Responses to COVID-19 Vaccines in Cancer Patients: Impact of Tumor and Treatment Type

Cancer patients have been underrepresented in clinical trials of COVID-19 vaccines, so it hasn’t been clear how well the vaccines protect these patients.¹

However, researchers have conducted several studies measuring indicators of COVID-19 protection in cancer patients, including the production of anti-SARS-CoV-2 antibodies and memory B- and T-cell levels after vaccination.^2-6

The studies have generally suggested that most patients with solid tumors produce antibodies and mount cellular responses. However, there is a subset of patients who fail to respond, and the strength of their response appears lower overall than that of healthy individuals. 

Furthermore, patients with hematologic malignancies appear less likely than those with solid tumors to have detectable immune responses. The studies have also suggested that patients receiving certain anticancer therapies, particularly chemotherapy, may have a higher risk of an impaired response to vaccination. 

Results by Cancer and Treatment Type

In one study, Ehmsen et al assessed anti-SARS-CoV-2 spike immunoglobulin G (IgG) antibody responses and T-cell responses in cancer patients who received the Pfizer-BioNTech vaccine or the Moderna vaccine.² The study included 201 patients with solid tumors and 323 with hematologic malignancies. 

At 36 days after the second vaccine dose, the seropositivity rate was 93% in patients with solid tumors and 66% in patients with hematologic malignancies (P =.004). Patients were more likely to be seronegative if they received anti-CD20 therapy, BTK inhibitor therapy, or chemotherapy.

Among solid tumor patients, 46% had a T-cell response, 76% of whom had both CD4+ and CD8+ T-cell responses. Among patients with hematologic malignancies, 45% had a T-cell response, 81% of whom had both CD4+ and CD8+ T-cell responses. 

In another study, Addeo et al measured anti-SARS-CoV-2 spike IgG antibody titers in 106 patients with solid tumors and 25 with hematologic malignancies who received the Pfizer-BioNTech or Moderna vaccine.³ 

After the second vaccination, the rate of seroconversion was significantly lower in the hematologic malignancy group than in the solid tumor group (77% vs 98%, P =.002). Median antibody titers were significantly lower in the hematologic malignancy group as well (832 U/mL vs >2500 U/mL; P =.029).

When compared with patients not on active therapy, antibody titer levels were significantly lower among patients who received cytotoxic chemotherapy (P =.019) or monoclonal antibody therapy (P =.029) within 6 months before the first vaccine dose. There were 4 patients who had received anti-CD20 therapy, and all were seronegative. 

In a third study, Ligumsky et al measured anti-SARS-CoV-2 spike IgG antibody titers after 2 doses of the Pfizer-BioNTech vaccine, comparing 164 healthy adults with 326 patients who had solid tumors and were treated with anticancer therapies.⁴ 

The rate of seronegativity was significantly higher in the cancer group than in the control group (11.9% vs 3.0%; P =.001), and the median antibody titers were significantly lower in the cancer group than in the control group (931 AU/ml vs 2817 AU/ml, P =.003). 

The rate of seronegativity was higher in patients treated with chemotherapy (18.8%) than in patients who received checkpoint inhibitors (9.1%) and those who received targeted therapy (2.6%; P =.02). 

The median IgG titers were also significantly different across treatment types — 578 AU/ml with chemotherapy, 793 AU/ml with immune checkpoint inhibitors, and 1895 AU/ml with targeted therapy (P =.002). 

In a fourth study, Thakkar et al assessed responses to vaccination with the Pfizer-BioNTech, Moderna, or Johnson & Johnson vaccine. Seroconversion rates were 98% among the 134 patients with solid tumors and 85% among the 66 patients with hematologic malignancies (P =.001).⁵ 

The rate of seroconversion was significantly lower in patients on active chemotherapy than in all other cancer patients (92% vs 99%; P =.04). Rates of seroconversion were high in patients who received hormone therapy (100%) or immune checkpoint inhibitors (97%) but lower in patients who received a stem cell transplant (73%), anti-CD20 therapies (70%), or chimeric antigen receptor T-cell therapy (0%). 

In a preprint article that has yet to be peer reviewed, Shroff et al reported immune responses to the Pfizer-BioNTech vaccine, comparing 50 healthy control individuals and 53 patients with solid tumors who were receiving chemotherapy.⁶ 

The researchers found that 67% of the cancer patients developed neutralizing antibodies after the first immunization, and that number went up to 80% after the second immunization. In comparison, 98% and 100% of the healthy control individuals had detectable neutralizing antibodies after the first and second immunizations, respectively. 

“When you look at the totality of the data, I think it is fair to say that patients who are immunocompromised, whether that be active cancer therapy, hematologic malignancy, solid tumor, and then frankly even organ transplant, do not have the same immunity,” said lead author of the preprint Rachna Shroff, MD, medical director of the University of Arizona Cancer Center Clinical Trials Office in Tucson.⁶ 

Dr Shroff added that these data probably contributed to the US Food and Drug Administration’s recent decision to authorize an additional dose of COVID-19 vaccines for immunocompromised people.⁷ 

Certain cancer patients fall into this category.⁸ This includes patients with solid tumors receiving chemotherapy — and, in some cases, immunotherapy — currently or within the last 6 months. It also includes patients receiving treatment for hematologic malignancies now or within the last 6 months. 

