Patients receiving cancer therapy experience iatrogenic immunosuppression which makes them more susceptible to severe COVID and simultaneously blunts their response to vaccines against SARS-CoV-2. Treatment related immunosuppression is often transient and/or cyclical which raises critical questions about how to optimally time vaccines and boosters in patients who are undergoing active cancer therapy. In our U54 SeroNet project, we have focused on accruing cancer patients undergoing active treatment. While patients with any cancer type were eligible, we oversampled patients either receiving B lineage depleting treatments, bone marrow transplant, and PD-1/PD-L1 immune check point inhibitors as we hypothesized these treatments were most likely to create immune altered states that would alter responses to SARS-CoV-2 vaccine or infection. As of July 8, 2022, we have enrolled 826 patients with cancer in our study, 738 (89%) of whom have received their primary vaccine series, 543 (74% of vaccinated) have received their first booster and 177 (33% of single boosted) have received their second booster. Our cohort is racially and ethnically diverse with 20% Hispanic, 9% Black, 9% Asian, and 6% mixed/other races, reflecting the diversity of patients who live in Los Angeles county. Among a subset of 657 cancer patients with serology data available, 53.9% and 38.1% of solid and hematologic cancer patients achieve high (IgG(S-RBD) >590 BAU/ml) antibody levels after completion of the primer series, which improves to 76.8% and 65.2% after boosting. Among patients with no seropositivity after priming, 83.3% seroconverted after a booster immunization (25.0% with high IgG-(S-RBD)). These data demonstrate that booster doses can improve serologic responses in patients immunosuppressed due to cancer therapy, however a substantial number of patients still have suboptimal serologic responses. Durability of the serological response, T cell/cellular immunity and resistance to breakthrough infection in this cohort are largely unknown