Vaccination with the mRNA-1273 vaccine (Moderna) appears safe in patients with solid tumors receiving immunotherapy, chemotherapy, or chemoimmunotherapy. The seroconversion rate is high after 2 vaccinations and noninferior to controls, according to results from the VOICE study, which were presented by Sjoukje Oosting, MD, PhD, Medical Oncologist, University Medical Center Groningen, the Netherlands, during the 2021 European Society for Medical Oncology Congress.
Patients with cancer were rarely included in COVID-19 vaccine studies, and active systemic treatment was an exclusion criterion, noted Dr Oosting.
Chemotherapy and immunotherapy may affect the ability to develop an effective immune response to vaccination and may increase risk for adverse events (AEs) from vaccination, which prompted an investigation of the mRNA-1273 vaccine in a study with 4 adult cohorts. The cohorts included individuals without cancer (N = 246), and patients with solid tumors, who received immunotherapy (N = 135), chemotherapy (N = 246), or chemoimmunotherapy (N = 246).
All of the participants received 2 mRNA-1273 vaccinations 28 days apart. The primary end point was SARS-CoV-2 Spike S1-specific immunoglobulin G serum antibody response.
The median age of each cohort was 60 to 66 years. In the immunotherapy cohort, 66% of participants were male, whereas 66% of the chemotherapy cohort were female. More than 90% had an Eastern Cooperative Oncology Group performance status of 0 or 1.
Skin cancers were the most common malignancy in the immunotherapy group (48.9%), followed by urinary tract (24.4%) and respiratory tract (20.6%) cancers. In the chemotherapy cohort, breast (31%) and digestive tract (28.4%) were the most common cancer types. The chemoimmunotherapy cohort consisted almost exclusively of patients with lung cancer (97.2%). In the immunotherapy cohort, 73.3% of the patients were receiving treatment for stage IV cancer, versus 56.3% in the chemotherapy cohort and 93.7% in the chemoimmunotherapy cohort.
The antibody response rates on day 28 after the second vaccination were 100% for controls, 99.2% for those receiving immunotherapy, 97.4% for chemotherapy recipients, and 100% for chemoimmunotherapy recipients; this met the criterion for noninferiority compared with the controls, defined as a margin of 10% and an alpha of 0.05.
“However, it is unknown which concentration of binding antibodies represents protection,” said Dr Oosting. “Neutralizing antibody levels are predictive of immune protection from symptomatic COVID-19. Therefore, we assessed the correlation between neutralizing antibody titers and binding antibody concentrations, and there was a good correlation in each cohort.”
The threshold for adequate antibody response was determined to be 300 binding antibody units (BAU)/mL, because only 3% of the participants had a SARS-CoV-2–binding antibody concentration of >300 BAU/mL, whereas participants were negative for neutralizing antibodies.
“Applying this threshold allowed us to classify 99.6% of the controls as adequate responders to 2 vaccinations. This was the case for 93.1% in the immunotherapy group, 83.8% in the chemotherapy group, and 88.8% in the chemoimmunotherapy group,” she said.
After 1 vaccination, 66% of the controls and only approximately 33% of the patients with cancer had an adequate response. “Although these percentages are high and really encouraging, there is still a significant minority of the patients who do not have an adequate response after 2 vaccinations—up to 16.2% in the chemotherapy group,” Dr Oosting said.
Spike-specific T-cell responses were ELIspot assay. When a response was considered to increase by 2-fold or more in the number of spots from prevaccination to postvaccination, and ≥50 interferon gamma–producing, spot-forming cells per 106 peripheral blood mononuclear cells, “we find a T-cell response in almost one-half of the nonresponders (3/7) and the suboptimal responders [26/55] compared with 70.5% [105/149] of the adequate responders,” said Dr Oosting.
Systemic AEs were more frequent and more likely to be moderate or severe after the second vaccination, which was true for all cohorts, with no striking differences between them. All 16 serious AEs, most related to infection and fever, occurred in the patients with cancer. There were 20 AEs of special interest, including 10 deaths.