Ibrutinib-Venetoclax is the recommended first-line therapy for fit Arab patients with CLL in the Gulf region

[CLLerinOz]

A group of CLL experts from across the Gulf region and an international expert from Germany have collaborated to agree upon a statement for the optimal first-line treatment of Arab patients in that region. The statement was released on 26 February 2025.

"Clinical management of CLL varies widely depending on patient profile, meaning the optimal treatment in Arab patients, who tend to be young and often present with comorbidities, including diabetes and obesity, requires specific considerations. In the absence of regional guidelines, a group of experts from across the Gulf region and one international expert from Germany convened to discuss and agree upon a position statement for venetoclax-based fixed-duration treatment strategies for Arab patients with CLL."

"Our position is that ibrutinib-venetoclax should be the first choice as first-line therapy for all fit CLL patients in the region, regardless of age. The advantages of an all-oral, fixed-duration treatment are discussed in the context of a young Arab patient population, including excellent patient and physician convenience, limited accumulative risk of toxicities, uncomplicated logistics, and low burden of healthcare administration costs. Finally, we discuss the management of key safety considerations in Arab populations including ethnic neutropenia, risk of cardiotoxic events, considerations during intermittent fasting, and avoiding adverse drug–drug interactions, e.g., with anti-tuberculosis or anti-obesity medications." (my emphasis)

The full paper can be found here: frontiersin.org/journals/me...

Yassin MA, Al Farsi K, Hamad A, Ghasoub R, Alhuraiji A, Mheidly K, Yaseen HA, Osman H and Trepel M (2025) Upfront fixed-duration treatment strategies for chronic lymphocytic leukemia in Arab populations: a position statement from the Gulf region. Front. Med. 12:1509074. doi: 10.3389/fmed.2025.1509074

Recently, Mazyar Shadman, Bita Fakhri and Nitin Jain published an article that highlighted the need for CLL guidelines to be responsive to local resources and patient populations. healthunlocked.com/cllsuppo... It's good to see this example of a recommendation that does that for those in the Gulf region.

Note: this is an unlocked post so anyone, even those outside our community, can read it. If you want to ask a question related to your own situation, it's advisable to start your own locked post. There's more information about locked and unlocked posts here: healthunlocked.com/cllsuppo....

CLLerinOz

[Kiwidi]

OMG! It makes a lot of economic sense. Obviously the Gulf States are wealthy but if you weigh up the other options in the long term it probably makes sense. We have been advocating for this in Aotearoa NZ but it seems it is not by any means a priority.

[CLLerinOz Administrator in reply to Kiwidi]

As the paper by Mazyar Shadman, Bita Fakhri and Nitin Jain stated "Unfortunately, availability, accessibility, and affordability are only true in a small number of countries, as access to nonchemotherapy CLL therapies remains very limited globally. Even when available, patients in many areas of the world may only have access to a limited selection of options, and the high cost of these drugs remains prohibitive."

In such settings, clinical trials become a very important way for those with CLL to access newer therapies but access issues can still prevent some from participating in a trial.

Right now, on clinicaltrials.gov, I can only see the following trial for front-line therapy listed as recruiting in NZ:

A Study of Nemtabrutinib (MK-1026) Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in First Line (1L) Chronic Lymphocytic Leukemia (CLL)/​ Small Lymphocytic Lymphoma (SLL) (MK-1026-011/​BELLWAVE-011) - recruiting in Auckland and Hamilton clinicaltrials.gov/study/NC...

In addition, the following trial is listed as 'active not recruiting' at a number of sites in NZ:

Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Participants With Chronic Lymphocytic Leukemia (CLL) clinicaltrials.gov/study/NC...

CLLerinOz

[Kiwidi in reply to CLLerinOz]

Thank you. I am keeping up with the trials available here. It is still not the same as having it funded as a first line treatment. I reckon you have to be ‘in the right place with the right numbers at the right time’ to access a trial.

[LeoPa]

Young, diabetic and obese with possible cardiovascular issues but otherwise totally fit. This struck me as a joke 🤣.

[Kiwidi in reply to LeoPa]

Mmm! But at least it sounds like most people have access to the combination! I wish that for all🤞everywhere.or at least an equivalent.

[LeoPa in reply to Kiwidi]

I suppose this is true for the rich states only, like the UAE, Qatar or SA, not Iraq, Iran and the other countries in the region.

[AshGS]

Good morning dear,

Thank you for the update. I have been only on Imbruvica for almost 3 years now and I have been informed by my doctor that I should remain on it for life time, unless there would be a relapse or any complications.

Now i see in the article that Ibrutinib-Venetoclax can be taken for a FIXED Duration.

So can you advise on the role of the Venetoclax and how this combined treatment is suffecient/effective for a FIXED Duration?

Thanks

[Skyshark in reply to AshGS]

The two drugs together work better than either alone. Used alone cBTKi drugs are taken continuously until intolerance or progression and Venetoclax (Ven) for 2 years. About 50% of patients have complete response and undetectable MRD by end of cycle 15 on Ven + Ibrutinib (about 14 months). Two key trials are CAPTIVATE FD and GLOW.

There is a current trial BRAVE (NCT06524375) that is adding Ven to cBTKi for patients that have had a response to a cBTKi and have been on cBTKi for longer than 6 months. Objective at end of 12 cycles of additional Ven is to halt treatment and have a drug free period of remission. Looking for 100 subjects but at present I only see recruitment in the US of A.

forpatients.roche.com/en/tr...

CAPTIVATE FD PFS at 4 years

[Bluesinthenight]

The difficult endpoint to assess is long term outcome - survival. With the targeted therapies given sequentially or in combination, this endpoint cannot be answered at this time. Time limited therapy such as with a combination has appeal for obvious reasons, but it remains to be determined if some people are better off with (1) continuous therapy, such as with a BTK inhibitor, or (2) combination therapy of a fixed duration, then re-treatment with something, either the combination or single agent, upon relapse. And to further complicate the survival endpoint will be newer agents that gain approval and will be used for future treatment.

[Canuck901]

that was a good combo 7 years ago , better combinations with venetoclax exist today .