Dr. O'Brien on how she treats CLL frontline an... - CLL Support

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Dr. O'Brien on how she treats CLL frontline and Dr. Pagel on new ways to block BTK

bkoffman profile image
bkoffmanCLL CURE Hero
12 Replies

Hi,

In frantic mode heading to ASH. We had our poster accepted about research on our own free Expert Access Program. More on that later.

If you have burning questions for the researchers, please let me know.

But first, some news from EHA earlier this year. So much CLL news in 2019. Still have a few more to report from EHA and a very brief top 10 from ASCO.

•At EHA 2019, Dr. Susan O’Brien explains how she decides what is the best front line treatment option for her CLL patients. cllsociety.org/2019/11/eha-...

•At EHA 2019, Dr. Pagel discusses new ways being researched to block BTK in CLL (chronic lymphocytic leukemia). cllsociety.org/2019/11/eha-...

Stay strong.

We are all in this together.

Brian

Brian Koffman MDCM (retired) MS Ed

Co-Founder, Executive VP and Chief Medical Officer

CLL Society, Inc.

cllsociety.org

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bkoffman profile image
bkoffman
CLL CURE Hero
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12 Replies
caven profile image
caven

Dr. Brian Koffman, Medical Director of the CLL Society, was in a hurry when providing this post. He didn't include the important digest to the video clip which he produced as a summary of the comments from Dr. Susan O’Brien's interview. The full commentary is posted at: cllsociety.org/2019/11/eha-...

I've clipped the pertinent points below.

+++++++++++++

Dr. Susan O’Brien moved from MD Anderson to head up the CLL research and clinical team at the University of California at Irvine (UCI), and we chronic lymphocytic patients in southern California are happy to have her.

She is a powerful advocate on our behalf and a smart clinician who carefully considers the best options for the patient in front of her.

In this interview from EHA (European Hematology Association) Annual Congress held in Amsterdam in 2019, she shared her strong opinion on how CLL should be managed frontline.

Takeaways:

* FCR may still have a role in young healthy patients with mutated IGVH and no other poor prognostic factor, but it is only for a very small select group of CLL patients. For those patients, more than half may be cured of their CLL with only 6 months of therapy.

* O’Brien sees no role for Bendamustine and Rituximab (BR) in treating CLL. There is no data to suggest some patients are cured.

* For most patients, a novel agent is the best choice.

* The decision comes down to a choice between the two approved frontline options using novel agents, namely ibrutinib and much more recently venetoclax plus obinutuzumab (V+O).

* 5-year survival on single agent ibrutinib has > 80% survival based on the data from the Resonate 2 trial.

There is no similar long-term robust data for V+O, but it is appealing for a number of reasons:

* Treatment is fixed duration lowering cost and even more importantly, perhaps lowering the risk of developing resistance.

* Many patients are reaching levels were their CLL is undetectable (U-MRD or undetectable minimal residual disease). This rarely happens with single agent ibrutinib.

* There are some patients now several years out on venetoclax who continue to do well.

* There is less data for 17p del frontline as only 5-7% have 17p del before chemotherapy but it seems response rates are nearly as robust for both treatment options as they are for those without it, so the presence of 17p deletion or TP53 doesn’t really help guide therapy.

Clinical trials are always a good option when appropriate.

Conclusions:

What is clear from this interview is that for nearly all patients, chemo should be off the table and that for each and every patient, BR should not be an option. There is proof that we have better therapies!

Caven

cllady01 profile image
cllady01Former Volunteer

I feel the need to Caution our members in regard to treatment availability.

However, that chemo for most should be off the table, we have an international support membership and some of the novel treatments are yet to be available. That is unfortunate and needs to be taken into consideration when attempting to help a member asking about what is their best treatment.

Newdawn profile image
NewdawnAdministrator in reply tocllady01

Agree cllady and certainly in the U.K., NICE (National Institute for Clinical Excellence) remain to be convinced that ‘chemo should be off the table’ because it remains the first line option for CLL in the absence of TP53/17p deletion regardless of hyper mutation status (outside of a Trial).

It’s clearly highly valued, informative data that can influence future funding decisions but as cllady says, this is an international site where health resources are not created equal.

I was also somewhat surprised to hear the expression ‘cured’ as opposed to ‘in remission’ used in this article.

Newdawn

cllady01 profile image
cllady01Former Volunteer in reply toNewdawn

Newdawn, I wish I could disagree in regard to "cure" being used, but from everything we have seen, it is too early for that to be stated. We all wish for it to be so and hope for it to be so very soon. But, there is not a way to move the treatments and trials faster and it is only time that will tell the tale.

bkoffman profile image
bkoffmanCLL CURE Hero in reply tocllady01

There is disagreement among well meaning reputable CLL experts about the role of chemo. There is even a debate at ASH pro and con on the role of chemo-immunotherapy frontline in CLL. My personal opinion is that outside a clinical trial or for a healthy young mutated patient or where you have no other choice, there is no role for chemo. My opinion.

cllady01 profile image
cllady01Former Volunteer in reply tobkoffman

Thank you for that statement, Dr. Koffman.

bkoffman profile image
bkoffmanCLL CURE Hero

There is strong disagreement among well meaning reputable CLL experts about the role of chemo. There is even a debate at ASH pro and con on the role of chemo-immunotherapy frontline in CLL. My personal opinion is that outside a clinical trial or for a healthy young mutated patient or where you have no other choice, there is no role for chemo. My opinion, shared by many experts, but certainly not by all.

Smakwater profile image
Smakwater

Fascinating and Exciting News!

Reversible and non binding? Cell programming?

Whats next, a choice of flavors?

JM

bkoffman profile image
bkoffmanCLL CURE Hero in reply toSmakwater

Is purity of BTK inhibition best or does blocking ITK help?

Smakwater profile image
Smakwater in reply tobkoffman

I'll take one of each.

sllincolorado profile image
sllincolorado in reply tobkoffman

Dr. Koffman - do you have a general opinion as to whether someone doing well on a BTK inhibitor should add O+V or if they should hold off as a fix if the inhibitor fails? Someone with all the bad markers (17p, unmutated, etc.). I realize that everyone has a different situation and there is likely not one right answer.

bkoffman profile image
bkoffmanCLL CURE Hero in reply tosllincolorado

Generally I would leave well enough alone but for folks with high risk disease like you I see real advantages to adding V (less so Obin) , getting to U-MRD and then stopping everything. Just my opinion

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