medwireNews: Research from three countries adds support for the use of a booster dose of vaccines against SARS-CoV-2 in people with cancer, especially those undergoing active anticancer treatment.
All three studies report waning immunogenicity after the second dose of the Pfizer–BioNTech (BNT162b2) vaccine and a significant increase in immunoglobulin (Ig)G antibodies against SARS-CoV-2 antigens after a third dose.
The data from Israel
In the first study, 72 actively treated patients with cancer and 144 sex- and age-matched cancer-free individuals – all of whom had no history of COVID-19 – received a booster dose of the Pfizer–BioNTech vaccine between August and September 2021, at a median of 210 and 217 days, respectively, after their second dose.
As reported in a comment published in The Lancet Oncology, just over a quarter (28%) of the cancer patients were seronegative prior to the booster, compared with just 1% of the cancer-free controls, a significant difference. The corresponding proportions at around a month after the booster were 4% and 0%.
Both groups of patients experienced a significant rise in absolute concentrations of IgG antibodies against the spike protein after versus before the booster, but the increase was significantly lower in cancer patients than controls.
“Our presented data suggest a high rate of waning immunogenicity in patients with cancer approximately 6 months after the administration of the second dose of BNT162b2, and support the use of a booster dose in this vulnerable population of actively treated patients with cancer,” write Hagai Ligumsky and co-workers from Tel Aviv Sourasky Medical Center in Israel.
The Belgian results
The B-VOICE study from Belgium reported on 141 patients with a solid or hematologic malignancy who received a third dose of the Pfizer–BioNTech vaccine, the majority (97%) at an average of 183 days after the second dose. All but 20 patients (13 with a solid tumor, seven with a hematologic malignancy) were undergoing active anticancer therapy at the time of the third dose.
Peter van Dam (Antwerp University Hospital, Belgium) and colleagues found that levels of IgG antibodies against the SARS-CoV-2 receptor-binding domain in the overall cohort “had waned significantly” at 6 months versus 28 days after the second dose, at geometric mean titers of 65.8 and 386.2 BAU/mL, respectively.
But administration of a third dose led to a significant increase in IgG levels, with a geometric mean titer of 936.5 BAU/mL at 28 days after the third dose versus 386.2 BAU/mL after the second dose.
The results were similar when patients were stratified by treatment type (eg, targeted or hormonal therapy, and chemotherapy and/or immunotherapy), but the drop in IgG titers at the 6-month mark following the second dose was greatest for patients receiving rituximab, with levels remaining low even after the third dose, note the researchers in a letter to the European Journal of Cancer.
“Hence, the role of a third dose remains debatable in this population, although adaptive cellular immunity after vaccination might play a role in protecting these patients against SARS-CoV-2,” they add.
The team also highlights that “future research on post-vaccine antibody durability should be coupled to measurement of B-cell and T-cell responses over time” as the true serological correlates of protection have not yet been established.
The findings from France
The third study – by Charlotte Fenioux (Hôpital Henri Mondor, Créteil, France) and co-investigators – included 163 solid cancer patients on chemotherapy (75%), targeted therapy (16%), or immunotherapy (9%) who received two doses of the Pfizer–BioNTech vaccine 21 days apart between February and May 2021. Those with a weak humoral response (anti-spike antibodies <1000 AU/mL) a month after the second dose were offered a third dose.
The proportion of patients with anti-spike IgG titers over the cutoff of 1000 AU/mL rose from 15% at the time of the second dose to 65% at 28 days after the second dose, with respective median values at the two timepoints of 30.4 and 1996.3 AU/mL.
Of the 36 participants who received a third dose, 75% achieved antibody levels above 1000 AU/mL when assessed 28 days after administration. The median antibody titer was 7435.3 AU/mL.
By contrast, at the 3-month assessment after the second dose, almost half (42%) of the 64 evaluable patients who received just two doses had IgG titers below 1000 AU/mL, and the median titer was 1352.5 AU/mL.
“COVID-19 guidelines have evolved since this study was designed, and a third dose is now recommended at 6 months for adults older than 60 years,” write the researchers. “The results of this study suggest that a third dose of the SARS-CoV-2 vaccine could be needed at 1 month after the second dose in patients receiving active cancer treatment.”
Multivariable analysis identified receipt of chemotherapy or targeted therapy as a significant predictor of low anti-spike IgG antibodies, at an odds ratio of 5.4 relative to immunotherapy.
“Schedules of administration (daily, weekly, every 2 weeks, and every 3 weeks) and time between vaccination and intravenous chemotherapy administration (≤48 vs >48 hours) were not associated with the intensity of the humoral response,” report Fenioux et al in JAMA Oncology.
They continue: “This result must be confirmed in larger cohorts, because the organization of vaccination schedule and chemotherapy cycles is a daily challenge.”
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Lancet Oncol 2021; doi:10.1016/S1470-2045(21)00715-4
Eur J Cancer 2021; doi:10.1016/j.ejca.2021.12.025
JAMA Oncol 2022; doi:10.1001/jamaoncol.2021.7777