance for clinical monitoring and vaccination strategies that are being developed to mitigate the COVID-19 pandemic