Cancer patients and survivors in Singapore derived significant protection from severe COVID-19 after three or four vaccine doses for at least 5 months, according to a nationwide study published today in JAMA Oncology.
Led by National Cancer Centre Singapore researchers, the multicenter study involved 23,217 cancer patients undergoing treatment, 50,391 cancer survivors, and 621,475 matched controls during the SARS-CoV-2 Delta variant wave (September 15 to December 2021) and the Omicron surge (January 20 to November 11, 2022).
The average age was 62.7 years for actively treated cancer patients, 62.9 years for cancer survivors, and 61.8 years for controls. Of all patients with cancer, 63.1% were women, 81.6% were Chinese, 10.1% were Malay, 6.2% were Indian, and 2.0% were of other races. By study end, 84.8% of participants had received at least two doses of an mRNA COVID-19 vaccine.
Four doses better than 3
The incidence rate ratios (IRRs) for the third- and fourth-dose group compared with the two-dose group for severe COVID-19 and hospitalization were much lower during both the Delta and Omicron surges in both cancer patients and controls.
The IRRs for severe outcomes among three-dose recipients were 0.14, 0.13, and 0.07 for patients undergoing treatment, cancer survivors, and controls, respectively. The IRRs for severe illness among four-dose recipients during the Omicron wave were lower (0.13, 0.10, and 0.10, respectively).
While zero- or one-dose vaccine recipients had similar rates of COVID-19 infection as two-dose recipients, the former group had significantly higher rates of severe COVID-19 among both actively treated patients and cancer survivors during both Delta (IRR, 3.86 and 10.07, respectively) and Omicron (IRR, 1.85 and 1.56), although the Omicron finding in the active-treatment group was not statistically significant.
"This highlights the increased vulnerability of patients with cancer to adverse outcomes from COVID-19, with risk of severe disease further compounded in the absence of vaccination," the researchers wrote.
Three vaccine doses were significantly protective against severe COVID-19 and hospitalization in both cancer and control groups, with lower IRRs than in the two-dose group amid the Delta and Omicron waves.
This highlights the increased vulnerability of patients with cancer to adverse outcomes from COVID-19, with risk of severe disease further compounded in the absence of vaccination.
The IRR against severe COVID-19 was higher in the active-treatment cohort than among controls during both Delta (IRR, 0.14 vs 0.07) and Omicron (IRR, 0.27 vs 0.18), but cancer survivors had similar IRRs to controls (IRR, 0.13 vs 0.07 during Delta, 0.18 vs 0.18 during Omicron).
Lower IRRs against severe illness in the four-dose versus the third-dose group during Omicron suggested that the fourth dose conferred added protection, the study authors said. "In particular, the IRR for severe disease was significantly lower during infection 8 to 59 days after the fourth dose compared with 8 to 59 days after the third dose, suggesting a fourth dose provides additional protection," they wrote.
The IRRs against hospitalization were significantly lower in the four-dose than in the three-dose group in the active treatment (0.24 vs 0.45), cancer survivor (0.15 vs 0.27), and control groups (0.21 vs 0.29), which the researchers said suggests that a fourth vaccine dose confers added protection against hospitalization, regardless of cancer and treatment status.
No waning for at least 5 months
Vaccine effectiveness against poor outcomes and hospitalization didn't wane beyond 5 months after receipt of the third dose or up to 5 months after the fourth dose. "However, small numbers may limit interpretation of these results, given only 0.2% of patients in the 4-dose group manifested the outcome of severe disease," the authors wrote.
The findings demonstrate the benefits of early vaccination and the receipt of booster doses in cancer patients, the researchers said.
"The findings also provided insight into the longevity of vaccine-mediated protection against clinical infection outcomes in both immunocompromised patients with cancer with or without active treatment and the general population," they concluded.
"As the world moves toward living with COVID-19, evidence of the booster third and fourth vaccine dose and efficacy in overcoming waning immunity is imperative to guide the optimum protection for our most vulnerable patients."