Cancer Treatment Today

First, the risk of Covid infection in CLL patients is not greater than that of the general population. White the database on risk of COVID infection in immunodeficient patient is only now beginning to be expanded, preliminary evidence appears to show that immunodeficient patients are not at greater risk of either contacting or dying from COVID. This makes sense because of what we know about the pathogenesis of this infection, and its effects on the body being mediated primarily through cytokine responses. As such, and immunodeficient patient might actually do better than other patients. A recent New England Journal article showed that there is no excess mortality and rheumatologic patients and immune suppressive therapy.
• A systematic review and meta-analysis by Gao also showed that patients with immunosuppression in 2019 seem to be few in relation to totalnumbers and presented a favorable outcome as a compared to other comorbidities. Meta-analysis itself showed no significant difference between the risk of severe COVID 19 disease and immunosuppression immunodeficiency
• In as far as the risk of Covid after a cancer-free stat had been achieved, researchers from the University of Birmingham and the University of Oxford observed 800 patients enrolled in the UK Coronavirus Cancer Monitoring Project, which provides real-time reports to frontline clinicians about the effects of COVID-19 on patients who have cancer. The primary end point of the prospective study, conducted from Mar 18 to Apr 26, was all-cause mortality or discharge from the hospital. The researchers were particularly interested in how patients receiving anticancer treatment have been affected.
Of the 800 patients studied, 412 (52%) had mild COVID-19 illness, 96 (12%) did not require hospitalization, 315 (39%) required oxygen, and 53 (7%) received intensive care. A total of 226 patients (28%) died, with the vast majority (211, 93%) dying from COVID-19. Multivariable logistic regression analysis showed that risk of death was significantly associated with advancing patient age (OR, 9.42; 95% CI, 6.56 to 10.02), being male (OR, 1.67; 95% CI, 1.19 to 2.34), and the presence of other comorbidities such as hypertension (OR, 1.95; 95% CI, 1.36 to 2.80) and cardiovascular disease (OR, 2.32; 95% CI, 1.47 to 3.64).
A univariate analysis found that, compared with patients who had not received chemotherapy within 4 weeks of testing positive for COVID-19, those who had received recent chemotherapy did not have a higher death rate (29% with recent chemotherapy vs 27% without recent chemotherapy). A multivariate analysis of 281 of patients who had received recent chemotherapy, after adjusting for age, gender, and comorbidities, found that chemotherapy had no significant effect on mortality (OR, 1.18; 95% CI, 0.81 to 1.72).
Multivariate analysis also found that, compared with patients who were not on these therapies, patients on immunotherapy (OR, 0.59; 0.27 to 1.27), hormonal therapy (OR, 0.90; 95% CI, 0.49 to 1.68), radiotherapy (OR, 0.65; 95% CI, 0.36 to 1.18), or targeted therapies (OR, 0.83; 95% CI, 0.45 to 1.54) were not at any additional risk of death.
The authors of the study said their takeaway from these findings is that anticancer treatments should not necessarily be withheld in COVID-19 patients.
“In patients presenting to UK National Health Service trusts or cancer centres, our data are strongly indicative that cancer plus COVID-19 mortality is principally driven by advancing age and the presence of other non-cancer comorbidities,” they wrote. “We concluded that withholding effective cancer treatments from many cancer patients during the pandemic runs the very real risk of increasing cancer morbidity and mortality, perhaps much more so than COVID-19 itself.” (https://www.cidrap.umn.edu/news-perspective/2020/05/studies-highlight-covid-19-impact-cancer-patients).
Secondly, the effectiveness of vaccines for Covid in CLL is much less than expected, making the risk-benefit ration insufficient. B cells are critical to fighting COVID-19. These are the immune cells that can neutralize the virus and help produce antibodies. People with CLL are at an increased risk of not responding to Covid vaccination because B cells are the most affected by this specific type of blood cancer.
A 2021 study in Blood found that people with CLL who were vaccinated with Pfizer’s mRNA COVID-19 vaccine had an antibody response rate of 39.5 percent. In generally healthy adults, this rate is around 90 percent.
Individual response rates varied among people with CLL based on their disease progression and treatment. Response rates in different groups of people with CLL included:
• 79.2 percent response rate in people in clinical remission from CLL
• 55.2 percent response rate in people with CLL who hadn’t yet received treatment
• 16 percent in people with CLL who were undergoing treatment at the time of COVID vaccination
While response rates were generally low in people with CLL receiving treatment at the time of vaccination, these rates were further impacted by the type of treatment.
People treated with Bruton’s tyrosine kinase (BTK) inhibitors had a 16 percent response rate to the vaccine, while those treated with venetoclax ± anti-CD20 antibody had just a 13.6 percent response rate. No one who was treated with anti-CD20 antibodies in the year before COVID-19 vaccination had any immune response, according to the study.
There were other factors that affected how well people with CLL responded to the vaccine, too. Researchers found that the people with CLL who had the best responses to the vaccine:
• were younger in age
• were female
• weren’t receiving active treatment for CLL
• had immunoglobulin G levels of 550 mg/dL or higher
• had immunoglobulin M levels of 40 mg/dL or higher

About one in four blood cancer patients fail to produce detectable antibodies after COVID-19 vaccination, according to a new study from The Leukemia & Lymphoma Society (LLS) that was published in the journal Cancer Cell.
A paper in Leukemia found that only half of vaccinated patients with CLL develop detectable anti-SARS-CoV-2 S1/S2 antibodies. They conclude: “These striking findings suggest that vaccination in patients with CLL may not confer the efficacy that we expect in the general population, particularly in patients receiving CLL-directed therapy. ….. These data support conducting prospective clinical studies of vaccine efficacy in patients with CLL and other immunocompromising conditions. While we await establishment of herd immunity, specific guidance for patients with CLL are warranted as the current Center for Disease Control and Prevention recommendations regarding relaxed personal protective equipment use when around other vaccinated people may not apply to this population. Without consistent antibody responses, patients with CLL should continue to exercise extreme caution following vaccination until further data on clinical efficacy are available.
Leukemia and Lymphoma society says: “LLS encourages anyone with a current or past blood cancer diagnosis who has already been vaccinated to talk with their health care team about whether and when they should receive another vaccine dose. Those who are not vaccinated should consult with their health care team about starting the vaccination series as soon as possible.”

The American Society of Hematology says: “While the safety of vaccine for each patient should be assessed on a case-by-case basis depending on its reported side effects and patient’s comorbidities, we would in general recommend it for patients with a CLL/SLL diagnosis. “

Bibliography:
Gao Y, Chen Y, Liu M, Shi S, Tian J. Impacts of immunosuppression and immunodeficiency on COVID-19: A systematic review and meta-analysis. J Infect. 2020;81(2):e93-e95. doi:10.1016/j.jinf.2020.05.017

Haberman R, Axelrad J, Chen A, et al. Covid-19 in immune-mediated inflammatory diseases — case series from New York. N Engl J Med 2020;383:85-88.
Yair Herishanu, etal, Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia. Blood (2021) 137 (23): 3165–3173.
Roeker, L.E., Knorr, D.A., Thompson, M.C. et al. COVID-19 vaccine efficacy in patients with chronic lymphocytic leukemia. Leukemia 35, 2703–2705 (2021).
https://lls.org/who-we-are/covid-19-vaccines-faq-patients-and-caregivers, Accessed 9/12/2021

https://www.hematology.org/covid-19/covid-19-and-cll

Accessed 9/12/2021