麻豆传媒

Barely one-quarter of patients with cancer obtained protection against COVID-19 after one dose of the Pfizer/BioNTech vaccine, a prospective study showed.

The data found a "strikingly low" 28% immune efficacy rate in patients with cancer, including 13% in patients with blood cancers. In contrast, first-dose seroconversion occurred in 97% of a healthy control group, Adrian Hayday, PhD, of King's College London, and co-authors concluded in a report posted to the preprint server .

A second dose at day 21, however, brought adequate immunity to nearly all the cancer patients, they said.

"These data support prioritization of cancer patients for an early (21-day) second dose of the BNT162b2 vaccine," Hayday and colleagues wrote in the preprint. "Given the globally poor responses to vaccination in patients with hematological cancers, post-vaccination serological testing, creation of herd immunity around these patients using a strategy of 'ring vaccination,' and careful follow-up should be prioritized."

"Delayed boosting potentially leaves most solid and hematological cancer patients wholly or partially unprotected, with implications for their own health, their environment, and the evolution of variant-of-concern strains," the researchers added. "Prompt boosting of solid cancer patients quickly overcomes the poor efficacy of the primary inoculum in solid cancer patients."

In general, patients with cancer have been excluded from clinical trials of COVID-19 vaccines, following of sustained immune dysregulation, inefficient seroconversion, and prolonged viral shedding after COVID-19 infection. The exclusion has raised questions about the vaccines' safety and efficacy in patients with cancer, Hayday and co-authors noted.

Moreover, British health officials changed the interval between the first and second dose to 12 weeks to maximize population coverage. Whether that interval is appropriate for patients with cancer, however, particularly those on systemic anti-cancer therapy, remains unclear, the authors continued.

To examine the issue, they prospectively studied 151 patients with cancer (solid tumors and hematologic malignancies) and 54 healthy individuals (mostly healthcare workers) who received an initial dose of the Pfizer/BioNTech vaccine against COVID-19. Blood samples were obtained from all study participants at baseline and at 3 and 5 weeks after vaccination.

In keeping with the British policies for COVID vaccination, participants vaccinated from Dec. 8 to 29 received two doses of vaccine, 30 days apart. Participants vaccinated after that received the initial dose and remained in follow-up to the planned booster dose 12 weeks later.

The primary endpoint was humoral and cellular immune response in the patients following the first vaccine injection. Immune efficacy was defined by antiviral IgG titers 21 days after the initial (priming) vaccine dose. The secondary endpoint was vaccine safety.

The patients with cancer had a median age of 73, and two thirds had one or more comorbid conditions. Solid malignancies accounted for 63% of the patient population and hematologic malignancies for 37%.

Most of the patients with solid tumors had late-stage disease associated with a cancer diagnosis exceeding 24 months. The healthy control group consisted of vaccine-eligible individuals who were not age-matched to the patients.

Among evaluable cancer patients, 31 received both vaccine doses and 118 received only the first dose. In the control group, 16 participants received both vaccine doses and the rest received only the priming dose.

To account for possible immune stimulation by past or concurrent infection, the researchers asked the patients with cancer to provide nose and throat swabs every 10 days. Because of the emergence of the B.1.1.7 variant and the national lockdown that started Jan. 4, only 79 patients were able to participate in screening for the entire study period, and only 12 had more than one swab test.

During the first 21 days after the priming dose, six patients developed COVID-19, including two patients who developed severe disease and died. No patient tested positive for the coronavirus after 21 days.

At 21 days post-priming dose, immune efficacy was poor, as antibody seroconversion had occurred in 39% of patients with solid tumors and 13% of those with hematologic malignancies.

"In sum, a priming inoculum ... induced seroconversion in the great majority of healthy controls but failed to achieve this in most solid and hematological cancer patients, with efficacy in the hematological cancer cohort being significantly worse than in solid cancer patients," the investigators wrote. "Moreover, not all seroconverted cancer patients showed virus neutralization."

Nonresponse correlated with reduced numbers of B cells in patients with solid or hematologic malignancies, the team added.

In a subgroup of patients with immune results after the priming and booster vaccine doses, all 12 patients in the control group achieved immune response after the booster dose, as did 18 of 19 patients with solid tumors, including eight patients who did not seroconvert after the priming dose. In contrast, nine of 21 patients without a booster dose had seroconverted.

Too few patients with hematologic malignancies were eligible for a booster dose to draw conclusions about the effects of the second dose.

With regard to safety, more than half the patients with cancer reported no toxicity after the first vaccine dose, as compared with 37.5% of the control group, the researchers reported. Among study participants evaluable after the booster dose, 71% of cancer patients and 31.25% of the control group reported no toxic effects. Additionally, 6.8% of the patients versus 50% of the control group reported both local and systemic effects after the booster dose.

The study is informative but has limited applicability to cancer patients in North America, where a 3- to 4-week interval remains the standard for currently available two-dose vaccines, said Justin Gainor, MD, of Massachusetts General Hospital Cancer Center in Boston. The applicability for patients who receive a single-dose vaccine, such as the Johnson & Johnson product, is also unclear.

"There are two fundamental questions about patients with cancer receiving a vaccine," he told 麻豆传媒. "The first, and more relevant question, is whether patients who receive a COVID vaccine are likely to develop immunity to the virus. We know that patients with malignancies, because of the underlying disease and the therapies they commonly receive, are more immunosuppressed. So it's a question of whether they can mount a sufficient immune response.

"That's distinct from the question of having one dose versus two for a vaccine that was designed for two doses. We shouldn't be deviating from how the studies were done, particularly in patients with cancer. That they should be getting two doses is the take-home point [of the study]."

Because of cancer patients' immunosuppressed condition, "it's absolutely critical to vaccinate them, and I think they should be moved to the top of the list in terms of priority," said Gainor.

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