Interestingly no real difference between watch and wait and treated patients and a BTK inhibitor did not appear to confer a survival advantage
Key Points
*Both watch and wait and treated CLL patients when admitted for COVID-19 have high mortality rates
*Receiving a BTKi for CLL at COVID-19 diagnosis severe enough to require hospitalization did not influence case fatality rate in this study
Given advanced age, comorbidities, and immune dysfunction, CLL patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease-19 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL patients through this evolving pandemic.
CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n=198) were included. Hospital admission occurred in 90%. Median age at COVID-19 diagnosis was 70.5 years. Median CIRS score was 8 (range 4-32). Thirty-nine percent were treatment-naïve ("watch and wait") while 61% had received ≥1 CLL-directed therapy (median 2, range 1-8).
Ninety patients (45%) were receiving active CLL therapy at COVID-19 diagnosis, most commonly BTK inhibitors (BTKi; n=68/90, 76%). At a median follow-up of 16 days, the overall case fatality rate (CFR) was 33%, though 25% remain admitted. "Watch and wait" and treated cohorts had similar rates of admission (89% vs. 90%), ICU admission (35% vs. 36%), intubation (33% vs. 25%), and mortality (37% vs. 32%). CLL-directed treatment with BTKi at COVID-19 diagnosis did not impact survival (CFR 34% vs. 35%), though BTKi was held during COVID-19 course for most patients. Patients who continued to receive a BTKI (n=14) appeared to less frequently require supplemental oxygen (86%) and mechanical ventilation (21%). The subset of BTKi treated patients who continued therapy had a case fatality rate of 21%
These data suggest that the subgroup of CLL patients admitted with COVID-19, regardless of disease phase or treatment status, are at high risk of death. Future epidemiologic studies are needed to assess SARS-CoV-2 infection risk, these data should be validated independently, and randomized studies of BTKi in COVID-19 are needed to provide definitive evidence of benefit.
Jackie
PS. Photo is of two of our litter of puppies. All gone to new homes now, I loved them all ❤️
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This was very interesting, Jackie. Also a little scary, which makes all of us more careful...even more so! Have been out a few times fo doctor appts. However 4 months at home. My husband is essential worker, 84, but extremely healthy. I am almost 82 with comorbidities, so think I will have hubby take our puppies in for vet shots. Thank you for all you do.
Thanks for the info. My vet says the will come to door for each puppy and return them to car. Did not say how to pay or talk, but sounds good to me! Sitting in car will be hot tho. Will have to keep it running with AC. Very hot in Texas!
I noticed Furman on there too Len and this study doesn't seem too consistent with what we were discussing.
Its still confusing. It is not all that surprising to me with a median age of 70 that cll patients who are hospitalized with covid have a one third mortality rate. I am sure that is higher than the general population of hospitalized 70 yr old plus covid patients, but I assume that rate is high too.
The most concerning stat to me, if I read it right, is that cll patients with covid have a 90% hospitalization rate. Thats truly scary if true and seems very inconsistent with what you thought Furman's thoughts were on cll and covid.
I guess the numbers could be skewered if cll patients with milder covid cases were not reporting them to their cll doctors.
Even so, these numbers sure look bad for us. I guess one way to look at it is two thirds survived, but merely surviving covid doesnt mean one is not left with lung damage and other problems.
I sure hope I am not fully understanding this, its not good.
When it says 'symptomatic' the report does not define the term. So, if you look at the broad spectrum of symptoms, 90% seems awfully high and I'm struggling with the idea that 90% of CLL patients who had any symptoms would be hospitalised.
I agree cajunjeff that it seems at odds with what Dr Furman seemed to be saying and also with what Dr Allan told my husband to convince him to come to NYC for a trial blood draw. Kind of makes me angry because we did end up going yesterday. We took lots of precautions and only did the blood draw and did not wait around for the doctor visit before we beat it out of town, but still the COVID risk was much more than not going. Dr Allan basically told him he would be fine if he contracted COVID because he is fit and not obese. At least we now have this report to support our argument the next time an important test comes up in the trial that just can't be done remotely. It doesn't seem right though that we would have to make this argument to one of the authors of the paper!
Two bundles of joy in those beautiful dogs. Sorry you couldn't keep.
Thank you for this article. It confirms my feeling of needing to be as compliant to the safe routine as is possible. I certainly hope all will stay safe.
Hi. Let us know how the train journey goes, please. It’s the only way we will ( eventually!) be able to go to see our sons and grandchildren 🙁and when we looked on line it doesn’t look as though much is being done to distance people, other than rely on people being sensible... and we all know how that goes! 🥴
Of course, Fran, but I don’t suppose it will be for quite a while yet. And I was just telling a friend about it (who lives over 40 miles away), and she offered to come and get me and take me there. So generous - I was surprised and grateful.
