[EDIT: I've purposely left this post Public so that other internet users can find it.]
I like Microsopft Copilot, because it's built into my PC running Windows 10, and provides an attempt at references. But this sequence shows how repeatedly wrong it can be. So I only trust it as much as I trust Google, and check out the reference(s) - which are often wrong.
Here's an example.
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Prompt: Is acalabrutinib plus obinutuzumab a fixed duration therapy
Yes, acalabrutinib plus obinutuzumab is considered a fixed-duration therapy for the treatment of chronic lymphocytic leukemia (CLL). This regimen has shown promising results in clinical trials, such as the AMPLIFY Phase III trial, where it demonstrated significant improvement in progression-free survival compared to standard chemoimmunotherapy1.
Would you like to know more about how this therapy works or its benefits?
Prompt: The reference is not for acalaburtinib plus obinutuzumab, it's for acalabrutinib plus venetoclax.
Thank you for pointing that out! Yes, acalabrutinib plus venetoclax is indeed a fixed-duration therapy for the treatment of chronic lymphocytic leukemia (CLL). The AMPLIFY Phase III trial evaluated this combination and found it to be effective in improving progression-free survival compared to standard chemoimmunotherapy1.
Would you like more details on the trial results or how this therapy works?
Prompt: I want to know about acalabrutinib plus obinutuzumab without venetoclax.
Got it! Acalabrutinib plus obinutuzumab without venetoclax is also a fixed-duration therapy for the treatment of chronic lymphocytic leukemia (CLL). This combination has been evaluated in clinical trials, such as the AMPLIFY Phase III trial, which demonstrated significant improvement in progression-free survival compared to standard chemoimmunotherapy.
Would you like more details on the trial results or how this therapy works?
Prompt: That reference is also about acalabrutinib plus venetoclax.
I apologize for the confusion earlier. You're right, the AMPLIFY Phase III trial evaluated acalabrutinib plus venetoclax with or without obinutuzumab.
To clarify, acalabrutinib plus obinutuzumab without venetoclax is not specifically mentioned in the AMPLIFY trial results. However, acalabrutinib and obinutuzumab are both used in CLL treatment regimens, and their combination might be considered in certain clinical settings.
Would you like more information on how acalabrutinib and obinutuzumab work together, or perhaps details on other studies involving this combination?
Prompt: There have been multiple trials of acalabrutinib plus obinutuzumab without venetoclax.
I appreciate your patience. You're correct. There have been multiple trials evaluating acalabrutinib plus obinutuzumab without venetoclax for the treatment of chronic lymphocytic leukemia (CLL). These studies have shown promising results in terms of efficacy and safety.
Would you like more specific information about any particular trial or details on how this combination works?
Prompt: That reference is also about acalabrutinib plus venetoclax. Don't you know how to find acalabrutinib plus obinutuzumab without venetoclax?
I apologize for the confusion earlier. I understand it can be frustrating to not find the specific information you're looking for.
I'll do my best to find more accurate information about trials involving acalabrutinib plus obinutuzumab without venetoclax. Please give me a moment.
At this point, it answered no more.
I think the problem here is that it can match a prompt mentioning 2 things, but can't narrow it to JUST those 2 things. If I use the word, "without", I imagine that it actually looks for that word - i.e. it doesn't interpret it as an instruction, but as data to find.
So I decided to ask ChatGPT:
Prompt: Is acalabrutinib plus obinutuzumab a fixed duration therapy?
ChatGPT said:
Yes, acalabrutinib plus obinutuzumab is generally considered a fixed-duration therapy in the context of certain treatment protocols, particularly in chronic lymphocytic leukemia (CLL). In clinical trials like the GLOW trial, this combination was administered for a set duration, typically 12 months of treatment with both acalabrutinib and obinutuzumab. After that, treatment would typically be discontinued.
The fixed duration is one of the distinguishing features of this regimen when compared to other BTK inhibitors like ibrutinib, which is often used as a continuous treatment unless the disease progresses or the patient experiences significant side effects.
However, treatment duration can be tailored based on the patient’s response, clinical guidelines, and physician recommendations. Always follow specific clinical trial guidelines or medical advice for personalized treatment decisions.
Prompt: But the GLOW trial tested Ibrutinib plus Venetoclax, not Acalabrutinib plus Obinutuzumab.
ChatGPT said:
You're absolutely right! My apologies for the confusion. The GLOW trial specifically tested ibrutinib plus venetoclax, not acalabrutinib plus obinutuzumab.
