Timing Important for COVID Vax in Patients With Blood Cancers

Nancy A. Melville

April 22, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

More evidence confirms that antibody-mediated response to COVID vaccination is impaired in patients with blood cancers, but one of the new studies also suggests that timing is important.

That study, conducted in patients with chronic lymphocytic leukemia (CLL), was published online April 16 in Blood. The researchers found that those patients whose responses were most impaired were undergoing active cancer treatment. The authors therefore suggest that vaccinations be administered before cancer therapy is initiated, if possible.

"In patients [with CLL] that are still untreated, or are planned to be treated shortly, a pre-therapy vaccination policy is highly recommended, though responses might also be affected by immunosuppression that accompanies the disease itself," say the authors.

In view of the impaired response, they also recommend that "vaccinated patients with CLL should continue to adhere to masking, social distancing, and vaccination of their close contacts should be strongly recommended."

Approached for comment, Mikkael Sekeres, MD, chief of the Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami Health System, Coral Gables, Florida, agreed that because of the reduced response rates, the timing of vaccination is important.

"If at all possible, patients should be vaccinated prior to initiating chemotherapy or immunotherapy or after treatment is complete," he told Medscape Medical News.

Sekeres recently co-authored an article that reported significant morbidity and mortality among people with hematologic malignancies who developed COVID-19. In light of their higher risk, it is essential to ensure that these patients are vaccinated, he said.

"We know from other studies that patients who have cancer of the bone marrow have much higher risks of serious outcomes from COVID-19, and even death, so if we can mitigate that even by 40% with the vaccine, I will take that," he said.

Sekeres strongly recommended that patients with blood diseases be vaccinated against COVID-19, and he underscored the importance of their taking other precautions.

"The additional advice that I give my patients is that because the efficacy of these vaccines is reduced in them, I can't be sure that the vaccine is going to be protective, so patients are urged to continue to wear masks, to avoid public settings, and continue to participate in the good public health hygiene that they've been doing for a year.

"I've also been telling them that in all likelihood, they will need a booster shot in the future ― as, frankly, most of us will," Sekeres commented.

Details of the CLL Study

The study involving patients with CLL was led by Yair Herishanu, MD, associate professor of hematology and head of the CLL service at the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

The researchers compared antibody responses to COVID vaccination that was administered from December 2020 through February 2021 among 167 patients with CLL and 53 healthy control persons.

All individuals received two doses of the Pfizer COVID-19 vaccine 21 days apart. (The authors comment that they would expect that results would be similar with the Moderna vaccine.)

Measurement of antibody titers 2 weeks after the second dose showed that among patients with CLL, only 39.5% demonstrated a positive antibody-mediated response to the vaccine, whereas all of the healthy control persons mounted a positive response (100%).

In a further analysis, 52 patients with CLL were compared with 52 age- and sex-matched healthy control persons. Response rates were 52% vs 100%, yielding an adjusted odds ratio of 0.010 (P < .001).

This low overall response rate to the vaccine in the CLL group is consistent with low response rates seen with other vaccines in this patient population, say the authors. Low response rates, ranging from 20% to 40%, have been reported with the pneumococcal conjugated vaccine (PCV13), the pneumococcal polysaccharide vaccine (PPSV23), and the HepB-CpG vaccine, as well as influenza A and B vaccines.

"The underlying causes for poor humoral response to vaccination in patients with CLL are multifactorial and attributed to disease-related immune dysregulation and therapy-related immunosuppression," they comment.

Among the patients with CLL, response rates to the COVID vaccine were highest among those whose disease was in clinical remission (79.2%). Athough this finding was encouraging, the response in these patients was still lower than the 100% response among healthy control persons.

"Patients who responded the best were in remission, which makes sense, because their immune system had a chance to recover," Herishanu said in a press statement.

Among the 34.7% of CLL patients who were treatment naive and who were undergoing a "watch and wait" management strategy, the response rate was 55%.

The lowest response rates occurred among patients undergoing active treatment ― only 16% of those taking a Bruton's tyrosine kinase inhibitor (ibrutinib or acalabrutinib) and 13.6% of those treated with a combination of venetoclax and anti-CD20 antibodies, such as rituximab.

Notably, among the patients who had been exposed to anti-CD20 antibodies within 12 months of being vaccinated, none showed a vaccine response.

Vaccine Responses Also Impaired in Multiple Myeloma

In a second study, published as a research letter in the same issue of Blood, researchers in Greece compared 48 patients with multiple myeloma with 104 healthy control persons who were vaccinated with the Pfizer COVID-10 vaccine.

The median age of the patients was 83 years. Antibody titers were measured on day 22 after the first of the two recommended doses of the vaccine.

Those results showed a median response rate of neutralizing antibodies of only 20.6% (range, 0 to 96.7%) among patients with multiple myeloma, compared with 32.5% (range, 5.2% to 97.3%) among the healthy control persons (P < .01).

Among the patients with multiple myeloma, only four (8.3%) developed antibody titers of at least 50%, corresponding to clinically relevant viral inhibition, compared with 21 health control persons (20.2%).

For the four patients with multiple myeloma who experienced a response, CLL was in remission, and the patients were not receiving anti-myeloma therapy. For all patients, uninvolved immunoglobulin levels were normal following treatment.

The authors, led by Evangelos Terpos, MD, PhD, of the National and Kapodistrian University of Athens, Athens, Greece, note that antibody response rates of 50% or more on day 21 after a single vaccine dose are low even among healthy individuals older than 65 years, underscoring the need for the second dose.

"Since our results indicate that elderly myeloma patients have a blunted antibody response after the first vaccine dose, they also suggest that the administration of a second timely vaccine dose is essential for this elderly subpopulation, with a malignant hematological disease that deregulates the immune homeostasis, to develop an adequate antibody-based immune response," the authors write.

The authors of the studies and Sekeres have disclosed no relevant financial relationships.

Blood. Published online April 16, 2021. Herishanu et al, Abstract; Terpos et al, Abstract

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