Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: The majority of solid tumour patients who have recently received chemotherapy, immunotherapy or a combination respond to two doses of the mRNA-1273 vaccine against SARS-CoV-2, the VOICE investigators reported at the ESMO Congress 2021.
Sjoukje Oosting, from University Medical Center Groningen in the Netherlands, presented the vaccine response rates for 131 patients given a PD-1 or PD-L1 inhibitor, 229 patients given cytotoxic chemotherapy with or without radiotherapy, and 143 patients given both immunotherapy and chemotherapy, as well as 240 cancer-free partners of the participating patients (controls).
The patients all had solid tumours, with 56.3–93.7% of each group having stage IV disease. Of note, 48.9% of immunotherapy-treated patients were diagnosed with skin cancer and over half of the patients were given chemotherapy for breast (31.0%) or digestive (28.4%) tumours, while 97.2% of combination-treated patients had lung cancer. Patients had received immunotherapy within 3 months of their first vaccine dose or chemotherapy within 4 weeks, she stated.
The primary endpoint of antibody response was defined as an IgG antibody level against the virus spike protein of 10 binding antibody units (BAU)/mL or above on day 28 after receipt of the second vaccination and this was measured among patients who were seronegative at baseline (≤10 BAU/mL).
This IgG antibody level was achieved by 99.2% of immunotherapy-treated patients, 97.4% of those given chemotherapy, and 100% of patients given both types of treatment; these levels were statistically noninferior to the 100% rate among controls.
Sjoukje Oosting observed that the threshold for binding antibodies that translates to protection against symptomatic COVID-19 is unknown but that neutralising antibodies are predictive of this effect, with a neutralising titre of at least 40 considered to be adequate.
This titre of neutralising antibodies significantly correlated with a binding antibody concentration of 230 BAU/mL in the study groups. Using the upper boundary of the 95% confidence interval as a guide, the team classified an adequate response to be 300 BAU/mL.
This threshold was met by 37.1% of immunotherapy-treated patients at day 28 after the first vaccination, rising to 93.1% on day 28 after the second vaccination, with corresponding rates for the chemotherapy arm of 32.5% and 83.8% and for the combination treatment arm of 33.3% and 88.8%. Among controls, 66.0% achieved the 300 BAU/mL threshold on first vaccination and 99.6% on the second.
Thus, two vaccinations failed to achieve adequate binding antibody levels in 6.9%, 16.2% and 11.2% of the immunotherapy, chemotherapy and combination therapy groups versus 0.4% of controls, said Sjoukje Oosting.
The researchers measured spike-specific T-cell responses in participants without a response to vaccination (n=7), with a suboptimal response (n=55) and with an adequate response (n=149).
Noting that “there is no consensus on a definition for a pharma-specific T cell response”, the researchers defined this outcome as an interferon (INF)-γ ELIspot assay threshold of a twofold or higher increase in spots from pre- to post-vaccination and a rate of 50 or above IFN-γ producing spot-forming cells per 106 peripheral blood mononuclear cells.
Overall, 42.9% of nonresponders had a T-cell response to vaccination with this criteria, as did 47.3% of suboptimal and 70.5% of adequate responders.
Discussing the safety findings, the presenter said “systemic adverse events [AEs] were more frequent and more likely to be moderate or severe after the second vaccination”, adding that “there were no striking differences between the cohorts.”
Sixteen serious AEs were reported in the patients within 7 days of vaccination, mainly related to infection or fever, and 20 AEs of special interest, including 10 deaths, of which eight were attributed to progressive disease, one to acute myeloid leukaemia and one to treatment-resistant pneumonitis.
There were also two cases of thromboembolism and one case of Stevens–Johnson syndrome that were considered potentially related to vaccination, although the latter was most likely caused by checkpoint inhibitor therapy, Sjoukje Oosting commented.
And she remarked that the 13 immune-related AEs recorded, such as pneumonitis, “were in line with what you would expect without vaccination.”
The investigator concluded that the mRNA-1273 vaccination is “safe” in patients receiving solid tumour therapy, with a “very high” seroconversion rate after two vaccinations, and although a “significant minority” of patients may not achieve an “adequate antibody response”, almost half of these patients have a spike-specific T-cell response.
Sjoukje Oosting concluded: “Longer follow-up of our study will indicate if there is a difference in the duration of immune response between the patients and the controls.”
LBA8 - Oosting S, Van der Veldt AAM, GeurtsvanKessel CH, et al. Vaccination against SARS-CoV-2 in patients receiving chemotherapy, immunotherapy, or chemo-immunotherapy for solid tumors. Ann Oncol 2021;32(suppl_5): S1283–S1346. doi:10.1016/annonc/annonc741
medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2021 Springer Healthcare part of the Springer Nature group