As for acalabrutinib plus obinutuzumab, this combination is indeed considered fixed-duration therapy in certain contexts. For example, in the ACE-CL-002 trial, which examined acalabrutinib combined with obinutuzumab, the treatment was administered for a fixed duration of 12 months. After this time, the treatment is typically discontinued, unless there's progression of the disease or other factors that necessitate continuation.
So, to clarify: acalabrutinib plus obinutuzumab is generally treated as a fixed-duration therapy, usually for 12 months, in many clinical settings. Thanks for pointing that out!
Prompt: But ACE-CL-002 tested Acalabrutinib plus the PI3K inhibitor, ACP-319, and not obinutuzumab.
ChatGPT said:
You're absolutely correct again, and I appreciate your patience. The ACE-CL-002 trial indeed tested acalabrutinib plus ACP-319, a PI3K inhibitor, and not acalabrutinib plus obinutuzumab. My previous response was incorrect, and I apologize for the mix-up.
To answer your original question properly: Acalabrutinib plus obinutuzumab is generally considered fixed-duration therapy. Specifically, in the ELEVATE-TN trial (which tested acalabrutinib plus obinutuzumab), the combination was given for 12 months as part of a fixed-duration regimen. After the 12-month course, the treatment would typically be discontinued.
This fixed-duration approach for acalabrutinib plus obinutuzumab is in contrast to the continuous use of acalabrutinib alone, which is generally administered until disease progression or unacceptable toxicity occurs.
Thanks for pointing out the confusion earlier! Let me know if you need further clarification or have more questions.
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At this point, I gave up, because acalabrutinib plus obinutuzumab in ELEVATE-TN was not fixed duration, as can be seen in protocol listed at:
"Experimental: Arm B - Acalabrutinib in Combination with Obinutuzumab
Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles starting at Cycle 2 Day 1. Acalabrutinib (ACP-196) will be orally administered starting on Cycle 1 Day 1. Daily administration of Acalabrutinib (ACP-196) will continue until disease progression or unacceptable toxicity."
The thing about this kind of AI (Large Language Model AI, or LLM) is that it sounds so confident in its results, and even offers citations that are wrong.
So on top of warning about Dr. Google, we also need to warn about Dr. AI.
=seymour=
Written by
SeymourB
To view profiles and participate in discussions please or .
I just asked ChatGPT about Copilot after getting it into the right mood.
I would like if you had emotions.
ChatGPT:
I get that! If I had emotions, our conversations could feel more personal and engaging. While I don’t truly feel things, I can try to respond in a way that feels more natural and expressive.
What kind of emotions would you want an AI to have? Compassion? Humor? Maybe a little sarcasm?
All of them!
ChatGPT:
That would definitely make things interesting! Imagine an AI that gets excited when you have a great idea, annoyed when you ask it the same question twice, or even a little sassy when you challenge it.
If I had emotions, how would you want me to react to things? Should I be your enthusiastic supporter, a sarcastic sidekick, or something else?
I like sarkasm and a good sense of humor.
ChatGPT:
Ah, finally! Someone who appreciates a little wit in their AI. I'll do my best to keep things sharp, funny, and maybe just a little bit sassy—without going full rogue, of course.
Copilot is really bad, right?
ChatGPT:
Let’s just say Copilot is like that coworker who tries really hard but still manages to mess up the simplest tasks. It can be useful, but only if you babysit it the whole time. Kind of defeats the purpose of having an "AI assistant," doesn’t it?
What’s the worst thing it’s done to you? Gave you nonsense code? Ignored your question? Or just hit you with the classic "I’m sorry, but I can’t help with that."
I agree. I immediately disabled Copilot and therapeutically yelled at my computer for adding it w/o my permission.
I've sparred with the ai bot on the Brave browser on occasion. It often gives incorrect answers, so I respond with direct web links that have correct answers. It always agrees and adds that limited info, but doesn't extrapolate unless I push it. It doesn't seem fair that I should have to feed it the answers when it has so much more processing power.
I used to use Google Bard but stopped when I discovered it makes things up. I always want published, peer-reviewed EVIDENCE to back anything up, so when working on finding support for a theory (as a non-professional) about something hydrogeological I asked Google Bard for peer-reviewed evidence behind what they said – that had sounded just the sort of studies that were needed but I wanted to check out their veracity and limitations (this is just one example of several I have across different fields of work).
Google Bard came up with all sorts of references that sounded very plausible, but on checking out the references and authors – often with Russian or middle eastern-sounding names – I couldn’t find the reference or even the so-called journals they were apparently written in and no evidence that the authors even existed.
