COVID Booster May Benefit Active-Treatment Cancer Patients

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A COVID-19 booster shot may be beneficial for patients with cancer who are undergoing treatment, according to new findings from an Isreali case-control study.

The seropositivity rate among the patients with cancer remained high (87%) about 4 months after the patients had received the second BNT162b2 (Pfizer/BioNTech) vaccination. However, the median IgG titer in the patients and the control persons who were without cancer decreased over time. Notably, in a previous analysis that the authors conducted and in the current one, the IgG titers were statistically significantly lower in the patients with cancer as compared to control persons.

The correlation between antibody levels following vaccination and clinical protection has yet to be proven, but the accumulating evidence supports antibody response as a possible correlate of disease protection.

"Our data can't predict if a third booster dose is necessary," said study author Salomon M. Stemmer, MD, professor at the Institute of Oncology of Rabin Medical Center, Petah Tikva, Israel. "It does seem quite logical that a booster dose will cause an increase in IgG levels."

The findings were published August 11 in a research letter in JAMA Oncology.

In their previous study, Stemmer and colleagues compared the rates of antispike antibody response to the initial shot of the BNT162b2 vaccine among 102 adults with solid-tumor cancers who were undergoing treatment with that of 78 healthy control persons. They found that a high percentage of patients undergoing treatment for cancer (90%) achieved a sufficient antibody response to the BNT162b2 vaccine.

Booster Endorsed

Responses to COVID-19 vaccination have varied among patients with cancer. For patients with solid tumors, responses have been good even while the patients were receiving systemic therapy. However, among patients with blood cancers, particularly those receiving immunosuppressive therapies, responses have been poor. Studies have identified factors associated with a poor response, but it has been unclear whether to recommend booster shots.

Earlier this month the US Food and Drug Administration (FDA) authorized a third dose of either the Pfizer or the Moderna COVID-19 vaccine for all individuals with compromised immune systems. Those eligible for a third dose include solid-organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.

IgR Titers Lower in Cancer Patients

In the current analysis, the authors evaluated the anti-S response in the patients with cancer approximately 4 months after they had received the second vaccine dose. They compared the responses in those patients with the responses in a control group.

The cohort included 95 patients from the prior study and 66 control persons. The most common malignancies were gastrointestinal (26%), lung (25%), and breast (18%).

All patients were receiving systemic therapy. Chemotherapy was the most common (28%), followed by immunotherapy (21%) and combination chemotherapy/biological therapy (20%).

At a median of 123 days after the second vaccination, 83 patients with cancer (87%) and all of the control patients (100%) were seropositive for anti-S IgG antibodies. The median titer levels were significantly lower among case patients as compared to control patients (417 AU/mL [interquartile range (IQR), 136 – 895] vs 1220 AU/mL [IQR, 588 – 1987]; P < .001)

There was a 3.6-fold range in median titer values across tumor types and an even wider range (8.8-fold) across the different types of treatment. The lowest titers were observed among patients who had received immunotherapy plus chemotherapy/biological therapy (median [IQR], 94.4 [49.4 – 191] AU/mL/147 [62.8 – 339] AU/mL).

In an exploratory multivariable analysis, treatments with chemotherapy plus immunotherapy and immunotherapy plus biological therapy were significantly associated with lower IgG titers.

No Downside for Cancer Patients

The Biden administration announced a plan to begin booster COVID-19 vaccinations for all American adults in September, with recommendations that the third vaccine be given at least 8 months after the second mRNA vaccine dose.

Jeremy M. Levin, DPhil, the chairman and CEO of Ovid Therapeutics Inc, explained that concerning boosters, "it is inconceivable that we will have all data at this stage.

"Knowledge about how boosters work and don't work and when you should ideally have them is imperfect," he told Medscape Medical News. "However, we can have a lot of confidence in the fact that hundreds of millions of people have received the vaccine, so we know a lot about the safety and efficacy."

Immunocompromised adults represent less than 5% of the total population, and most of the available data on vaccination are from patients who have undergone solid-organ transplant, Levin explained. Studies have shown that their response is less robust to vaccination in comparison with adults in the general population.

"Although it is still preliminary, the strongest data come from Israel," he said, "where they found that the booster was highly effective and doubled the number of transplant patients who developed antibodies."

But data are not yet available in the setting of cancer. "But even though we don't have the data yet, the answer is that no matter, the booster process is essential," he said. "The evidence we have is that boosters raise the immune response, and it is the best data we have now."

Martin J. Edelman, MD, chair, Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, noted that the current recommendation is that patients who are immunocompromised receive a booster immediately.

At his health system, this is interpreted to include patients who have undergone the following treatments: transplant (solid-organ and bone marrow transplant), hemodialysis, hematologic malignancy treatment, active immunosuppressive (chemotherapy, chemoimmunotherapy, and nonhormonal or single-agent immunotherapy) treatment, rheumatology treatments, and high-dose steroids.

"As for cancer patients, we are making arrangements to vaccinate patients who meet the above criteria now," he said. "There is no known downside to receiving booster immediately. While there may be less of a response than waiting for completion of treatment, we know that patients on active therapy are frequently able to mount a response, and any response is better than none."

Edelman added that this area is changing very rapidly. "We will modify our approach as information and guidance from appropriate organizations, such as the FDA and CDC, become available," he said.

Stemmer has received institutional research grants from CAN-FITE, AstraZeneca, Bioline RX, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelixis, Geicam, Incyte, Lilly, Moderna, Teva Pharmaceuticals, and Roche and owns stocks and options in CTG Pharma, DocBoxMD, Tyrnovo, VYPE, Cytora, and CAN-FITE. Edelman has received personal fees and other compensaiton from Windmil, personal fees from Biomarker Strategies, personal fees from AstraZeneca, personal fees from Takeda, personal fees, and other compensation from GlaxoSmithKline, Apexigen, Nektar, BMS, personal fees from Armo, personal fees from Bergen Bio, and other forms of compensation from Apexigen outside the submitted work. He has submitted a patent for epigenetic modifications to increase susceptibility to radiopharmaceuticals and is a paid advisor for Kanaph and Flame. Levin is chairman and CEO, Ovid Therapeutics Inc.

JAMA Oncol. Published online August 11, 2021. Full text

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