mRNA COVID-19 Vaccines May Decrease Efficacy in Lymphoid Malignancies

Jennifer Crombie, MD

Patients with lymphoid malignancies, especially those who have received recent anti-CD20 antibody therapy, have reduced humoral responses to the mRNA COVID-19 vaccines, and as such, should continue to take precautionary measures against COVID-19 infection irrespective of vaccination status, according to results from a study published in Blood Advances.^1,2

Results showed that among 6 patients who had received anti-CD20 antibody therapy within 12 months of vaccination, none mounted an antibody response to COVID-19 following both doses of the mRNA vaccines.

“Our findings suggest that patients with lymphoid cancers who have been vaccinated for COVID-19 should not assume they have immunity against the disease,” lead study author Jennifer Crombie, MD, a physician at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School, stated in a press release. “Patients should continue to be vigilant against becoming infected.”

Patients with lymphoid malignancies are not only at increased risk for developing COVID-19, but also at higher risk for experiencing poor outcomes. Additionally, in prior studies examining patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), recent anti-CD20 antibody therapy was associated with decreased humoral responses to the mRNA COVID-19 vaccines. Moreover, although patients on these studies who were treatment naïve were more likely to develop a humoral response to the vaccines, rates of humoral responses were still significantly lower in these patients compared with healthy controls.³

In the prospective study by Crombie and colleagues, investigators sought to evaluate serologic response following vaccination with both the Pfizer-BioNTech COVID-19 vaccine (previously referred to as BNT152b2; Comirnaty), as well as the mRNA-1273 vaccine, in patients with key lymphoid malignancies.

Patients with lymphoid malignancies who planned to receive 1 of the mRNA COVID-19 vaccines were eligible to enroll on the study. Patients who had received prior chimeric antigen receptor T-cell therapy or autologous stem cell transplant received their vaccine at least 3 months after completing the cellular therapy. All other patients were vaccinated based on their own preference or that of their provider.

Healthy controls for the study were adult healthcare workers from Brigham and Women’s Hospital who had no prior history of COVID-19 infection.

Investigators collected blood samples at 3 time points: before first dose of the vaccine, at the time of second dose, and then 28 days after second vaccine dose. Overall, 23 patients on the study received both dose of the vaccine and 21 completed all planned blood draws at the 3 time points.

Of the 23 patients enrolled, 14 had CLL (61%), 3 had diffuse large B-cell lymphoma (13%), 3 had mantle cell lymphoma (13%), 1 had follicular lymphoma (4%), 1 had marginal zone lymphoma (4%), and 1 had Hodgkin lymphoma (4%). The median age for patients enrolled on the study was 69 years (range, 30-82) compared with 24 years (range, 22-56) for the control group. Fifty-seven percent of participants in both groups were female and 70% of patients received the Pfizer-BioNTech vaccine.

Eleven patients were actively receiving treatment (48%), 6 had received prior treatment (26%), and 6 were treatment naïve (26%). Moreover, the median number of prior treatments received by patients was 1 (range, 0-3).

Fifteen patients had received prior treatment with an anti-CD20 antibody therapy (65%), 6 of whom had received this treatment within the previous 12 months and 9 of whom received it more than 12 months prior. Eight patients had received no prior anti-CD20 antibody therapy.

At baseline, no patients had detectable anti-nucleocapsid immunoglobulin G, which implied no prior infection with COVID-19. Additionally, although anti-spike immunoglobulin G titers were similar among patients with lymphoid malignancies and healthy volunteers at baseline (P = .66), the magnitude was lower at the time of the second vaccine dose (P = .0001) and 28 days after vaccination (P = .001) among the lymphoid malignancy cohort.

Additional data showed that 2 patients who underwent prior anti-CD20 antibody therapy within 12 months were able to develop anti-spike immunoglobulin G titers above the study’s predetermined threshold. However, both of those patients had also received the therapy more than 12 months before vaccination as well.

Moreover, all treatment-naïve patients enrolled on the study (n = 6) had developed anti-spike immunoglobulin G titers by the 28 days threshold after vaccination.

“Patients with lymphoid malignancies should not be assumed to be protected from vaccination and should remain maximally prudent to avoid infection,” study authors wrote. “Conversely, our findings suggest that humoral response can be seen following cytotoxic chemotherapy, in patients receiving anti-CD19–directed cellular therapy, and among patients who have not received prior therapy, even with CLL.”

References

1. Crombie JL, Sherman AC, Cheng C, et al. Activity of mRNA COVID-19 vaccines in patients with lymphoid malignancies. Blood Adv. 2021;5(16):3062-3065. doi:10.1182/bloodadvances.2021005328
2. Study sounds note of caution on effectiveness of COVID-19 vaccines for patients with lymphoid malignancies. News release. Dana-Farber Cancer Institute. August 23, 2021. Accessed August 24, 2021. https://bit.ly/38cpDHA
3. 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(23):3165-3173. doi:10.1182/blood.2021011568