It has been more than a year and a half since the World Health Organization first declared COVID-19 a pandemic disease.1 Remarkably, during that time several mRNA vaccines have been approved for use in the United States, each with a good safety profile and high efficacy in preventing infection by the SARS-CoV-2 virus.1
Although doctors knew early in the pandemic that immunocompromised patients were at higher risk of severe disease and death from COVID-19, patients with impaired immune systems were excluded from participating in the initial vaccine clinical trials.1 Recent analyses of real-world patients who received COVID-19 vaccination have shown that some immunocompromised patients, including those with chronic lymphocytic leukemia (CLL), are less likely to form antibodies that would protect them from COVID-19.1-4
In a recent clinical trial, investigators sought to evaluate the safety and ability of 2 doses of Pfizer-BioNTech’s mRNA vaccine to promote the production of protective antibodies against SARS-CoV-2 in immunocompromised patients.1 Five groups of adult patients were accepted in the study, including those with a chronically weakened immune system, and those whose immune systems had been compromised by 1 of the following: HIV infection; receipt of a stem-cell transplant or chimeric antigen receptor T-cell (CAR-T) therapy; solid organ transplant; or CLL.1 For comparison, a group of healthy individuals who were not immunocompromised were also included.1
Of the 539 subjects included in this study, 97.4% received both doses of the vaccine.1 The 14 subjects who did not receive a second dose included 9 who were diagnosed with COVID-19 between the 2 doses, and 5 who had side effects that prevented completion of the vaccination series.1 Side effects in the study were similar between the immunocompromised patients and healthy subjects and were generally mild in severity.1 However, 1 patient who had previously received a stem-cell transplant and CAR-T therapy had a serious reaction 4 days after their first vaccine dose, and subsequently died of lung failure 2 months later.1
Immunocompromised patients were less likely to form an effective antibody response after full vaccination compared with the healthy subjects. Whereas all healthy subjects (100%) showed antibodies to SARS-CoV-2, efficacy was only approximately 72% in immunocompromised patients.1 Vaccination was least effective in patients who had received a solid organ transplant (about 43% showed antibodies) and most effective in patients with HIV (approximately 98% produced antibodies).1
Looking at patients with CLL, approximately 63% formed antibodies after 2 vaccine doses, although the likelihood of having an effective immune response varied depending on whether they were receiving current CLL treatment.1 Specifically, only approximately 27% of patients who were receiving ongoing treatment with ibrutinib developed antibodies after vaccination, whereas vaccines were approximately 56% effective in patients who were no longer being treated with ibrutinib.1 For patients undergoing watchful waiting, or who were off long-term chemoimmunotherapy, COVID-19 vaccination was more than 80% effective.1
The preliminary results from this study suggest that 2-dose COVID-19 vaccination is generally safe for immunocompromised patients, although the efficacy is substantially lower than in healthy individuals.1 Specific vaccination strategies, such as adding a third booster dose,* or pausing ongoing therapies may be required to adequately protect these patients.1
*Note that as of September 2021, the US Centers for Disease Control and Prevention has recommended a third dose booster for immunocompromised patients who have already received 2 doses of the Pfizer-BioNTech COVID-19 vaccine.5,6
References
- Bergman P, Blennow O, Hansson L, et al. Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial. medRxiv. Published September 14, 2021. www.medrxiv.org/content/10.1101/2021.09.07.21263206v2. Accessed October 18, 2021.
- Herishanu Y, Avivi I, Aharon A, et al. Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia. Blood. 2021;137:3165-3173.
- Diefenbach C, Caro J, Koide A, et al. Impaired humoral immunity to SARS-CoV-2 vaccination in non-hodgkin lymphoma and CLL patients. medRxiv. Published June 3, 2021. www.medrxiv.org/content/10.1101/2021.06.02.21257804v1. Accessed October 18, 2021.
- Herzog Tzarfati K, Gutwein O, Apel A, et al. BNT162b2 COVID-19 vaccine is significantly less effective in patients with hematologic malignancies. Am J Hematol. 2021;96:1195-1203.
- Centers for Disease Control and Prevention. Who is eligible for a COVID-19 vaccine booster shot? Updated October 7, 2021. www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html. Accessed September 27, 2021.
- Centers for Disease Control and Prevention. People with certain medical conditions. Updated October 14, 2021. www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Accessed October 18, 2021.