COVID-19 vaccination appears less effective among patients with active leukemia, myeloma
Patients with active chronic lymphocytic leukemia or multiple myeloma mounted lower antibody responses to mRNA COVID-19 vaccination than healthy individuals, according to data from two reports published in Blood.
The findings suggested the lower antibody response may be a result of both the cancer and its treatments.
In one study, Yair Herishanu, MD, associate professor in hematology and head of the CLL service at Tel Aviv Sourasky Medical Center in Israel, and colleagues found that individuals with CLL had a substantially lower rate of immune response to the two-dose BNT162b2 mRNA COVID-19 vaccine (Pfizer, BioNTech) compared with healthy age-matched controls.
“Patients with CLL are predisposed to develop infections due to inherent immune defects related to their primary disease and as a result of therapy. The mechanisms underlying the immunodeficiency in CLL may also reduce response to vaccines,” Herishanu told Healio. “We found that the antibody response to BNT162b2 mRNA COVID-19 vaccine in patients with CLL is markedly impaired and affected by disease activity and treatment.”
In a research letter, Evangelos Terpos, MD, PhD, professor of hematology in the department of clinical therapeutics at National and Kapodistrian University of Athens in Greece, and colleagues reported that older patients with multiple myeloma also appeared to have less robust responses to the BNT162b2 mRNA COVID-19 vaccine.
“Our knowledge from vaccines against other viruses have suggested that the response of [patients with myeloma] is lower compared with healthy individuals,” Terpos told Healio. “The key message of our study is that the first dose of the BNT162b2 mRNA COVID-19 vaccine produces low levels of neutralizing antibody response among elderly patients with multiple myeloma compared with controls of similar age.
“Responders to the first vaccine dose seem to be patients who are away of treatment with normal noninvolved immunoglobulins,” Terpos added. “More data are needed to know the results of the second dose as well as the results among younger patients with multiple myeloma. However, it is totally necessary for these patients to receive the second dose of the vaccine.”
Herishanu and colleagues compared antibody-mediated response to the BNT162b2 mRNA COVID-19 vaccine administered between December and February to 167 patients (median age, 71 years; 67% men) with CLL vs. 52 healthy controls.
Among patients with CLL, 44.9% were on active treatment, 34.7% were treatment naive, 14.4% were previously treated and in complete or partial remission, and 6% were in relapse.
The proportion of patients acquiring anti-COVID-19 antibodies — with an antibody titer of 0.8 U/mL or higher, measured using the Elecsys Anti-SARS-CoV-2S assay (Roche Diagnostics) 2 to 3 weeks after the second dose, considered as positive — served as the primary endpoint.
Median follow-up was 75 days after the first vaccine dose. No patients developed COVID-19 infection during the study period and no substantial differences in adverse events associated with the vaccine occurred between the groups.
According to study results, only 39.5% of patients with CLL had a positive antibody-mediated response to the vaccine. When comparing 52 matched patients with CLL with the control group, results showed the former group was significantly less likely to mount a response to vaccination (52% vs. 100%; OR = 0.01; 95% CI, 0.001-0.162).
Researchers additionally observed a substantial difference in response rates to the vaccine according to treatment status. Patients who completed treatment for CLL and were in remission showed a 79.2% response rate to vaccination, with higher rates among those who had completed CLL treatment a year or more before receiving the vaccine than among patients still on active treatment within the previous year (94.1% vs. 50%, P = .04).
Further, no patients treated with anti-CD20 antibodies within the last year responded vs. 45.5% of those who received anti-CD20 therapy at least a year prior to vaccination.
Patients with CLL on a watch-and-wait protocol achieved a 55.5% response to the vaccine, whereas those on active treatment only showed a 16% response rate.
“Vaccinated patients with CLL should continue to adhere to masking, social distancing and vaccination of their close contacts should be strongly recommended,” Herishanu said.
Researchers are planning longer follow-up to assess the infection rate, disease severity and the usefulness of a booster dose among patients with CLL who have been vaccinated, he added.
“We will continue to study the cellular response to the vaccine and for how long the immune response to the vaccine is maintained,” he said.
Terpos and colleagues compared outcomes among 48 patients (median age, 83 years; men, n = 29) with multiple myeloma and 104 healthy controls (median age, 83 years; men, n = 57) who received the COVID-19 vaccine during the same period.
Researchers used the cPass SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript) to measure antibody titers 22 days after the first dose of the vaccine, but before the second dose, with a neutralizing antibody titer of at least 30% defining positivity.
Approximately 73% of patients were receiving treatment for multiple myeloma at the time of their first vaccine dose, whereas four patients were in remission and not actively receiving treatment. Nine patients had smoldering myeloma.
Results showed a median neutralization antibody titer of 20.6% among patients with multiple myeloma compared with 32.5% among healthy controls (P < .01). Achievement of at least a 30% neutralizing antibody titer by day 22 occurred among 25% of patients with myeloma compared with 54.8% of controls.
After a single dose of the vaccine, antimyeloma therapy appeared to negatively affect the neutralizing antibody production, although study of more patients is needed to evaluate the effects of specific antimyeloma regimens on the immune responses of anti-COVID-19 vaccination, the researchers noted.
“We are continuing to evaluate the efficacy of both BNT162b2 vaccine doses among all [patients with multiple myeloma,] irrespective of their age and treatment given,” Terpos said. “We are also assessing the efficacy of the Moderna and AstraZeneca vaccines among both patients with multiple myeloma and other hematologic malignancies.”
For more information:
Yair Herishanu, MD, can be reached at Department of Hematology, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel-Aviv, Israel, 64239; email: firstname.lastname@example.org.
Evangelos Terpos, MD, can be reached at Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, 80 Vas. Sofias Ave., 11528, Athens, Greece; email: email@example.com.