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UPDATE: Getting Personal with CLL / SLL, COVID-19, Vaccines, Monoclonal Antibodies, Anti-Virals, Omicron, and Living with Uncertainty

In science and medicine, information is constantly changing and may become out-of-date as new data emerge.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.

Ten days later and a major rewrite of this article. Viruses never sleep.

As an immunocompromised chronic lymphocytic leukemia patient, I wanted certainty that I could reengage with the world without playing Russian roulette with a virus. It seemed tantalizingly close to becoming my reality. Now, it seems it might be less sure with the emergence of the Omicron COVID-19 strain.

I hope readers might find value in me sharing my take on the nature and extent of this uncertainty, and the coping strategies that have helped me over 16 years of living well with CLL. Let’s first take stock of where we are today, knowing that it could all be different tomorrow.

We have long known that staying locked up at home and sheltering in place is very safe, and is probably the best way to keep us from catching COVID-19. But the growing question has been, is it possible to begin doing more and still be okay?


We know that well-fitting masks, especially N95s, and the other protective efforts outlined by the CDC provide high levels of safety against catching any COVID-19 variant.

With Omicron being so contagious, N95 or KN95 masks should now be considered mandatory when leaving home. Forget that designer cloth mask. Omicron laughs at it.

So, is there any way of resuming travel, eating indoors, partying with friends and family, or a million other things that were so normal back in 2019 in what now seems like an unimaginably different life?

Let’s look.


We know vaccines greatly help to protect us when we are moving around in the larger world. But we never could assume that they provided reliable, robust protection in people with CLL / SLL, even before the appearance of the Omicron variant.

We now know that those with normal immunity do have significant protection against severe infection from Omicron with a third dose of either the Pfizer or Moderna vaccine.

We know that the third dose of an mRNA vaccine helps some of those with CLL / SLL (but not the majority) to develop significant antibody levels. We know nothing about the benefits of that third dose in CLL / SLL patients for preventing Omicron. Will a fourth dose of an mRNA COVID-19 vaccine be the ticket? No one knows. Zero data.

We have more recent research that suggests that the strength of our cellular immunity (T cells that recognize the virus) can’t be predicted based on our antibody response to the vaccine and is suboptimal.


We know that all the authorized anti-SARS-CoV-2 monoclonal antibodies (mAbs), when used both for treatment of those infected and for pre and post-exposure prophylaxis, provided excellent protection against all SARS-CoV-2 variants up to and including the Delta variant. But Delta has been upstaged by Omicron as the major troublemaker at the time of this revision and there is a different story emerging.

We now know that the two main mAbs used in the USA (Regen-Cov and Lilly’s bamlanivimab and etesevimab [bam/ete]) offer little if any protection against Omicron. GSK’s sotrovimab remains very active but is in desperately short supply.

Some good news: We know that Brii Boiscience’s experimental mAb combination, amubarvimab/romlusevimab, is working its way towards EUA for outpatient use in those with mild or moderate COVID-19 at high risk for progression and appears to retain its activity against Omicron.

We know that one trial for (PrEP) with Regen-Cov has stopped enrollment and that ADAGIO (ADG20), who was in the process of developing a promising new mAb, is now reassessing their best path forward for their PrEP clinical trial plans due to the rise of Omicron and their antibodies’ lack of efficacy.

All is not lost. Regeneron and the other manufacturers have extensive libraries of antibodies to help stay ahead, or at least even with this fast-moving virus.

Some more good news: EVUSHELD, already authorized for pre-exposure prophylaxis (PrEP) remains active against Omicron based on its neutralizing effects against the virus in lab studies. There are no clinical data yet and there is an unexplained disconnect between poor results of EVUSHELD on tests on a pseudovirus versus good results on the real virus.


Antivirals are coming, led by Pfizer’s new oral pill Paxlovid that was recently authorized for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adult and pediatric patients age 12 years and older weighing at least 40 kg, with positive SARS-CoV-2 test, who are at high risk for progressing to severe COVID-19, including hospitalization or death. CLL patients would be included. We know that Paxlovid is extremely effective in preventing severe COVID-19. However, we don’t know how well it will work in people with CLL / SLL, or how well it will work against Omicron. But we have every reason to believe that it will work very well in high-risk populations like those with blood cancers, regardless of the variant. Mutations in the spike protein may render the monoclonal antibodies impotent, but they should have no effect on medications such as Paxlovid that interfere with replication.

