The publication examines the relationship between the use of ibrutinib and acalabrutinib with the incidence of second primary cancers.
There are data on risk factors for second primary cancers as well as cumulative incidence rates of second cancers.
In CLL patients treated with ibrutinib or acalabrutinib, an overall incidence of SPM x times the expected incidence in the general population was observed.
The post will attract others, not just those in treatment now.
To clarify, the study authors concluded that neither ibrutinib nor acalabrutinib altered the incidence of secondary primary malignancies in CLL patients. The authors were anticipating a lower incidence of SPMs with these targeted therapies, but found the incidence unchanged.
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Yalokin
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Thank you CycleWonder you've made me feel better. You see im guilty of being curious andwant to know everything . Neil tells me over and over again to stop reading and I don't listen.
Most of these types of studies are looking backwards so just by that, you know that the data does not apply to you.
You, if you ever start treatment, will be taking medications not available 10 years ago. So while their analysis is interesting, it may not even be relevant for you.
CycleWonder, my doctor gave me the options for cll treatment available and it wasn't many, ibrutinib, aclarabrutinib, venetoclax , and the combinations with these drugs. Aren't some of these 10 years old? That was 3 years ago.
FDA approvals for CLL treatment for venetoclax and acalabrutinib were May and November 2019 respectively. Ibrutinib was FDA approved for CLL in February 2014, but only for second line treatment, i.e. for previously treated patients. Combination treatment trials really only got started not long after venetoclax was found to be such an incredibly quickly working drug against CLL, giving unprecedentedly high uMRD rates in monotherapy trials. That would have been around 2018/early 2019.
You'll have some earlier clinical trial patients e.g. going back 10 years now for ibrutinib. However to do this kind of study, you need very large group of patients that meet the study criteria, who have lived long enough for secondary cancers to become apparent.
From the study, with the underlining my emphasis;
"Treatment was with ibrutinib in 545 patients (79%) and acalabrutinib in 146 patients (21%). 136 patients (20%) were treatment naïve prior to ibrutinib or acalabrutinib treatment."
Please keep this in perspective!
Out of 691 patients, there were only 24 patients who died with a secondary primary malignancy. Per the study report, "Among deaths due to SPM, four deaths were in patients with SPM diagnosed prior to start of BTKi with subsequent progression while receiving BTKi and 20 deaths were in patients with SPM diagnosed after starting BTKi treatment. The most common SPM diagnoses leading to death were lung cancer in five patients, tMDS/tAML in five patients, and Merkel cell carcinoma in three patients (Suppl Table 2). "
As the study mentioned earlier, therapy associated myelodysplastic syndrome (tMDS) and acute myeloid leukemia (tAML) are due to a previous CLL therapy, that is, FCR.
So out of the 691 patients in the trial, just 15 patients who had been on a BTKi treatment died from a SPM which was presumably not caused by a previous CLL treatment, after starting the BTKi.
Neil thanks for always explaining things to me thoroughly. I truly appreciate your time to this community and of course all administrators, volunteers and everyone else.
Definitely not! The authors were expecting to see those treated with a BTKi to have a lower risk of other cancers, but so far they haven't been able to detect any difference. It will be interesting to see whether the results change as more patient data is accumulated. See healthunlocked.com/cllsuppo... and my reply above healthunlocked.com/cllsuppo...
It's definitely a wake up call for smokers though!
"The most commonly observed invasive SPM in our cohort of patients was lung cancer, with 14 cases including 12 cases of Non-Small Cell Lung cancer (NSCLC), one case of small cell lung cancer...
Two of 12 patients diagnosed with NSCLC were never smokers."
"Four of five patients with bladder cancer had a prior smoking history."
