COVID-19 vaccination appears less effective among patients with active leukemia, myeloma
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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.”
CLL
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.
Multiple myeloma
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.”
References:
Herishanu Y, et al. Blood. 2021;doi:10.1182/blood.2021011568.
Terpos E, et al. Blood. 2021;doi:10.1182/blood.2021011904.
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: yairh@tasmc.health.gov.il.
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: eterpos@med.uoa.gr.
Perspective
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Gwen Nichols, MD
These findings are in line with what we anticipated for patients with chronic lymphocytic leukemia or multiple myeloma. We know patients who have undergone bone marrow transplant and those who are on anti-B-cell therapies may not have a good antibody response to other vaccines, and we are aware that patients on these therapies often need quite a bit of time off therapy before they can recover enough to respond to vaccination — or at least respond in the best way we currently evalute response, which is by determining whether they make an antibody.
People with cancer were largely excluded from COVID-19 vaccine trials. However, this highlights why we should have been doing trials of immune-suppressed patients in concert with rather than after the vaccine rollout. There should have been more effort to understand the impact on this population given this outcome was so likely.
The Leukemia & Lymphoma Society (LLS) created a national patient registry in honor of Michael Garil and we are using the registry to improve understanding of how the novel coronavirus and COVID-19 vaccination affect people with blood cancer. We are assessing the first large group of patients for whom we have antibody responses after completing vaccination. We intend to look at differences in therapies, timing and disease state. With all of the caveats that go along with a registry that relies on patient-reported outcomes, patients are incredibly motivated to be part of this and improve our understanding, precisely because of the reports that are coming out about a potential lack of ability to respond normally to vaccination.
Survey results released by LLS in March showed nearly one-third of people diagnosed with blood cancers indicated they either were unlikely to get a COVID-19 vaccine or were unsure about doing so. The most common reason respondents expressed for their vaccine hesitancy was a lack of scientific evidence that it was safe, and we can provide that now. The safety profile from the first 3,500 patients in our registry showed most of the adverse effects in the blood cancer population were the same as we hear from our family and friends, such as sore arms, injection site pain or fatigue. Our data show nothing that hasn’t been reported in the general population.
Importantly, we still don’t know what it means if someone doesn’t make antibody. It is clear there are other parts of the immune system that can compensate. Otherwise, everyone who takes an anti-CD20 antibody therapy or a Bruton tyrosine kinase inhibitor would have frequent and serious viral infections. That is not the case, so we know the adaptive part of the immune system plays a role in fighting viruses.
As part of the registry, we intend to identify patients who didn’t make full antibody response, match them with patients who did and give a special test that looks at T-cell activation against the vaccine. Even if the T cells tried to respond to the vaccine, we still don’t know if that is protective. However, we have to learn, so there is a lot of science still to be done.
In the meantime, it is critical for providers to encourage their patients with blood cancer — who may not have full immunity — to continue to take all necessary precautions, such as hand-washing, wearing face masks and social distancing, and to make sure the people around their patients get vaccinated. That will go a long way to help people with blood cancer, who no matter what they do may not have the same ability to be protected.
I also hope physicians will encourage their patients to join our registry, available online at www.lls.org/registry. There are some disease types — particularly myeloid malignancies, such as chronic myeloid leukemia and other myeloproliferative neoplasms — for which we do not have enough information to understand their risks.
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