People With Blood Cancer May Not Be Optimally Protected After mRNA COVID-19 Vaccination

Two new studies published in Blood suggest that the COVID-19 mRNA vaccine may have decreased efficacy in individuals with chronic lymphocytic leukemia (CLL) and multiple myeloma, two types of blood cancer. According to researchers, these studies could help determine the ideal time to vaccinate these populations.

Research suggests that the two-dose COVID-19 vaccine is less effective for people with CLL compared to healthy controls.

The first study reports that people with CLL had a markedly lower immune response to the mRNA COVID-19 vaccine at two doses than healthy subjects of the same age. Because clinical trials with these vaccines do not include patients with blood cancer who are at high risk for serious illness and complications from the virus, it is critical to measure the effectiveness of the vaccine in this population.

In this study of 167 patients with CLL, only four out of 10 (39.5%) had a positive antibody-mediated response to the vaccine; all healthy adults (controls), in comparison, produced an immune response.

Interestingly, the study revealed wide differences in immune response in patients with CLL depending on where they were in their cancer treatment process. For example, patients undergoing active cancer treatment had significantly lower response rates to the vaccine compared to those who completed treatment and were in remission, 16% versus 79%, respectively. Treatment-naïve patients (those whose disease is being viewed but not yet treated) had a response rate of 55.5%. Also, the response to the vaccine was markedly higher in people who had completed CLL treatment at least one year before vaccination, compared to those who were on treatment in the past year, 94% versus 50%, respectively.

“Overall, the response rate to the vaccine was significantly lower than what we see in the general population, which is most likely attributed to the presence of the cancer itself and certain CLL treatments,” said study lead author Yair Herishanu, MD, associate professor hematology and head of the CLL service at Tel Aviv Sourasky Medical Center in Israel. “It seems that if you are untreated, what we call ‘wait and see’ or do not have an active disease, you may benefit more from the vaccine. Patients who responded best were in remission, which makes sense because their immune systems have had a chance to recover. “

In addition to not receiving active CLL treatment, younger age, being female and having normal immunoglobin levels at the time of vaccination independently predicted a better response to the vaccine. In addition to poorer qualitative antibody responses to the vaccine, patients with CLL also had lower antibody titres, which tells us that, in addition to fewer patients who responded to the vaccine, the intensity of the response was also lower, Dr. Herishanu explained.

For the study, the researchers enrolled 167 patients with CLL and 53 healthy controls from December 2020 to February 2021. All participants received two doses of BNT162b2 messenger RNA (Pfizer) COVID-19 vaccine 21 days apart; this was the only vaccine used in Israel at the time of the study. The patients were an average of 71 years old and 67% were male. Fifty-eight patients (34.7%) were previously untreated; 75 (44.9%) received active therapy; 24 (14.4%) were previously treated and in complete or partial remission; and 10 (6%) relapsed. Antibody titres were also measured two weeks after the second dose. Patients had been followed for an average of 75 days since they received their first injection, and none of them had developed a COVID-19 infection. There were no significant differences in reported vaccine adverse reactions compared to the healthy population.

Researchers also looked at the immune response to the vaccine based on the CLL treatment patients received. They found similarly low response rates in patients receiving common targeted therapies, including Bruton’s tyrosine kinase (BTK) inhibitors (ibrutinib or acalabrutinib) or a combination of venetoclax with anti-CD20 antibodies such as rituximab. Notably, none of the patients who received anti-CD20 antibodies responded within 12 months of vaccination with COVID-19. Because only five patients received venetoclax monotherapy, Dr. Herishanu said they could not draw any conclusions about the impact on response.

People with CLL and other blood cancers are at high risk for serious illnesses and complications from COVID-19 infection, and although response rates are lower than ideal, vaccination against COVID-19 is highly recommended. The authors suggest that an additional booster dose of the vaccine may be required for patients with CLL who have completed therapy and previously failed to respond to the COVID-19 vaccine, although this should be investigated.

“Even though response rates were not optimal, patients with CLL should still receive the vaccine and, if appropriate, it may be better to do this before starting CLL treatment, although the disease itself may affect response,” said Dr. Herishanu. “Equally important is to continue to take precautions – wear a mask, avoid crowds, maintain a social distance and ensure close contacts are vaccinated against COVID-19.”

He and his team will continue to monitor these patients for 12 months to see how many, if any, develop a COVID-19 infection after vaccination. Because this study only assessed the antibody response, they also plan to monitor the cellular immune response to get a more complete picture of the extent to which patients are protected after vaccination.

The researchers note that the same trends can be expected with the other mRNA vaccine (Moderna).

Similar results in elderly patients with multiple myeloma

In a Blood Letter to the Editor also published online today, researchers report similar findings after the first dose of the same vaccine in elderly patients with multiple myeloma. Evangelos Terpos, MD, PhD, of the National and Kapodistrian University of Athens in Athens, Greece, and colleagues compared the results of 48 multiple myeloma patients and 104 healthy controls at Alexandra Hospital in Athens. The median age of all participants was 83. On day 22 after the first dose of the vaccine but before the second dose, antibody titres were measured and the median response was 20.6% neutralizing antibodies for the multiple myeloma population compared to 32.5% for the healthy controls.

At the time of the first dose, 35 (72.9%) patients were on antimyeloma therapy, four were in remission from prior therapy and were not receiving therapy at the time of vaccination, and nine had smoldering (precancerous) myeloma. Based on their findings, researchers suggest that antimyeloma therapy appears to negatively affect neutralizing antibody production after a single dose, although higher patient numbers are needed to further understand this effect. They also wrote that the administration of a second timely dose of vaccine is essential for elderly patients with multiple myeloma to develop an adequate antibody-based response.

For more information on COVID-19 vaccines for people with weakened immune systems, see the American Society of Hematology FAQs.