Excellent perspective… also the risks of progression by not taking BTKs are much worse. Obviously there are risks with any medication, in my humble opinion the risks of not taking medication when the time comes outweigh the risks of taking them. Today we are lucky to have all these new generations of drugs and interventions that were not available just 10 years ago. It’s all depends how we look at the glass, half full or half empty…
I understand anxiety and depression have lived it. I don’t know if you readbut I found out I had cancer 3 months ago and it is my husband with CLL with u-mrd now. I know your diagnosis frightens you but remember in most cases it is years and years before treatment is needed and even people now who do need treatment have so many options. Most cancers are more aggressive and require much more aggressive treatment many of which like chemotherapy and radiation and surgery while there is much progress in CLL treatment chemo is hardly used if at all. Surgery would be exceedingly rare while immunotherapy and btk inhibitors have been so successful. There are tools to address treatment side effects. Lucky for me my cancer was likely cured by surgery but I know the risk of it returning is high. If it does my options are limited to harsh chemotherapy and radiation. So please try to live your life now while you are still so young and treatment free. When I had my clinical depression I was only 38. I thought that was so old. Now I only wish I had known then what I do now at 72 and would have savored every day!
I began treatment with Ibrutinib in 2014. Despite what this article says, I don't regret having been placed on Ibrutinib. 2014 wbc 300,000. Current wbc 12,000. I don't have any regrets.
I still don’t need treatment, but when the time comes, I would not hesitate to take a newer generation of BTK inhibitors… These numbers are not of concern to me, just by having CLL the chance of having other issues increases considerably, so this is par for the game…
Thank you. The summary is the most important part for me. The reasons for developing cancer are so many that nobody would be able to disentangle all of them in each specific case. These statistics are interesting for insurance companies. But quite irrelevant for a specific person and his prospects. Too many moving parts.
My son, a bioinformatician, often reminds me of the problem (made worse by the media) of describing risk as ‘times’. This large study in nature, for example, helped put this in perspective for me:
“attributing 38.85 excess cancers per 10,000 PYs”, where PY is person year. This means in their worst case analysis, which included many folks doing radiation and very old treatments, that one’s average chance of getting a secondary cancer would be about .4% per year higher per year than the normal person. Or put another way, 4/1000. And this ignores how far cancer treatments have come.
The lesson for me is to get screened regularly, and keep doing the healthy things to bend the numbers my way 😀. My opinion is that the diligence of the folks on this forum may actually lead to better outcomes than the average person!
Bobby, I second your point. It takes a little more oncological vigilance on our part. The rest is pretty much out of our control, except for a decent diet, exercise, etc.
We must be informed anyway. Otherwise, we are doing ourselves a disservice. There is such an expression in Bulgarian. I don't know how to translate it meaningfully. The meaning is that our ignorance and lack of information can come out "through our noses".
People should know that, in principle, any cancer increases the probability of a second, third and so on. I'm not talking about CLL here at all. Because genetic disorders (such as TP53) are characteristic not only of CLL, but of a number of other oncologies. However, this is NOT mandatory!
And it is in small percentages!
I understand that there are people who get stressed by the data for any oncology. Probably even most get stressed.
The more uninformed people are, the more stressed they become.
I do not recommend them to read such posts, so that it does not affect them badly.
I don't see anyone here posting any secret data that is not available on the net.
And something important: people, there are much more serious diagnoses than ours! Never forget this!!!
On this occasion, I will allow myself to tell a true case from about 20 years ago, with which to demonstrate how everything is relative.
I had two friends (one is still alive). I share the incident. One of them had a man's handbag stolen with 1000 dollars in it. He was a little distracted in general. And he called the other on the phone and called him "Ice" (his name is Hristo ), today they stole 1000 dollars from me (wow). And on the same day, Hristo's car was broken into and integrated circuits and so on for about 5000 dollars were stolen from his trunk. And Hristo is answering him on the phone, but - I had goods stolen from me for 5000 dollars don't complain"(At that time my salary was about 330 dollars).
And the other friend then told us, "and when I heard that you had 5 times more money stolen from you in goods, I felt a light, light feeling, and the woman and I immediately took out 1 bottle of whiskey and drank it (and his wife was Polish and not it took a special occasion to raise the bottle).
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