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Recent Publications of Interest for Chronic Lymphocytic Leukemia (CLL) Patients Related to COVID-19

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

I am introducing eight different research articles and commentaries on COVID-19 that are pertinent to the chronic lymphocytic community, and have informed my personal and institutional response to the demands and opportunities afforded by being one of the most vulnerable during a world-changing pandemic over the past weeks. You can just skim my highlights or use the numerous links to dive deeper.

Impaired Humoral Responses to COVID-19 Vaccination in Patients with Lymphoma Receiving B-Cell–Directed Therapies

This paper published in Blood on Sept 2, 2021, finds that after vaccination, no B cell lymphoma patients (that would include CLL) made the quick responding anti-SARS-CoV-2 IgM antibodies. The amount produced of the major workhorse antibody IgG varied, depending on the time since completing the latest anti-cancer therapy. Findings were that 88% responded by making antibodies if nine months or more had elapsed since completion of the last therapy. But only 11% of the patients in active treatment or whose treatment was less than nine months ago, responded with anti-COVID IgG. The level of IgA, the antibody found in mucous membranes such as the nose and respiratory tract, was higher in those who were more than nine months post-therapy compared to those who were less than three months out.

In summary, like other trials done in CLL patients, they conclude: “Our data suggest that SARS-CoV-2 vaccination at least 9 months from the last B-cell–directed treatment may result in improved antibody titers.”  With vaccinations occurring any sooner than that, the chances of a response are low.

The well-referenced editorial commentary in Blood can be read here: The Next Wave: Immunizing the Immunosuppressed.

Advice to Canadian Physicians Regarding Patients Asking for an Exemption From the COVID-19 Vaccination

This is directed towards Canadian physicians, specifically those in the province of Ontario, as part of FAQs on COVID-related issues. I thought it would be of interest to CLL patients in the US to see narrow exceptions recognized in the Canadian guidance to healthcare providers.

“Generally speaking, there are very few acceptable medical exemptions to the COVID-19 vaccination (e.g., an allergist/immunologist-confirmed severe allergy or anaphylactic reaction to a previous dose of a COVID-19 vaccine or to any of its components that cannot be mitigated; a diagnosed episode of myocarditis/pericarditis after receipt of an mRNA vaccine).”

That’s it if you want out of getting vaccinated in a setting where it’s mandated in Canada. Those are very good reasons to not risk the shots, but they are also extraordinarily rare.

In the US, I fear it is much easier to find a willing doctor who will cobble together an excuse with little to no scientific backing, making it easier for those who are hesitant about vaccines to avoid confronting the truth of the enormous benefits and the tiny risks.

Casirivimab-Imdevimab Treatment is Associated with Reduced Rates of Hospitalization Among High-Risk Patients with Mild to Moderate Coronavirus Disease

This is real-world data from Mayo, published in Lancet on August 20, 2021 on the use of casirivimab-imdevimab (REGEN-COV) in preventing disease progression in those with early COVID-19 infections.

Patients who received casirivimab-imdevimab had significantly lower all-cause hospitalization rates at day 14 (1.3% vs 3.3%), day 21 (1.3% vs 4.2%), and day 28 (1.6% vs 4.8).

Only 6.7% of the patients were immunocompromised, so data are too few to generalize to the CLL population. But it is encouraging to see that the antibodies worked well in the real-world setting.

Brii Biosciences Announces Positive Data from the Phase 3 ACTIV-2 Trial Evaluating Combination BRII-196 and BRII-198 in Non-Hospitalized COVID-19 Patients

The monoclonal antibody combination (BRII-196/BRII-198) therapy reduced the combined endpoint of hospitalizations and death by 78% over placebo in 837 COVID-19 outpatients who were at high risk of clinical progression. That would include the immunocompromised like us.

Here is the press release from August 24, 2021. As with all press releases, all we have are the topline findings, but they are very positive topline findings.

The more effective antibody choices we have that not only treat but prevent COVID-19 infections in vulnerable CLL patients the better. We hope to push Brii Biosciences to consider future prophylactic trials as done by Regeneron, Astra Zeneca, and Adagio.

“Inescapable” COVID-19 Antibody Discovery – Neutralizes All Known SARS-CoV-2 Strains

One nightmare concern is that the SARS-CoV-2 virus will continue to mutate and eventually evade protection from all vaccines and monoclonal antibodies.

Deep analysis of the viral structure and its binding could result in a smarter antibody that is more broadly active and less likely to become ineffective.

A study published in Nature July 14, 2021, suggests that the researchers may have just such an antibody, and early pre-clinical studies suggest the virus is unable to escape. “One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge.” Sarbecovirus is the viral subgenus that includes the viruses that cause COVID-19.

The Nature article can be found here: SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape.

While there is a long way to go from hamster studies to getting a drug approved in humans, this is a potentially huge discovery. My fingers are crossed!

Study Demonstrates Saliva Can Spread Novel Coronavirus

No big surprise here. The SARS-CoV-2 virus is found in saliva, can reproduce in the mouth, and infect other cells. So besides not shaking hands, we also can’t kiss. Sorry!

This is from the NIH Director’s Blog back in April 2021.

Protecting the Immune-Compromised Keeps Everyone Safe

This very personal commentary from Wired in August 2021 where the author reminds us: “Researchers already knew flu viruses could mutate substantially in immune-compromised people, and a host of recent case studies have shown that COVID-19 infections can persist for months in some immune-compromised people—even shedding virus for up to two months”.

Protecting us protects the world. It’s a good read and helps frame our vulnerabilities and constricted circumstances in this fast-changing pandemic world.

Stay strong. We are all in this together.

Brian Koffman MDCM (retired) MS Ed

Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.