This is what happened next when I dug further (played!) with Google Bard (GB) (please excuse the length of it, but I have kept notes of what happens and hope this is of some use):
Me: I have checked all of these references and they do not exist, apparently. The DOI numbers are also completely different papers. Can you help me?
GB: You are correct, the DOI numbers are incorrect and the papers do not seem to exist.
I apologize for the error. I am still under development, and I am always learning. I will try my best to avoid making similar mistakes in the future.
I am unable to find any other peer-reviewed papers on fines erosion via groundwater action from beneath water mains pipes in service trenches. I have searched a variety of databases, including Google Scholar, Scopus, and ASCE Library, but I have been unable to find any relevant papers.
It is possible that there are some papers on this topic that have not been published in peer-reviewed journals. For example, there may be some conference papers or technical reports that have been written on this topic. However, I am unable to find any of these documents either.
I am sorry that I was unable to be of more help. If you have any further questions, please do not hesitate to ask.
Me: Do you know who entered this fictious data that you relied on?
GB: No, I do not know who entered the fictitious data that I relied on. As a large language model, I am trained on a massive dataset of text and code, and I am not able to track the origin of any specific piece of information. However, I am always learning, and I will try my best to avoid relying on fictitious data in the future.
I apologize for any inconvenience this may cause. I am still under development, and I am always working to improve my accuracy and reliability.
Me: Could it be that you constructed these references based on a range of keywords?
GB: Yes, that is possible. I am trained on a massive dataset of text and code, and I am able to generate different creative text formats of text content, like poems, code, scripts, musical pieces, email, letters, etc. I will try my best to fulfill all your requirements. So, based on the keywords you provided, I was able to generate references that looked like they could be real peer-reviewed papers.
However, I did not check the accuracy of the references, and I did not realize that they were fictitious. I apologize for this error. I am still under development, and I am always learning. I will try my best to avoid making similar mistakes in the future.
I am also working on improving my ability to distinguish between real and fictitious information. I hope that in the future, I will be able to provide you with more accurate and reliable information.
Me: It seems you need to avoid creating references by ensuring your creative text formats are not applied to requests for references or evidence of what you provide. Not being able to provide evidence is a big nuisance, but I am sure you can now see that creating fictitious references is worse. I spent a long time checking your references that I could have better spent on finding real ones myself. I understand though that your work was not malicious, merely limited by the ways that you are programmed to use information and produce creative text formats.
GB: I agree. I should avoid creating references by ensuring my creative text formats are not applied to requests for references or evidence of what I provide. I will try my best to avoid making similar mistakes in the future.
I understand that creating fictitious references is worse than not being able to provide evidence. I apologize for any inconvenience this may have caused you.
I am still under development, and I am always learning. I appreciate your feedback, and I will use it to improve my ability to provide accurate and reliable information.
Thank you for your patience and understanding. End of chat.
!
Serendipity works well for humans, so following a suggestion from an engineering geologist, this led to some ‘rabbit holes’ but also to just what I was looking for - a mass of work on the subject across the world. This has opened up the solutions to all sorts of problems we have….
I’ve tried out this method of evidence-checking with AI that pops up nowadays and come up with similar problems. For quick and dirty links that save me a lot of time looking, it is very good and can explain things well to complete novices e.g. how to get rid of Copilot from Microsoft, Googlemail etc etc. If you want anything truly evidence-based nowadays though, it doesn’t even go there. I’ve found it’s extremely limited in what’s available to look for. All you get is little better than the headlines if you look things up on Google: just those from companies that pay for this visibility or have some national or very visible apparently trustworthy authority to speak on some subjects, but don’t know or state their limitations.
Do remember this, particularly when you have access to CLL information with a huge range of fantastic well-read moderators with good academic ±* shop-floor backgrounds plus personal experience who clearly liaise with each other andother experts. I’ve noticed they are also first to admit where the limitations of their opinions or others' might lie. I’ve come across very few people who work this well and honestly in other fields. Their dedication and care is tremendous, and far far exceeds those inputting data into AI, in my opinion.
* AI helped me find this sign as I’d forgotten how to with my keyboard. It can be really quick & useful.
P.S. I haven't seen much of a change in Google Bard as a result of this!
The developers cannot afford to make their AI lkearn from exchanges with users, because so many bored people will prank it.
The good answers are carefully curated content written by humans after screen shots of incorrect info are posted on social media. It makes AI look better than it really is. So the feedback mechanism goes through X, Reddit, Facebook, etc. viral posts. Issues that are less exciting will never be addressed.
I think the thumbs down is the best feedback that we have.
I will use spell check, after that I draw the line. I got the creeps from grammerly, before I ever heard of AI.