Boosting Immunity

Researchers are currently investigating the efficacy of a third vaccine dose for cancer patients in a study at Montefiore Medical Center in New York City. The researchers are screening cancer patients at Montefiore to identify those who do not have detectable antibodies 2 weeks after immunization with the Pfizer-BioNTech, Moderna, or Johnson & Johnson vaccine. 

The researchers are giving those patients an additional dose of the Pfizer-BioNTech vaccine and checking their antibodies 4 weeks after the additional dose. 

The study will probably enroll more patients with hematologic malignancies than solid tumors because solid tumor patients are more likely to develop antibodies following immunization, noted Astha Thakkar, MD, a hematology-oncology fellow at Montefiore Medical Center who is involved in the booster study and is the lead author of one of the aforementioned published studies.⁵

The goal of the booster study is not only to help the subset of cancer patients who fail to mount an immune response after vaccination. Researchers are also theorizing that the booster dose may improve the duration of vaccine protection. 

It is currently unclear whether immunity after vaccination lasts as long for cancer patients as it does for healthy individuals, Dr Thakkar said. She and her colleagues are planning to measure antibody levels in the cancer patients from their prior study⁵ at 4 to 6 months after immunization. 

The study by Ehmsen et al showed that the number of patients with detectable antibodies dropped from 93% at 36 days after immunization to 86% at 3 months after immunization.²

The study by Dr Shroff and colleagues revealed a lag among the solid tumor patients, compared with the healthy control individuals, in the production of SARS-CoV-2-specific memory B cells and T cells.⁵ 

Unlike the healthy control individuals, cancer patients only generated B cells after the second immunization, and the level of T cells in patients after the second dose was similar to that in the control individuals after the first dose.

This finding indicates “there would be potential for immunity, but it was a delayed takeoff,” Dr Shroff said. As a result, she and her colleagues suggest that an additional dose may “elevate antibody responses in cancer patients” to those seen in healthy individuals after 2 doses. 

Questions Remain

Although studies have shown that patients with solid tumors have better responses to COVID-19 vaccination than do patients with hematologic malignancies, it still isn’t clear if patients with certain types of solid tumors fare worse than others, according to Dr Shroff.

Another unanswered question is whether certain chemotherapy regimens impair response to COVID-19 vaccination more than others.

“Unfortunately, our patient population was too small to really say,” Dr Shroff said. “As we hopefully continue to follow patients prospectively, we can get a better sense of those things because I think it is those nuances that are going to matter.” 

Another question is whether there is optimal timing for COVID-19 vaccination for patients who are receiving anticancer treatment. Although data are lacking, there is guidance that “rationally makes sense,” Dr. Shroff said, such as trying to get patients vaccinated before they start chemotherapy.¹ 

For those who are already on chemotherapy, she added, it is probably best to vaccinate about 1 week after the start of a cycle, giving patients’ immune cells time to recover.

“In the beginning, oncologists just wanted to get the vaccine to patients because we knew our patients were high risk and something was better than nothing,” Dr Shroff said. 

Now, she and others are trying to time the vaccinations a little more strategically, Dr Shroff said. She recommends that her patients get the additional booster because “there are no safety concerns, and if you didn’t already have a great response, we are hopefully boosting it.” 

Disclosures: Dr Shroff and Dr Thakkar reported having no relevant conflicts of interest.  

References

1. Corti C, Crimini E, Tarantino P, et al. SARS-CoV-2 vaccines for cancer patients: A call to action. Eur J Cancer. 2021;148:316-327. doi:10.1016/j.ejca.2021.01.04

2. Ehmsen S, Asmussen A, Jeppesen SS, et al. Antibody and T cell immune responses following mRNA COVID-19 vaccination in patients with cancer. Cancer Cell. 2021;39(8):1034-1036. doi: 10.1016/j.ccell.2021.07.016

3. Addeo A, Shah PK, Bordry N, et al. Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer. Cancer Cell. 2021; 39(8): 1091-1098. doi:10.1016/j.ccell.2021.06.009

4. Ligumsky H, Safadi E, Etan T, et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine among actively treated cancer patients. J Natl Cancer Inst. Published online August 28, 2021. https://doi.org/10.1093/jnci/djab174

5. Thakkar A, Gonzalez-Lugo JD, Goradia N, et al. Seroconversion rates following COVID-19 vaccination among patients with cancer. Cancer Cell. 2021;39(8):1081-1090. doi:10.1016/j.ccell.2021.06.002

6. Shroff RT, Chalasani P, Wei R, et al. Immune responses to COVID-19 mRNA vaccines in patients with solid tumors on active, immunosuppressive cancer therapy. medRxiv. 2021; doi:10.1101/2021.05.13.21257129

7. Coronavirus (COVID-19) update: FDA authorizes additional vaccine dose for certain immunocompromised individuals. News Release. US Food and Drug Administration. Published August 12, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised

8. A third dose of the COVID-19 vaccine recommended for some cancer patients with weakened immune systems: Latest information. Memorial Sloan Kettering Cancer Center. Published August 19, 2021. https://www.mskcc.org/coronavirus/third-dose-covid-19-vaccine-recommended-some-cancer-patients-weakened-immune-systems 

This article originally appeared on Cancer Therapy Advisor