Safety and immunogenicity of a third dose of mRNA-1273 vaccine among cancer patients.

BACKGROUND: Compared to the general population, cancer patients are at higher risk of morbidity and mortality following SARS-CoV-2 infection. The immune response to a two-dose regimen of mRNA vaccines in cancer patients is generally lower than in immunocompetent individuals. Booster doses may meaningfully augment immune response in this population. We conducted an observational study with the primary objective of determining the immunogenicity of vaccine dose three (100 µg) of mRNA-1273 among cancer patients and a secondary objective of evaluating safety at 14 and 28 days. METHODS: The mRNA-1273 vaccine was administered ∼7 to 9 months after administering two vaccine doses (i.e., the primary series). Immune responses (enzyme-linked immunosorbent assay [ELISA]) were assessed 28 days post-dose three. Adverse events were collected at days 14 (± 5) and 28 (+5) post-dose three. Fisher exact or X2 tests were used to compare SARS-CoV-2 antibody positivity rates, and paired t-tests were used to compare SARS-CoV-2 antibody geometric mean titers (GMTs) across different time intervals. RESULTS: Among 284 adults diagnosed with solid tumors or hematologic malignancies, dose three of mRNA-1273 increased the percentage of patients seropositive for SARS-CoV-2 antibody from 81.7% pre-dose three to 94.4% 28 days post-dose three. GMTs increased 19.0-fold (15.8-22.8). Patients with lymphoid cancers or solid tumors had the lowest and highest antibody titers post-dose three, respectively. Antibody responses after dose three were reduced among those who received anti-CD20 antibody treatment, had lower total lymphocyte counts and received anticancer therapy within 3 months. Among patients seronegative for SARS-CoV-2 antibody pre-dose three, 69.2% seroconverted after dose three. A majority (70.4%) experienced mostly mild, transient adverse reactions within 14 days of dose three, whereas severe treatment-emergent events within 28 days were very rare (<2%). CONCLUSION: Dose three of the mRNA-1273 vaccine was well-tolerated and augmented SARS-CoV-2 seropositivity in cancer patients, especially those who did not seroconvert post-dose two or whose GMTs significantly waned post-dose two. Lymphoid cancer patients experienced lower humoral responses to dose three of the mRNA-1273 vaccine, suggesting that timely access to boosters is important for this population.