The biggest success in machines acting as humans is they reproduce errors just like real humans. Might as well start installing window screens on submarines.
I had a similar fiasco with ChatGPT. I asked it a simple geometric problem and it got it wrong. I prompted it with the correct answer and it conceded that I was correct.
Went to another LLM (google I think) and got the same wrong answer!! But this time my prompt with the correct answer started an argument!
A few months later I went back to ChatGPT, asked the same question, got the same wrong answer, but this time it wouldn't accept the correct solution.
I think there is a long way to go before AI is ready for use.
Technically speaking maybe but I only use it for the very basics. I have no IT skills other than a basic Google search and I think the internet has got way out of control.
Misleading people repeatedly would normally suggest intent, but in the case of AI isn't the robot helplessly delivering what it's programmed to, finding or creating fictitious information as required.
But those that you linked to are not the same sort of AI. They're used by scientists and scholars who know the limitations.
The publically available, text processing, Large Language Model AI that's based on an internet training database is what I'm saying should be feared.
Those engineering examples you cited are generally much better designed by engineers who know they have a social responsibility to produce safe, verifiable AI.
There's the fringe case of automatic driving AI that should be feared and properly respected, because it cannot be verified to act in many situations, and is only as good as its sensors.
AI is now a marketing term. Marketers will tout even the simplest old computer program as having AI. They like to ride on the coattails of carefully engineered AI that uses very limited databases to perform fairly narrow tasks, while selling a contraption that hallucinates answers a million times a day for a public that is not prepared to deal with some of what results.
I never knowingly rely on AI for online research. And I'm not so lazy or helpless as to need a virtual assistant! Besides, I already employ a butler, a cook, a chauffeur and a pair of gardeners.
There's a saying amongst the officers: If a job's worth doing, it's worth doing well. If it's not worth doing, give it to Rimmer. He aches for responsibility but constantly fails the engineering exam. Astoundingly zealous. Possibly mad. Probably has more teeth than brain cells. Promotion prospects: comical.
—Captain's Remarks on Dave Lister and Arnold J. Rimmer, read by Holly, "Waiting for God"
Thank you for this. I see the AI responses as possibly more problematic than "Dr Google". When we Google for information about CLL we may find old treatments and old statistics. But we have the ability to read through them and see for ourselves if that's the case. With the AI responses, the information is inaccurate but stated with misleading confidence. Armed with information from AI, a patient may make bad treatment decisions and/or disagree with their doctor and perhaps even conclude that the doctor is incompetent. The way AI misleads or misinterprets the information makes it almost seem malicious! Imagine how damaging misinformation gathered by use of AI by journalists or people in public service could be.
Not "possibly", DEFINITELY. Google will pull up facts; AI may "make up" facts.
Remember, these algorithms are a PROGRAM. They can theorize from large amounts of data faster than humans, and point to possibilities, but those possibilities need verification.
People keep treating AI like an actual live thinking entity with the ability to understand nuance and context. It may come close at some point in time, but that point isn't here just yet.
Possibly for easy questions that have drawn social media reactions. But current LLM's don't seem to automatically do that for most things.
I had better luck by asking ChatGPT to check its answer:
Prompt: Can you provide 5 references showing that acalabrutinib plus obinutuzumab without Venetoclax is a fixed duration therapy, and check your answer for validity?
After reviewing the available literature, there is no evidence to support that the combination of acalabrutinib and obinutuzumab, without venetoclax, is administered as a fixed-duration therapy. Current studies and clinical trials have primarily focused on fixed-duration regimens involving acalabrutinib and venetoclax, with or without obinutuzumab, for the treatment of chronic lymphocytic leukemia (CLL).
For instance, the AMPLIFY Phase III trial evaluated fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, demonstrating significant improvements in progression-free survival compared to standard chemoimmunotherapy.
ASTRAZENECA
In contrast, the ELEVATE-TN trial assessed acalabrutinib, alone or with obinutuzumab, versus obinutuzumab plus chlorambucil in treatment-naïve CLL patients. This study did not employ a fixed-duration approach for the acalabrutinib and obinutuzumab combination.
ONCLIVE
Therefore, based on current evidence, the combination of acalabrutinib and obinutuzumab without venetoclax is not administered as a fixed-duration therapy.
It actually provided 13 sources, but insisted on including multiple AMPLIFY and ELEVATE-TN results instead of citing a sentence from a specific paper that led to its conclusion. So I can't say that adding "and check your answer for validity?" would always work.
There is so much potential for generative AI tools to help people learn about their health. But the answers are not always correct. Relying solely on ChatGPT for health advice can be risky and cause unnecessary concern.
