CLL 17p - Rituximab/Imbruvica then Rituximab/Venetoclax or enter in a clinical trial ?

[Noham027]

First of all I would like to thank you for responding to my previous post... It really helps me !

My mom had an appointment last Thursday 27th in another hospital to see if she could be included in the following clinical trial: "A phase 3 multicentre, randomized, prospective, open-label trial of ibrutinib monotherapy versus fixed-duration venetoclax plus obinutuzumab versus fixed-duration ibrutinib plus venetoclax in patients with previously untreated chronic lymphocytic leukaemia (CLL)"... (it should be ok but we wait for a response...probably next week)

Last Tuesday and Friday, her current hemato - who's aware of the above trial - advises her to take rituximab + ibrutinib and then switch to veneto + ibrutinib in September... Her hemato said ''proceed in a sequential manner can also give her a chance to reach a mrd...but you have to choose ''.

So now she is a quite lost because on one hand she wants to stay with her current hematologist by habit/facility (I think)... And on the other hand she understood that veneto + ibru or veneto + obi would be more efficient in her case... But she could also not benefit from it and simply 'fall' on ibrutinib in monotherapie... So she is asking me if it is not safer to stay with the current hemato and have ritux+ibru and then veneto + ritux in September... Than to take the ''risk'' to enter in the trial...

We are in a phase where my mom is taking medrol to stabilise her condition as red blood cells have decreased to 10,5g/dL and she cannot start any treatement otherwise she would not access to the trial... the current hemato would like to give her ritux asap (apparently 6 hours in the hospital the first time...)

I would like her to have the best treatement but i'm aware it is difficult to know in advance ... May I please ask you What would you do/advise in my place... ?

I don't know what the ritux + ibru treatment worth neither veneto + ritux... I still have to look/read studies/feedback on it...

Thank you very much in advance

Noham

[bennevisplace]

One thing to bear in mind is that a patient in a clinical trial is entitled to withdraw at any time.

[cajunjeff]

Noham, I am not a doctor or Cll expert, but I am well read on the treatment options you are describing. I also have a decent understanding about the pros and cons of clinical trials. Here are my thoughts.

Clinical trials come in all shapes and sizes. In the one your mom is being offered, she would be randomly assigned to one of three arms of the trial. All three arms are reasonable choices, but if I had to pick one, it would be the venetoclax /ibrutinib arm.

Venetoclax and ibrutinib is basically what your mom is being offered outside the trial, just in a different sequence. The treatment outside of the trial starts with ibrutinib and Rituxumab. These two drugs would not likely put your mom in remission, but they would very likely “debulk” her Cll, meaning lessen her tumor load, tumor load meaning the amount of Cll in her blood and lymph nodes.

It sounds like after “debulking”, venetoclax would be added. This makes sense because venetoclax is a very powerful drug that can be dangerous to take when one has a high tumor load because it kills Cll cells so rapidly, one can get very sick in the process of expelling the dead cells. That is called tumor lysis syndrome. That is one reason some doctors choose to sequence ibrutinib and venetoclax.

Doctors in clinical trials have much less flexibility to change a treatment plan based upon how a patient is doing or upon newly discovered therapies. Outside of a clinical trial, doctors have much more flexibility to add and subtract drugs as they watch their patients in real time.

Since I would choose the ibrutinib/venetoclax arm of the trial anyway, it would be an easy choice for me. I would pick ibrutinib and venetoclax outside of the trial because I know I would get it and not be randomized to another arm. As important or more important, if your mom is treated outside of a trial, her doctor is not bound by the rules of the trial and has more flexibility to treat her.

Trials often come with other rules like more bone marrow biopsies and ct scans that might normally be necessary.

But there are many reasons, depending on the trial and where someone lives, to pick the trial. Clinical trials can provide expensive drugs people might not otherwise afford for free. I think the increased monitoring you get in a trial can be a good thing. Some drugs are not even available to people in some countries outside of a clinical trial.

Your mom is fortunate to have two good choices. I personally would pick the venetoclax and ibrutinib option outside of the trial which would allow her doctor more ability to change course. I am not sure what additional benefit is achieved by adding Rituximab, but it might help and probably would not hurt.

You are a good son for helping your mom. Good luck with whatever choice you and she make.

[thompsonellen]

I am 17p deleted and I recall my doc, Dr. Byrd (top tier doc who worked on developing rituximab) told me rituximab is not a solution for us because we are resistant to this treatment. Here is an article that also mentions that, but confirm with others. jitc.biomedcentral.com/arti... Personally, I did the obinutuzumab, venetoclax, and ibrutinib trial. 5 years later, I'm still on ibrutinib. At the time, the first doctor I saw recommended ibrutinib monotherapy and I stopped seeing him after he told me I was crazy for doing the trial. Hope this helps.

[attarintiki]

Hello Noham027,I can understand your dialama for decision making. I am sorry as I am not able to help by suggesting the right therapy. I had only 2 cycles of Bendamustine + Rituximub. Fortunately the 2 cycles helped me as I am in remission since 2019. I believe my colleagues in the form will share theor experiences. Best of luck.

[Catnap7]

Hi Noham027I took the Ibrutinib/Venetoclax 2 year trial and so grateful I did.

Upon entering the trial I think I was up around 90%

in the bone marrow. Not good !!! They had my back all

the way through. I felt like they rolled out the red carpet

and did everything to make sure I didn't slip through any cracks.

If anything did come up they were immediately there to take care

of my problem. I even had a trial nurse I could text. She would ask

the doctor and get back with me sometimes in 30 minutes.

They DID adjust my drugs during the trial... they actually lowered

the dosage. Why would one take I/V out of trial if they could do it

in trial and redeem all the perks including monetary perks?

My numbers 17 P deletion 11 q and others were not good.

I got UMRD one year in... These were the right drugs for me

I now look back at the time I was making my decision to do the trial.

It makes me laugh a little as the TRIAL for me was not only right

but the best decision I have ever made in my life

Best to you Noham027 !!!

Catnap 7