Patients with solid tumors undergoing treatments with chemotherapy, immunotherapy, or chemoimmunotherapy mounted an adequate antibody response to the mRNA-1273 COVID-19 vaccine.
Investigators reported that the mRNA-1273 COVID-19 vaccine induced adequate antibody responses in patients with solid tumors who are undergoing treatment with chemotherapy, immunotherapy, or chemoimmunotherapy, according to findings from the VOICE trial (NCT04715438) published in The Lancet Oncology.
In cohort A—patients without cancer— the antibody response rate was 100% (95% CI, 98% to 100%) of more than 10 BAU/mL. Moreover, patient in cohort B—patients with solid tumors treated with immunotherapy—had an antibody response rate of 99% (95% CI, 96% to >99%). The rate in cohort C—patients with solid tumors treated with chemotherapy—was 97% (95% CI, 94%-99%), and the rate was 100% (95% CI, 97%-100%) for cohort D—patients with solid tumors receiving chemoimmunotherapy.
A total of 791 patients enrolled on the trial, with a median follow-up of 122 days. A total of 743 patients were evaluable for response, including 240 from cohort A, 131 from cohort B, 299 from cohort C, and 143 from cohort D. Target accrual for cohort C was not reached, although 205 evaluable patients were necessary to power calculations. Moreover, cohort D also did not reach its target accrual. In cohort C, 17% of patients received chemoradiotherapy. After the first vaccination, 1 patient in cohort C was diagnosed with COVID-19.
A total of 69% (95% CI, 52%-84%) of patients in cohort A had a spike-specific T-cell response along with 67% (95% CI, 51%-80%) of patients in cohort B, 66% (95% CI, 54%-76%) in cohort C, and 53% (95% CI, 38%-67%) in cohort D. Four patients (95% CI, <1% to 4%) in cohort C did not develop an antibody or T-cell response.
The post-hoc analysis after day 28 of the second vaccination had a cut off value of 300 BAU/mL to differentiate between adequate responders (>300 BAU/mL) and suboptimal responders (>10 BAU/mL). Investigators reported that over 99% (95% CI, 98% to >99%) of patients in cohort A, 93% (95% CI, 87%-97%) in cohort B, 84% (95% CI, 78%-88%) in cohort C, and 89% (95% CI, 82%-93%) in cohort D were adequate responders. Moreover, 7% of those in cohort B, 16% in cohort C, and 11% in cohort D were suboptimal responders or non-responders. Adequate response was observed 28 days after the first vaccination in 66% (95% CI, 60%-72%) of patients in cohort A, 37% (95% CI, 29%-46%) in cohort B, 32% (95% CI, 27%-39%) in cohort C, and 33% (95% CI, 26% to 41%) in cohort D.
Overall, 761 patients in cohort A experienced solicited adverse effects (AEs) following first vaccination, 132 in cohort B, 232 in cohort C, and 158 in cohort D, along with 750 who received the second vaccination. Solicited systemic AEs were higher up to 7 days following second vaccination vs first vaccination, including fatigue, fever, chills, headache, myalgia, joint pain, and nausea.
The most prevalent AE was fatigue after the first and second vaccinations in 26% and 54% in cohort A, 23% and 59% in cohort B, 31% and 49% in cohort C, and 36% and 48% in cohort D. Pain at the ejection site was also reported after the first and second vaccination in 21% and 4% in cohort A, 11% and 6% in cohort B, 10% and 5% in cohort C, and 26% and 6% in cohort D. In cohorts A, C, and D, pain at the injection site was more common compared with cohort B where erythema and induration at the injection site were uncommon after both vaccinations.
Grade 3 or higher serious AEs occurred in 0% of patients in cohort A, 2% in cohort B, 2% in cohort C, and 1% in cohort D. Serious AEs included fever, diarrhea, and febrile neutropenia. Ten patients had died at data cutoff, with 8 from disease progression, 1 from pneumonitis, and 1 from leukemia as a second malignancy.
AEs of special interest included thromboembolic events, myocardial infarction, convulsion, and erythema multiforme after the first vaccination which progressed to Stevens-Johns syndrome after the second. This was resolved with high-dose steroids. Immune-related AEs occurred in 4% of patients treated with immunotherapy, and 4% treated with chemoimmunotherapy. One patient died from pneumonitis, 1 patient developed grade 3 adrenal insufficiency, and 1 patient had grade 3 thrombocytopenia which required high-dose steroids.
Oosting SF, van der Veldt AAM, GeurtsvanKessel CH, et al. mRNA-1273 COVID-19 vaccination in patients receiving chemotherapy, immunotherapy, or chemoimmunotherapy for solid tumours: a prospective, multicentre, non-inferiority trial. Lancet Oncol. 2021;22(12):1681-1691. doi:10.1016/S1470-2045(21)00574-X