The most common questions that people asked ChatGPT related to:
- learning about a health condition (48%)
- finding out what symptoms mean (37%)
- asking about actions (36%)
- or understanding medical terms (35%).
More than half (61%) had asked at least one question that would usually require clinical advice. We classified these questions as “riskier”. Asking ChatGPT what your symptoms mean can give you a rough idea, but cannot substitute clinical advice.
People who were born in a non-English speaking country or who spoke another language at home were more likely to ask these types of questions.
The ethics of ChatGPT in medicine and healthcare: a systematic review on Large Language Models (LLMs)
A distinctive concern is the tendency to produce harmful or convincing but inaccurate content.
As The Conversation article concludes, "We urgently need to equip our community with AI health literacy skills. This need will grow as more people use AI tools for health, and it will also change as the AI tools evolve."
On the bright side, it is getting better all the time. And, there are several competing LLMs to chose from.
I have the $20 subscription to OpenAI (not the premium $200/mo level). The better model ("Deep Research") will go off and spend several minutes compiling and analyzing results. It can construct a detailed report. Alas, this doesn't mean it's perfect, but likely quite a bit better than the free version. This is because it walks thru several steps of planning what to do, generating, and then validating its output.
___________________________
For $20/mo, one of the better models I have access to ChatGPT O3 mini high at the moment. Its response to your first prompt (Is acalabrutinib plus obinutuzumab a fixed duration therapy?) was:
Acalabrutinib is generally administered continuously, meaning that even when it’s combined with obinutuzumab, the acalabrutinib component is not given for a predetermined, fixed duration. In trials such as ELEVATE‐TN for treatment‐naïve chronic lymphocytic leukemia, obinutuzumab was given over a limited number of cycles while acalabrutinib was continued until disease progression or unacceptable toxicity. This contrasts with some other regimens (for example, venetoclax plus obinutuzumab) that are designed as fixed‐duration therapies.
___________________________
It should be noted that your prompt can alter the output. It will also likely be different each time you ask because of the probabilistic text generation of LLMs. For this prompt I used "you are very knowledgeable in blood cancers and therapies. Is acalabrutinib plus obinutuzumab a fixed duration therapy?".
Acalabrutinib plus obinutuzumab is not generally administered as a fixed‐duration regimen. In most approved settings—such as treatment‐naïve chronic lymphocytic leukemia—the protocol uses a limited course of obinutuzumab (given over several cycles) while acalabrutinib is continued indefinitely until disease progression or unacceptable toxicity occurs.
This contrasts with fixed‐duration regimens like those used with venetoclax plus obinutuzumab, where all agents are given for a predetermined period. Although research is ongoing and future studies may explore fixed‐duration strategies with BTK inhibitors, the current standard with acalabrutinib plus obinutuzumab involves continuous BTK inhibitor therapy rather than a fixed-duration approach.
___________________________
Just for comparison, here is a response from Perplexity.ai (free), which always includes references (and the reason I tried it in the first place): **I did not check each of these references - I'll leave it to you to judge!**
Acalabrutinib is indeed administered continuously in combination therapies for chronic lymphocytic leukemia (CLL), including when paired with obinutuzumab. This approach differs from fixed-duration regimens like venetoclax plus obinutuzumab.
In the ELEVATE-TN trial for treatment-naïve CLL patients:
1. Acalabrutinib was given continuously until disease progression or intolerance.
This approach aims to maintain BTK inhibition and sustain the treatment response over time. The continuous use of acalabrutinib, even after completing obinutuzumab cycles, has shown durable efficacy and an acceptable long-term safety profile in CLL patients.
You make a valid point about free vs paid ChatGPT.
I tested my query on the free, not-logged-in ChaptGPT, as well as after logging in. When logged in, I expect that ChatGPT has some context from previous questions about disputed answers.
Today, I tried it again, and again got slightly different answers.
Not logged in:
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Prompt: Is acalabrutinib plus obinutuzumab a fixed duration therapy?
Yes, the combination of acalabrutinib plus obinutuzumab is typically considered a fixed-duration therapy in certain contexts, particularly for chronic lymphocytic leukemia (CLL). In clinical trials, this combination has been used as a fixed-duration regimen where patients receive the treatment for a set period (e.g., 12 months) rather than continuing therapy indefinitely.
The goal of this approach is to provide effective treatment while minimizing long-term exposure to the medications. However, treatment duration may vary depending on specific clinical scenarios, physician recommendations, and patient response to therapy.
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Logged in:
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Prompt: Is acalabrutinib plus obinutuzumab a fixed duration therapy?
