Venclexta mono therapy vs Venclexta plus gazyva

[ralphfelo]

I was treated with Ibrutinib for five years until resistance developed.Following with venclexta mono therapy for about a year, stopped due to pandemic.

Remission lasted 2 years and now I am faced with a choice that has me very worried.

One doctor at City of Hope wants to do venetoclax monotherapy starting at low doses. His reasoning is that since I have a tendency to neutropenia Gazyva would not be well tolerated. Also he explains that the hematological side effects would last a long time after Gazyva treatment is stopped.

The other Dr at UCI recommends venetoclax and Gazyva per the trial plan.

I worry that venetoclax monotherapy would eventually lead to resistance with limited or no optiond at that time.

I follow all your posts and stories and feel you are a knowledgeable group with great empathy.

I would appreciate any of your comments.

Best to all of you

Ralph

[AussieNeil Administrator]

Hi Ralph,

I agree with you regarding your concern about developing resistance to venetoclax when used as a monotherapy, given you've developed resistance to the covalently bonding ibrutinib. This means that acalabrutinib and zanubrutinib (also covalent bonding BTKis) are also unlikely to work. Pirtobrutinib (being a non-covalent bonding BTKi) is likely to work for at least a while, but it's currently only available for CLL off label, or through a clinical trial. CLL specialists have been recognising this unmet need for a while now, when we've developed resistance to both BTKi (the 'brutinibs') and BCL-2 therapies (venetoclax). Venetoclax + obinutuzumab treatment does come with the ability to repeat it as needed if your remissions last long enough. That your last remission lasted two years after a year of venetoclax treatment is, I would think, encouraging in this regard.

That said, your doctor worried about you developing neutropenia with obinutuzumab has a point - but venetoclax too has a reputation for doing so and the obinutuzumab infusions are over in 24 weeks. Obinutuzumab typically does prevent you from developing antibodies from infections and vaccinations for at least a year, plus there's a risk of developing late onset neutropenia during this period, particularly if you have had G-CSF injections to boost your neutrophil count to get you through the infusions. If you need to mix socially or for employment, then venetoclax monotherapy might be a better option.

With regard to your "tendency to neutropenia", I underwent treatment of V+O combined with acalabrutinib. I'd had chronic neutropenia all during watch and wait - averaging a neutrophil count of 1.0 over the 11 years I was in W&W. I nearly didn't make my clinical trial criteria of achieving a neutrophil count over 0.5 after a week off G-CSF injections and after starting the trial, needed G-CSF shots up to daily until I started my obinutuzumab infusions, after which my bone marrow recovered sufficiently so that I no longer needed the G-CSF shots. I sailed through the venetoclax ramp-up with no need to hold the dose while my neutrophil count recovered. The pandemic hit just after I began my obinutuzumab infusions. I've been extremely careful to reduce my risk of infections, in particular COVID-19 since then, wearing an N95 (PPF2) mask whenever appropriate and have managed to avoid any serious infections. We are all different, so my experience is no guarantee that you'll have the same success. but I hope you do.

Neil

[ralphfelo in reply to AussieNeil]

Thank you Neil for your thoughtful and helpful reply.It is a difficult choice to do one or both but I am encouraged by your results. I am 76 and have to factor in the age for tolerance to the dual treatment and also even if lucky basically giving up one of the years left in my life.

I sincerely thank you for sharing your experience, it was helpful and also comforting that you took the time to reply, it makes me feel a little less alone with this.

All the best for you

Ralph

[charliegirl]

Dear Ralph

I've been down a similar path. Started on ibrutinib in 2014. Stopped 2017 because of peripheral neuropathy, not resistance. Started venetoclax monotherapy 2018 (no combinations in use at that time). I had problems with neutropenia;therefore maintained on 300mg daily together with G-CSF injections once or twice weekly throughout. With this regime treatment was not time limited and so I stayed on it for nearly 3 years.

I had to stop treatment in Spring 2021 when I developed a very low platelet count. This turned out to be ITP due to Covid vaccinations and not venetoclax.

I then stayed off treatment until last autumn. I then had to restart venetoclax plus rituximab x 6, four weekly infusions (obinutuzamab not used for secondary venetoclax treatment).

I have now completed rituximab and continue venetoclax, albeit at 200mg daily. Different haematologist more cautious re dosage. I'm also having G-CSF weekly for neutropenia again and this is well controlled. Rest of blood count also v steady.

I was not offered monotherapy with venetoclax this time, despite the various cytopenias, and thought that this wasn't now usually considered because of greater risk of developing resistance.

I'm in the UK

I am 75 .

Good luck with your treatment

Charlie Girl

[Thundercat2]

I read your post and although I don't have a lot to add to the replies I wanted to offer a word of support. I'm glad you posted and hopefully found some good information to move forward in your decision. It can be a lonely place living with all of this but fortunately we have this site to help us. And there are still new treatments in the pipeline.

I was on Venetoclax and Obinutuzumab and although it was a bit time consuming at the start it's not really as bad as it sounds. There is much time in between where life goes on pretty much as normal.

Wishing you the best