Surprise with obinutuzumab + venetoclax treatment

[simsorok]

Hi all. I would like to briefly tell my story of HLL and ask for advice from the participants of this wonderful forum.

The disease was diagnosed in 2008. I was under observation for 12 years. In addition, maybe because of CLL, I developed kidney failure.

In 2020, the decision was made to start treatment with obinutuzumab + venetoclax due to: very large spleen; wbc - 175; hgb - 10.5.

However, after the first intake of obinutuzumab and a few days after it, the volume of the spleen dropped sharply down to the normal state, blood parameters also changed dramatically: wbs - 2.0; hgb - 11.2.

The doctor called these sudden changes dramatic and dangerous. Obviously, he meant that I was close to tumor lysis syndrome - TLS.

In connection with these abrupt changes, the doctor decided to stop the treatment.

Over the next two years after trying the treatment, my performance gradually worsened. Again, significantly, almost as before, the volume of the spleen increased, but the blood was better wbc - 57.0; hgb - 13.1.

Now my doctor suggests starting treatment with ibrutinib (after all, there was an unacceptable reaction to O + V).

Now I would like advice on whether it is worth delaying the treatment because I feel good even after omicron, there are no night sweats and obvious weakness, and the blood counts are not extreme ... Any opinions on this matter, please.

All health and spiritual strength.

[lankisterguy Volunteer]

Hi simsorok,

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We like to help, but providing medical opinions, especially when they disagree with your doctor is something we cannot do.

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But assuming you are in the USA ( you didn't disclose that when you joined us in April 2022), you may be able to get a free medical opinion from a CLL expert, by video by signing up here:

cllsociety.org/programs-and...

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In my own case, I was on Venetoclax for almost 6 years and reached MRD-U (Minimal Residual Disease- UnDetectable or UnMeasurable) two times, but my recent results showed that Venetoclax was no longer doing the job. My doctor started me on Calquence / Acalabrutinib in January 2022 and my MRD results went from 1.3% to 0.07% in April 2022. I will be stopping Venetoclax shortly and my doctor plans to keep me on a BTKi ( Ibrutinib, Acalabrutinib, Pirtobrutinb) for as long as that family works well.

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Len

[SofiaDeo]

I agree with lankisterguy, and will also add that I wonder if you possibly misunderstood something going on with your symptoms or labwork. To think your doc stopped an O&V treatment intitiation based on what you reported, it doesn't make sense to me. Even IF tumor lysis syndrome was suspected, there are protocols to manage. So I would hazard a guess there is something else going on for a doc to say "this is dramatic and dangerous". It's not "obviously TLS" IMO. If you search other posts here, there are numerous reports of the well-known, not unexpected, things that can happen during obinutuzumab initiation, as well as the various strategies used to manage the different reactions. Offhand I can't think of anyone here reporting a decision to not continue, based solely on a suspected TLS. Premeds were adjusted, rate of infusion was adjusted, but no one stopped based solely on suspected TLS (or even the well-known "infusion reactions"). So that's why I wonder if something else happened.

If the nurses/docs starting this protocol were not experienced ICU staff, or if these weren't done in a clinic with crash cart and surgery/ICU support, I can see where large molecule infusion related reactions would seem alarming, "dangerous". If they don't have a lot of experience treating infusion reactions, or correct monitoring and support services readily available, that could be interpreted as "dangerous". But these are actually common, expected, and there are well known protocols in the literature of how to manage these.

[Big_Dee in reply to SofiaDeo]

Hello SofiaDeo

I agree, something else may be at work here. Before I started my B+R treatment, I asked my doctor if I would need to combat tumor lysis syndrome and she said no need. First 10 days post first treatment, I went from 200K WBC to 16k and rest of bloods normalized without any tumor lysis syndrome.

[SofiaDeo in reply to Big_Dee]

And I started Venclexta with only a little over 100K, and was kept in the hospital longer than anticipated, almost started on phosphorous lowering meds, due to elevated PO4 and some changes in renal parameters. I only had a single large internal node, but my spleen was a large 24cm. I was very happy my CLL specialist was conservative and hospitalized me, because high PO4 can damage kidneys without symptoms. It was worth the inconvenience and $$ to keep on top of things.

So I wonder if cllady01's observation that you have a history of kidney problems, were related to what your doc said & did.

[cllady01 Former Volunteer]

It may help you to ask your Dr. to let you see all tests results. And to ask that you be given reasons for needing to treat at this time. You can be a part of the decisions made if you have more information to help you to take part in discussions with your Dr.

If that doesn't work, I second the suggestion by lankisterguy. A second opinion by a CLL expert is the way to go for your peace of mind.

It will take action on your part and getting your test information to the expert for review, but that is time that is well spent when you will have a more definitive answer for the need of treatment for your CLL.

I wonder if what happened with Obinutuzumab was not TLS, but had to do with your kidney failure, as you may not have seen the results of all the tests that are taken to monitor what is happening with the changes the treatment produces. The Comprehensive Metabolic Panel for seeing how your organs are working with the treatment is an important part of the monitoring of your treatment. Ask about seeing those reports.

Best wishes, and please let us know how you are doing with whatever the process.

We do want to support you and help you to advocate for yourself and be a partner with your Dr.

[NaturalWaze]

I agree with the second opinion, and question that the obinutuzimab reaction was “unacceptable.” Because of the risk of TLS, my dr does the first treatment in the hospital, where she closely monitors and gives IV liquids to flush the kidneys. I ended up being there for 8 days (due to fevers).Good luck to you,

NW

[spi3]

Please ask for a second opinion--all replies to your request have been spot-on. Everyone's body is different and each CLL is different too. For us, my husband's kidneys were failing - his Dr provided him IV liquids and other protocols and once stable he was given his treatments. The Dr directed to drink lots of water (a certain percentage) to help with the medicine and his kidneys. It sure has helped him a lot to tolerate his treatments.

[Tapps]

My husband had GAZAYVA and the Chemo pills. Major reaction to the first day of GAZAYVA, put in the hospital with the Chemo pill, stopped those. Finished the GAZAYVA treatment. Lasted five years. At that time Ibrutinib was not authorized for first line treatment.

2020 went on Ibrutinib, he is doing wonderful, no side effects at all. Be well my friend

[Tapps]

GAZAYVA and Obinutuzumab: are the same thing.

[simsorok]

Thanks to everyone who replies to my message. Health and cheerfulness friends.