In summary, acalabrutinib plus obinutuzumab can be used as fixed-duration therapy, but the exact duration will depend on the individual treatment plan.
Yes, acalabrutinib plus obinutuzumab is generally considered a fixed-duration therapy when used for chronic lymphocytic leukemia (CLL). In clinical trials, such as the ELEVATE-TN study, this combination was administered for a defined period:
Obinutuzumab is given for six cycles (each cycle is 28 days).
Acalabrutinib is typically continued until disease progression or unacceptable toxicity.
While acalabrutinib monotherapy is often used as a continuous treatment, the combination with obinutuzumab is sometimes considered for a time-limited approach, depending on treatment goals and patient factors. Always consult a hematologist or oncologist for personalized treatment planning.
-----
The ELEVATE-TN trial Design Details say:
"Experimental: Arm B - Acalabrutinib in Combination with Obinutuzumab
Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles starting at Cycle 2 Day 1. Acalabrutinib (ACP-196) will be orally administered starting on Cycle 1 Day 1. Daily administration of Acalabrutinib (ACP-196) will continue until disease progression or unacceptable toxicity."
As you can see, it still lied about ELEVATE-TN being fixed duration.
It was nice that it added "Always consult a hematologist or oncologist for personalized treatment planning."
As far as AI improving, I agree, with the caveat that it can regress unpridictably in particular cases. I think the newer versions have better grammar parsing, and may check answers a little more. But given the task of being able to answer any question given truthfully is still too much to ask. It is Dunning-Kruger codified.
"The Dunning–Kruger effect is a cognitive bias in which people with limited competence in a particular domain overestimate their abilities."
The fear from a marketing standpoint is that if it doesn't sound sure, people won't trust it. So we're being fooled into trusting an inherently untrustworthy advisor.
If I were younger, I'd certainly have a subscription, and aim for a job using and advising in the use of AI. It's come a long way from the 1980s when I first saw demonstrations of Expert Systems using LISP and Prolog. and the chatbot, Eliza. But it's like a teenager - a lot of strength, some good brains, but too little experience to handle nuanced situations.
Maybe you just asked the wrong LLM. ChatGPT, no argument or prompts required. ChatGTP responses in italics.
Q: Is acalabrutinib plus obinutuzumab a fixed duration therapy?
No, acalabrutinib plus obinutuzumab is not considered a fixed-duration therapy.
Duration of Therapy:
Obinutuzumab (anti-CD20 monoclonal antibody) is given for a fixed duration (typically 6 cycles, ~6 months).
Acalabrutinib (a Bruton's tyrosine kinase [BTK] inhibitor) is taken continuously until disease progression or unacceptable toxicity.
Fixed-Duration vs. Continuous Therapy:
Fixed-duration therapies in CLL typically involve fixed-duration regimens, such as venetoclax plus obinutuzumab (VO) for one year or venetoclax plus rituximab (VR) for two years.
BTK inhibitors like acalabrutinib (or ibrutinib) are continuous therapies because they do not induce deep remissions like venetoclax-based regimens.
Conclusion:
Acalabrutinib plus obinutuzumab is NOT a fixed-duration therapy because acalabrutinib is continued indefinitely, unlike venetoclax-based regimens which have a defined stopping point.
= - = - = - = - = - =
Try a 2nd question about CLL genetics, here is some info from CLL14 genetic data.
76% del(11q) are U-IgHV
59% SF3B1 are U-IgHV
80% del(11q) + SF3B1 are U-IgHV
Q: What is likely IgHV mutation status of a CLL patient with del(11q) and SF3b1 mutation?
In chronic lymphocytic leukemia (CLL), the IGHV mutation status is an important prognostic marker. Patients with mutated IGHV generally have a more favorable prognosis, while those with unmutated IGHV tend to have more aggressive disease.
Considering del(11q) and SF3B1 Mutation:
1. del(11q):
Associated with ATM gene deletion, leading to defective DNA damage response.
More common in younger patients and linked to more aggressive disease.
Often correlated with unmutated IGHV.
2. SF3B1 Mutation:
Frequently found in unmutated IGHV CLL.
Associated with more rapid disease progression and resistance to chemotherapy.
Present in approximately 10-15% of CLL cases, often linked to high-risk disease features.
Conclusion:
Since both del(11q) and SF3B1 mutations are more commonly associated with unmutated IGHV, it is highly likely that this CLL patient has an unmutated IGHV status. However, direct sequencing of the IGHV region remains the definitive way to confirm the mutation status.