I know it is scary out there. As I have said before, we have cancer of the immune system and will have to do necessary things to protect ourselves long after CV-19 has died down. fifty percent of CLL patients expired from pneumonia before CV-19 ever showed up. You will be able to take your train ride as before, with same precautions you used to take. Blessings.
"CLL-directed treatment with BTKi at COVID-19 diagnosis did not impact survival (CFR 34% vs. 35%), though BTKi was held during COVID-19 course for most patients."
"With the caveat that most patients on BTKi at time of symptomatic COVID-19 diagnosis had their BTKi held (79%), receiving a BTKi at the time of COVID-19 diagnosis did not appear to impact survival (case fatality rate 30% for all patients receiving BTKi alone in or combination, 33% for patients receiving BTKi monotherapy vs. 35% for patients not on BTKi). BTKi treated patients diagnosed with symptomatic COVID-19 who stayed on therapy (n=14) appeared to less frequently require supplemental oxygen (86%) and mechanical ventilation (21%). The subset of BTKi treated patients who continued therapy had a case fatality rate of 21%."
Thanks for picking up the fact that 79% of patients on Ibrutinib had it withheld after getting Covid. I've not read and in past did not seem able to get into the papers on ASH site. But honestly, given results from other trials, this one does not impress me too much from what I can see here.
Thanks, I was trying to do this on my phone and didn't see the full PDF. I've included the link to that now and also amended the original post to reflect the stats for those that continued their BTKi. Presumably, it's hard to administer the BTKi to those on ventilators
On other trials patients are able to take their Acalabrutinib capsules. Some were breaking the capsules into liquid that fully dissolved the powder. AstraZeneca may tell you what method they've been using.
It still isn’t always a death sentence. Think of it more like Russian roulette. It’s a game you don’t want to play. But if you find yourself in the middle of it then at least you know you have a higher chance of surviving than not. Jeff is right by definition these studies over estimate the risk because they are case report studies and so can’t catch mild cases. I wish they’d say that in the papers. But for sure we are wise to take radical steps to not catch this thing.
I agree it's still NOT a death sentence. It's funny how the mind looks for any positive to latch onto and I had convinced myself it was ok through some of the other things I had read. Although this article set me back a bit (denial is not just a river in Egypt😉), it is good to know and I appreciate Jm954 for posting it. It's an important reminder that we can't take any of this lightly. I still plan to live my life though, as carefully as I can but still with a bit of gusto because as one smart CLL'er said, tomorrow is promised to no one! Blessings to us all!
I do not want to downplay at all how serious covid can be for us with cll. This study is a sobering reminder of that. But I do think the study overstates the current risk. Here is what the study said:
CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n=198) were included. Hospital admission occurred in 90%. Median age at COVID-19 diagnosis was 70.5 years. Median CIRS score was 8 (range 4-32).
So it seems the way they gathered the cll group is to survey cll doctors and identify "symptomatic" patients who reported testing positive for covid. This could exclude a good number of cll patients who never reported covid symptoms to their doctors and cll patients who had asymptomatic cll. How many people might that be? Its almost impossible to guess, but it is likely the more serious covid cases were most likely to be reported.
The group they ended up with had a median age of 70, which made is a high risk group purely as a function of age. The median cumulative illness rating for this group (8) was high as well, meaning most had other comorbidities besides cll. And its a very small sample size.
Presumably this survey includes many early cases, when mortality rates were higher across the board. They are getting better with treating covid. The survey appeared inconclusive to me on whether ibrutinib helps since most were taken off ibrutinib.
Its intuitive to me that having cll puts me at greater risk of being hospitalized and greater risk of dying if i get covid. My best guess is this study overstates that risk in that it probably excludes most all asymptomatic cll patients and many with mild symptoms.
But even if its off by half and that my risk of hospitalization is 45%, not 90, and my risk of death is 15%, not 33, its still too much risk for me to do anything other than take full precautions.
Agree with your points... including that tracking only symptomatic COVID19 patients would seem to ignore a whole segment of the CLL-Covid-having population. So the goal for CLLers would be to remain symptom free.
To your point about early cases: I notice is the data was collected from Feb to April 30 when presumably the learning curve for dealing with the virus in general was still pretty sharp. I hope that data on that same sort of cohort would be a bit better from June or July to Sept for example... but that might be wishful thinking on my part.