Paxlovid has potentially dangerous drug-to-drug interactions with many of the treatments commonly used for CLL, so that is very likely going to be another critical consideration in managing care. But with the help of our medical teams, that should be a bridge that can be crossed. Many CLL medications will need to be held while on Paxlovid, but in most clinical circumstances, that is doable.

Merck’s oral med, molnupiravir, was also recently authorized for emergency use (Merck and Ridgeback’s Molnupiravir Receives U.S. FDA Emergency Use Authorization for the Treatment of High-Risk Adults With Mild to Moderate COVID-19) but its efficacy is a similar clinical setting as Paxlovid and is likely in the high 30% to up to 50% compared to almost 90% for Paxlovid in preventing progression.

Today the difference is moot. While both manufacturers are committed to having an adequate supply of their life-saving medications, neither are anywhere to be found at the time of writing. Oral antivirals are easier to make and thus ramp up production compared to the antibodies, so this should be a fixable problem if the federal and state governments can get their acts together. That may be asking a lot.

Meanwhile, while waiting for the oral medications to make it to a pharmacy near you, there is an excellent option if one tests positive for COVID-19 and has mild to moderate disease and is in the first few days post-diagnosis with a high risk to progress. IV remdesivir, an already fully FDA approved intravenous antiviral, given outpatient as three short infusions over three consecutive days lowered progression risk by 87%. This is as published in the prestigious New England Journal of Medicine: Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. And again, though not studied against Omicron, as is the case with the other antivirals, there is no reason to believe it won’t work on all variants.

Here is a nice summary from the NIH of what is known about the variants of concern (VOC) as they relate to the sensitivity of vaccines, monoclonal antibodies, anti-virals, and convalescent plasma.

Much data are still missing, and we are still only at the beginning (not the end) of this story. As Tom Petty said, “Waiting is the hardest part.”

We do know that Emergency Use Authorization (EUA) is only one step in getting the treatments that those with CLL / SLL badly need. Rapid distribution, broad and equitable access, and manageable out-of-pocket cost must happen for these monoclonal antibodies and antivirals to do any good.

With so many unknowns, I am reminded of a few of my longstanding pointers about dealing with CLL:

  1. Expect the unexpected
  2. Risk is impossible to eliminate
  3. You may need to make difficult decisions with imperfect knowledge and contradictory advice

We have all learned to live with cancer, and now we are learning to live with COVID-19. Living with uncertainty may seem to be the biggest challenge. But I say it’s always been uncertain. COVID-19 just pulled the covers off and exposed the bare reality that has always been there.

To quote Rabbi Nachman of Bratslav (1742-1810): “The whole world is a very narrow bridge, but the most important thing is to not be afraid.”

Take some deep breaths, make the best decisions that you can for yourself, be prepared to change them on a dime, and don’t forget to smile, laugh, and enjoy every day and every moment as much as possible.


I don’t plan to travel with the rise of Omicron and so many unknowns and shortages.

The next few months will be trying, but, and this is a big but, as long as COVID doesn’t pull another radical makeover on us, things should look better for the immunocompromised as early as this spring.

With so many therapies authorized and the commitment to improve access, and the ironic possibility that Omicron could “immunize” all the unvaccinated, the world could become a safer place for us sooner than we imagine.

That said, if you want to look foolish, make a prediction about COVID. I have no doubt this pandemic will pass. But I have no idea when or how.

May this season of miracles bring some miracles to our weary and wounded whole narrow world.

Stay strong. We are all in this together.

Brian Koffman, MDCM (retired), MS Ed (he, him, his)
Co-Founder, Executive VP, and Chief Medical Officer (and a person with CLL / SLL)
CLL Society, Inc.

CLL Society - COVID-19

When appropriate, the CLL Society will be posting updates and background information on the present Coronavirus pandemic focusing on reliable primary sources of information and avoiding most of the news that is not directly from reliable medical experts or government and world health agencies.