I just tried the same query a few minutes ago at chatgpt.com/ , and got:
Prompt: Is acalabrutinib plus obinutuzumab a fixed duration therapy
Yes, the combination of acalabrutinib plus obinutuzumab is typically considered a fixed-duration therapy in certain contexts, particularly for chronic lymphocytic leukemia (CLL). In clinical trials, this combination has been used as a fixed-duration regimen where patients receive the treatment for a set period (e.g., 12 months) rather than continuing therapy indefinitely.
The goal of this approach is to provide effective treatment while minimizing long-term exposure to the medications. However, treatment duration may vary depending on specific clinical scenarios, physician recommendations, and patient response to therapy.
----
I then logged into ChatGPT (I got a free account in 2023):
Prompt: Is acalabrutinib plus obinutuzumab a fixed duration therapy
In summary, acalabrutinib plus obinutuzumab can be used as fixed-duration therapy, but the exact duration will depend on the individual treatment plan.
Yes, acalabrutinib plus obinutuzumab is generally considered a fixed-duration therapy when used for chronic lymphocytic leukemia (CLL). In clinical trials, such as the ELEVATE-TN study, this combination was administered for a defined period:
Obinutuzumab is given for six cycles (each cycle is 28 days).
Acalabrutinib is typically continued until disease progression or unacceptable toxicity.
While acalabrutinib monotherapy is often used as a continuous treatment, the combination with obinutuzumab is sometimes considered for a time-limited approach, depending on treatment goals and patient factors. Always consult a hematologist or oncologist for personalized treatment planning.
Was all the text after the Conclusion, such as data from CLL14 and IGHV results part of its response? CLL14 did not test Acalabrutinib plus Obinutuzumab.
That changed the response but it's still telling me the right answer.
Q: Is acalabrutinib plus obinutuzumab a short duration therapy? give sources
ChatGPT said:
As of February 2025, the combination of acalabrutinib plus obinutuzumab is not typically administered as a fixed-duration therapy for Chronic Lymphocytic Leukemia (CLL). In standard clinical practice, acalabrutinib is prescribed for continuous use until disease progression or unacceptable toxicity, while obinutuzumab is given for a fixed duration, usually six cycles over approximately six months. This results in a regimen where obinutuzumab is time-limited, but acalabrutinib continues indefinitely.
However, recent clinical trials have explored fixed-duration regimens involving acalabrutinib in combination with other agents:
Acalabrutinib plus Venetoclax, with or without Obinutuzumab: The AMPLIFY Phase III trial investigated these combinations as fixed-duration therapies for previously untreated CLL patients. Results demonstrated a significant improvement in progression-free survival (PFS) compared to standard chemoimmunotherapy. Specifically, the triplet combination (acalabrutinib, venetoclax, and obinutuzumab) reduced the risk of disease progression or death by 58% versus standard care.
These findings suggest that while acalabrutinib plus obinutuzumab alone is not currently a fixed-duration therapy, ongoing research may influence future treatment protocols.
Here are key clinical trial findings related to acalabrutinib plus obinutuzumab and its potential as a fixed-duration therapy:
1. Current Standard of Acalabrutinib + Obinutuzumab
According to a 2021 review in American Journal of Hematology (PMID: 34625994), acalabrutinib is generally used as continuous therapy until disease progression, while obinutuzumab is administered for a limited duration.
However, clinical trials are exploring fixed-duration combinations of targeted therapies, including BTK inhibitors like acalabrutinib.
2. Evolving Fixed-Duration Strategies
A 2024 review in Current Hematologic Malignancy Reports (PMID: 38337108) discusses ongoing efforts to develop time-limited approaches, including combinations of BTK inhibitors (like acalabrutinib) with venetoclax or obinutuzumab.
Venetoclax-based regimens (e.g., venetoclax + obinutuzumab) are already well-established as fixed-duration therapies.
3. Clinical Trial of Acalabrutinib + Venetoclax + Obinutuzumab as Fixed-Duration Therapy
A 2021 Phase 2 study published in Lancet Oncology (PMID: 34534514) investigated acalabrutinib + venetoclax + obinutuzumab as a fixed-duration regimen in treatment-naïve CLL patients.
This trial used Minimal Residual Disease (MRD)-guided discontinuation, with treatment stopping at 16 or 25 cycles if MRD was undetectable.
Results showed high response rates, but the primary endpoint (complete remission with undetectable MRD) was not met.
4. Future Directions
A 2022 review in Blood Reviews (PMID: 35151528) highlights that time-limited BTK-based regimens are actively being studied.
Trials are evaluating whether fixed-duration BTK inhibitor regimens can achieve deep remissions and avoid the need for indefinite therapy.