The article also notes that the patients who stayed on the BTKi therapy at Covid19 diagnosis had lower incidence of oxygen support and fatalities (but it was only 14 patients). That would seem to match with other information we've seen, if I recall.
At the end the article does comment on all of these limitations.
Cumulative Illness Rating Scale-Geriatric (CIRS-G) Quantifies burden of disease in elderly patients (comorbidity scale). Elderly patients (often defined as age >65 years). May be more accurate than the Charlson Comorbidity Index in geriatric patients (Borson 2011).
Had a look at the CIRCS and did mine - not happy! Quickly accumulated 7 points - 4 for CLL, 2 for HT (thanks Ibruitnib) and 1 for not having 2020 vision.
Just when I was beginning to think it may be safe to emerge from the house 👹
It’s beginning to feel increasingly depressing and today we have been told here in the U.K. not to expect this to go away anytime soon despite Boris hoping for a happier Christmas with no Covid pressies!
This is much needed data confirming the worries we all have. The fact that The Who is who on the CLL world is on this gives this a lot of credibility.
The number of infected patients needing hospitalization is extremely high but the data collection might be skewed since very likely only symptomatic patients were tested which would miss asymptomatic patients in this cohort.
What concerns me is the high mortality rate and the fact that still 25 were still hospitalized at the cot off at 16 days. What happened to those patients ?
On the positive side we learned much more about this virus and we have better treatment options while not curative they are definitely supportive and might in combination reduce mortality. Among them remdesivir, dexamethason and convalescent plasma. So I believe we have a fighting chance if we (hopefully never) catch this virus.
I agree, this data was gathered early in the pandemic and things are more hopeful now for everyone in terms of treatment. We still need to be careful and assess risks when we go out though, at least I do!
When I go to the PDF of the actual article - I see a lot of information that really doesn't sit well with me.
I won't go over the article in detail, but I first wondered as to how precisely the authors chose the CLL patients to be included in the study. Are they representative of the whole CLL population - or are they picked as patients of all the CLL experts who authored the article? If so, that could be a problem. CLL specialists will have a more active set of CLL patients.
Also, I really would love to see an age breakdown. A median age of COVID patient at over 70 says to me there could be a lot of older patients. Of course older patients would have a higher mortality rate. That's been documented quite frequently.
Whether the numbers are accurate regarding a RANDOM CLL patient population or not, they do tell me that we should be worried about COVID. How worried - I am not clear.
I will say that this data is totally inconsistent with what my CLL Dr. (Dr. Steven Coutre) said to me in an appointment we had in June - regarding CLL and COVID. Totally inconsistent. I'm not sure what to make of that.
Better safe than sorry - but I really wish I knew the absolute risks.
the following percentage of COVID-19 deaths out of all deaths in the USA per age group is thus:
Age group % Deaths from all causes
Under 1 year 0.12%
1-4 years 0.56%
5-14 years 0.64%
15-24 years 1.14%
25-34 years 2.93%
35-44 years 5.30%
45-54 years 7.83%
55-64 years 8.21%
65-74 years 9.26%
75-84 years 9.51%
85 years+ 9.40%
All Ages 8.75%
Deaths due to pneumonia are very close to deaths due to COVID-19 for those older than their mid 20's. There were 121,374 deaths noted as due to COVID-19 and 131,332 due to pneumonia. More young people died from pneumonia than COVID-19. There's also a category for deaths from both COVID-19 and pneumonia, (52,431). People were 10 times (45 to 54) to 30 times (85+) more likely to die from COVID-19 than the flu.
The male fatality rate for COVID-19 is slightly higher than the female fatality rate for higher age group brackets, for an overall rate of 9.01% vs 8.46% or a 6.5% difference.
Thanks. The odd thing is that many states differ in mortality rates overall. The CDC likely has that somewhere, but to compare would be nearly impossible. I gather it has to do with testing standards and the fact that certain areas have larger amounts of susceptible populations.
I do hope that monoclonal antibody therapies start coming into being soon. Those will help a great number of people - people with CLL also.
It’s strange in that I have never seen anything like the data you have posted (all ages in one place) until you have posted it here. If the average person here saw this data - especially the younger ones - they may not trivialize COVID nearly as much as they do. In the US, our biggest problem is ourselves.
The dataset goes down to state level, but inconsistent standards don't help, plus now we are in a transition where the data is now being sent to the HHS.
The numbers don't seem to make sense. If, in the US, we have had about 4,000,000 cases (test confirmed) and 140,000 deaths - then how does the CDC come up with an 8.75% overall mortality rate?
