by Dr. C.H. Weaver M.D. 7/2021

Because clinical trials of COVID-19 vaccines did not include patients with blood cancers and patients with these cancers are at high risk of severe illness and complications from the virus, there is great interest in understanding the effectiveness of vaccines in these groups of patients. Two studies published in the medical journal Blood suggest that the mRNA COVID-19 vaccine has reduced effectiveness in individuals with chronic lymphocytic leukemia (CLL) and multiple myeloma, two types of blood cancer - this information is applicable to individuals with lymphoma as well. Overall, the response rate to the vaccine was significantly less than reported for the general population and this is most likely attributed to the presence of cancer itself and certain treatments that suppress the immune system.1,2

Researchers compared 167 patients with CLL to 53 healthy individuals who received two doses of BNT162b2 messenger RNA (Pfizer) COVID-19 vaccine 21 days apart between December 2020 through February 2021. Antibody titers were also measured two weeks after the second dose. The researchers report that people with CLL had significantly lower immune response rates to the two-dose mRNA COVID-19 vaccine compared to healthy individuals of the same age. Only 40% of patients had a positive antibody-mediated response to the vaccine. There were however wide variations in immune response based on where patients were in their cancer treatment.

  • Patients undergoing active cancer treatment had significantly lower response rates to the vaccine when compared with people who had completed treatment and were in remission, 16% vs 79% respectively.
  • Treatment naïve patients had a 55.5% response rate and response to the vaccine was higher in people who completed CLL treatment at least a year before vaccination compared with those who were still in treatment within the last year, 94% vs 50%, respectively.
  • Low response rates among patients who were receiving treatment with Bruton’s tyrosine kinase (BTK) inhibitors (ibrutinib or acalabrutinib) or a combination of venetoclax with anti-CD20 antibodies such as rituximab were reported. No patients who received anti-CD20 antibodies within 12 months of COVID-19 vaccination responded.
  • Patients with CLL also had lower antibody titers, which tells us that, in addition to fewer patients responding to the vaccine, the intensity of the response was also lower.

Although the evaluation was performed in individuals receiving the BNT162b2 messenger RNA Pfizer vaccine there is no reason to believe the same trends would not be expected with the Moderna mRNA vaccine. The results of the study are generalizable to patients with non-hodgkin lymphoma as well which is a similar B cell cancer managed with the same immunosuppressive medications.

Response to COVID-19 Vaccines in Multiple Myeloma Can Be Suboptimal

Patients with multiple myeloma appear to have a widely variable response to COVID-19 vaccines, according to a study published in Cancer Cell. Mount Sinai researchers found that multiple myeloma patients mount variable and sometimes suboptimal responses after receiving the Pfizer-BioNTech or Moderna COVID-19 vaccines. Almost 16 percent of these patients developed no detectible antibodies after both vaccine doses.

Researchers analyzed the antibody levels of 320 multiple myeloma patients, 260 of whom received two doses of COVID-19 vaccinations and found that 15.8 percent had undetectable antibodies. The multiple myeloma patients who had had COVID-19 before vaccination showed immune responses that were 10 times higher than those who had not.

Overall, 84% of fully vaccinated patients had measurable IgG antibody levels of varying magnitude, however 16% of patients had undetectable IgG antibody levels after vaccination. 

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More than half (58.5%) of patients who had undetectable IgG antibody levels were on active treatment with anti-CD38 antibody-containing therapy at the time of vaccination, 31.7% were on anti-BCMA bispecific antibody therapy and 9.8% underwent anti-BCMA chimeric antigen receptor T-cell therapy more than 3 months before vaccination. Research into strategies to boost immune responses, such as third/booster vaccines or passive antibody infusions, is urgently needed.5

Can Blood Cancer Patients with Low Antibody Levels Fight off COVID-19 with T Cells?

Antibodies aren’t the only immune cells needed to fight off COVID-19 — T cells appear equally important. Researchers have found that blood cancer patients with COVID-19 who had higher CD8 T cells, many of whom had depleted antibodies from cancer treatments, were more than three times likelier to survive than patients with lower levels of CD8 T cells suggesting that T cells play an important role.

This research suggests that T cells may compensate for B cell and antibody responses, which are diminished in many cancer patients because of chemo-immunotherapy. Additionally, because the current COVID-19 mRNA vaccinations induce both antibody and T cell responses, the findings suggest that vaccination of blood cancer patients could provide protection through T cell immunity, despite the absence of antibodies.

Researchers at Memorial Sloan Kettering and Penn Medicine performed Immune profiling of patients with and without cancer. They found that patients treated with anti-CD20 antibodies had decreased B cells and antibodies compared to patients with solid cancers and patients without cancer. Analyses among patients with blood cancers, including patients treated with chemotherapy and anti-CD20 antibodies, individuals with higher CD8 T cell counts had a 3.6 fold greater likelihood of survival compared to those with lower T cell counts. Thus, the authors concluded, CD8 T cells may influence recovery from COVID-19 when B cells and antibodies are deficient.

People with CLL and other blood cancers remain at high risk for severe illness with COVID-19 infection. Although vaccine response rates are low, vaccination against COVID-19 remains strongly recommended. Optimal vaccine timing would be before beginning treatment although this is obviously not an option for all patients. An additional booster dose of the vaccine might also be beneficial after completion of therapy, although this will need to be studied. It remains important for individuals with CLL, myeloma and lymphomas to continue to take precautions which include wearing a mask, avoiding crowds, keeping a social distance and being sure close contacts get vaccinated against COVID-19.

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References:

  1. Efficacy of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Chronic Lymphocytic Leukemia
  2. Low Neutralizing Antibody Responses Against SARS-CoV-2 in Elderly Myeloma Patients After the First BNT162b2 Vaccine Dose
  3. https://www.nature.com/articles/s41591-021-01386-7.epdf?
  4. https://www.mountsinai.org/about/newsroom/2021/response-to-covid19-vaccines-varies-widely-in-blood-cancer-patients
  5. Van Oekelen O, et al. Cancer Cell. 2021;doi:10.1016/j.ccell.2021.06.014.