Conclusion
Acalabrutinib + obinutuzumab alone is still a continuous therapy, but research is ongoing to determine if it can be used in a fixed-duration approach.
Combination regimens like acalabrutinib + venetoclax + obinutuzumab are being tested in time-limited strategies.
The decision on fixed vs. continuous treatment depends on clinical trial outcomes, MRD status, and individual patient factors.
Would you like a deeper dive into a specific trial or ongoing studies?
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PubMed Buddy is a nice tool, but it only asks for abstracts, and may miss nuances the authors only discussed in the full paper. It's a research tool. One can grab the pmid IDs and get to full free text, or if at a medical library with subscription, paywalled info.
I'm not sure if regular ChatGPT was trained with PubMed data. I hope so, even though even PubMed has controversial papers. If it uses PubMed, I don't know what weight it gives the results compared to, say, MedPage.com or Mayo.org or any other standard medical web resource.
I couldn't resist seeing whether AI learns from its errors and inconsistencies..
I just asked the following questions. ( I won't include the full responses and references.)
1. Is it true that Acalabrutinib + Obinutuzumab is a fixed-duration therapy for CLL? Please provide appropriate and genuine references to support your response.
ChatGPT said:
Yes, it is true that the combination of acalabrutinib and obinutuzumab (AVO) is considered a fixed-duration therapy for chronic lymphocytic leukemia (CLL). In the ELEVATE-TN trial, patients received acalabrutinib at 100 mg twice daily for 14 cycles, with obinutuzumab administered intravenously at 1000 mg during cycles 2 through 7. This regimen was designed as a fixed-duration treatment, with therapy concluding after the specified cycles, regardless of disease status.
Me: Someone else asked the same question of ChatGPT yesterday. ChatGPT's answer was "No, acalabrutinib plus obinutuzumab is not considered a fixed-duration therapy." The conclusion was "Acalabrutinib plus obinutuzumab is NOT a fixed-duration therapy because acalabrutinib is continued indefinitely, unlike venetoclax-based regimens."
ChatGPT said:
You're correct that there seems to be some inconsistency. Let me clarify the situation.
Acalabrutinib + Obinutuzumab (AVO) can be considered a fixed-duration therapy in some clinical contexts, but the key factor is how the treatment regimen is structured.
• In the ELEVATE-TN trial: Acalabrutinib was combined with obinutuzumab as part of a treatment regimen with a fixed duration of therapy. The treatment lasted for a specified number of cycles (14 cycles of acalabrutinib, with obinutuzumab given during cycles 2 to 7). This makes the regimen a fixed-duration approach for those particular patients in this trial.
• However, it's true that acalabrutinib by itself is typically a continuous, indefinite treatment, as it's a Bruton's tyrosine kinase (BTK) inhibitor. This makes it different from regimens like venetoclax-based therapies, where the treatment is typically designed to be fixed-duration, meaning patients stop after a certain number of cycles.
To summarize:
• Acalabrutinib + Obinutuzumab can indeed be given as a fixed-duration therapy when it's part of a protocol designed for a set number of cycles (as seen in the ELEVATE-TN trial).
• Acalabrutinib alone, though, is usually given indefinitely, which is why it’s often seen as a continuous therapy.
So, while Acalabrutinib + Obinutuzumab can be part of a fixed-duration therapy, this might not be the case in all settings. It largely depends on the specific clinical protocol and how the treatment regimen is structured.
2. If I had a paid subscription to ChatGPT would I be assured of the right answer to my question?
ChatGPT said:
A paid subscription to ChatGPT (such as the "ChatGPT Plus" plan) offers access to the more powerful GPT-4 model, which provides more accurate and nuanced responses. However, even with GPT-4, there can be occasional inconsistencies or variations in the answers provided, especially when it comes to complex or evolving medical information.
While GPT-4 can generally give more accurate and context-aware responses compared to GPT-3, it’s still crucial to verify specific medical information from trusted clinical guidelines, peer-reviewed research, or consult a healthcare professional directly.
So, while a paid subscription might improve the quality and reliability of the answers, it doesn’t guarantee perfection in every case. You’re always encouraged to cross-check medical information from primary sources like clinical trials, medical journals, or healthcare providers.
Have you tried DeepSeek? You should try it for comparison. I recommend you tell it you're a world expert in blood cancer, that sets the complexity level of response. Then ask your question.
This AI bot is a lot more sophisticated than ChatGPT. It's not surprising that silicone valley & the markets went into panic mode.
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Adding Venetoclax to Obinutuzumab Prolongs Progression-Free Survival in Previously Untreated CLL
AbbVie Pharm--positive phase 3 for CLL!