I wish I could find a more positive report but all I can do is post what I find and help to make people aware. There is a lot of granular detail missing from this report but I posted it because of the reputation of the authors. I hope Dr Coutre's experience reflects current outcomes as we've learnt a lot since this data was gathered early in the pandemic.
Yes, he did not express any out of the ordinary concern. Dr Coutre is not the type to “soften the blow” at all as well. He says what he thinks - good and bad.
Looking at this only a very small advantage is gained by recieving a BTK inhibitor , but the death rates 33% percent is similar to rates seen in patients without blood cancer l make this assumption on the mediam age in the study which was 70 plus be interesting to see what fatality rates are in a lower age group .
In my case studies I found that spending time with Labrador puppies decreases the probability of contracting Covid 19. It is determined that this phenomenon is influenced through spending more time with puppies and less with less humans possibly having been exposed the virus.
I can confirm your findings of an inverse relationship between possible virus exposure and time spent playing with puppies. The cohort is only of 1, however, I think the data is completely reliable.
Hmm, I have CLL, near remission with the help of ibrutinib and scheduled for a minor surgery tomorrow for correction of a "trigger thumb." I'm told an operating room is the cleanest place you could be and I don't plan to be in a waiting room for long, wearing mask of course. I'm 79, and healthy except for that pesky CLL, which thankfully has never been complicated for me. My oncologist/hemotologist did not recommend against the procedure. He said to stop ibrutinib for 5 days pre and post. Do you think I've made the right decision to go on with the surgery?
OK .... I can find a number of things that really are strange about this paper - and believe me, I am not trying to put my head in the sand. I just want to make sure how real this data is.
I see more than 60 authors and 198 patients. Given that, it may have been very difficult to find "peers" to review this article without rocking the medical political boat!
Nevertheless (the question that really defines how legitimate this data is), where did these 198 patients come from? Were these absolutely random CLL patients? Were these CLL patients commonly seen by the "authors" ? The CLL data of these patients is so precise, that it seems as if they were regularly seen by the CLL experts. 45% of them were in active treatment - again suggesting they were active patients of a CLL specialist. This could sharply skew the data toward CLL patients that needed and had regular CLL specialist care.
Yes, many countries have centralized medical records - but many do not - definitely the US is one of them.
How many people here would have CLL Drs that even knew you had contracted COVID? You would go to local ERs - not likely to call your specialist and have him/her fill out a questionnaire concerning your CLL status. At the time of the data collected in the study (March-May), COVID was overwhelming ER facilities.
Bottom line is that the article makes very little sense as to where they got a hold of 198 CLL patients. Where they got the patients could skew the data in either direction by quite a bit.
The 60 authors tells me that these Drs contributed case reports and then there was some statistical analysis undertaken to write the paper . A similar information gathering exercise about COVID and CLL is being undertaken in the UK at the current time by the UK CLL Forum.
We can discuss where the patients came from but it looks as though they were patients seen by CLL specialists from around the world, primarily USA, a few UK.
I know the data isn't what we want to hear but I'm sure it's been faithfully reported by these Drs who have their reputations at stake. I'm equally sure that for every one of these reported patients there may have been many more who did not need hospitalisation and didn't necessarily come to their attention.
Agreed. At this chaotic stage of the pandemic, I don't think it's possible to analyze data of a low incidence cohort (such as CLL patients) without seeing the "high profile" patients first.
What I get from this article is to definitely stay away from COVID (if possible). I still don't walk away with any numbers of what will happen if I do.
I really appreciate that you bring this data to our attention. Qualitatively - it makes it's point. That's all that matters. Thanks.
I wonder how many of our community like me have read and reread through this post and replies and ended up with a brain trying to escape out of their ears. Information and confusion overload, though I appreciate that many are ultra interested and want every tiny detail examined and understood. Especially those who still have to be out in the world working, I certainly get that.
For me it is simple really, I am immune compromised and no one telling me I can do this or go there in August will change my life until there is a vaccine that works for us all.
I shop early at 7 am on Monday morning as it is quiet, with mask in place and hand gel for when I return to the car. I pop into the garage shop on Saturday morning at 7 am similarly clad to pick up any items I have forgotten. The rest of the time I walk where it is quiet and exercise using a wii.
Exception made after 18 weeks to have my daughter visit. Can I be sure I will not get covid19, of course not, but I will know for the sake of my family I did all I could to stay safe.
Frightening to say the least. I'm W and W, and have to work full time. Just returned from a driving vacation, and tried to be as cautious as possible...masks, etc. Only carry out or cooking in. Maybe I need to walk around in a space suit with a gas mask.
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Cardiotoxicity in patients treated with acalabrutinib
