Finished 1 year V&O

[jjaarons]

Started V&O last february after 6 years of watch and wait. Had profound fatigue at that time and work was difficult. In the beginning, I had one or two infusion reactions from the Gazyva but after that it went smoothly. I ramped up the venetoclax with no problem but at 400 mg per day may white count went below 1000 and I had frequent diarrhea. We did a dose modification to 300 mg per day and I was able to tolerate the regimen for the rest of the year. Now my white count is within normal range and my fatigue is somewhat better. My oncologist says remission should last 4-6 years but who knows. I am mutated and 13q. I had previous visits at Moffitt and MD Anderson before starting with similar evaluations and advice. Hard to argue when 3 doctors agree on the decisions. Hoping for a long remission. Seems like the choices for treatment are only improving at this time.

[lankisterguy Volunteer]

Hi jjaarons,

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That is a great write up and wonderful example of how to get good control of your CLL while dealing with some unwanted side effects. Please keep us appraised of your status, hopefully a long and uneventful PFS (Progression Free Survival).

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Len

[jjaarons in reply to lankisterguy]

Thanks. I will :))

[Palmetto in reply to jjaarons]

Inspirational. I hope husband does as well. However he is unmutated but is 13Q deleted. May you have a long PFS!

[jjaarons in reply to Palmetto]

Thanks

[DanBro1]

Just completed my O+V regimen March 1st. Same tolerance as you. I am in remission and my oncologist also commented at 4-6 years. It could go further, they just don't have the data to say longer.

[jjaarons in reply to DanBro1]

Thanks

[OmBewok]

Great to read your story. Thanks. I'm a bit behind you in my treatment. I started last November and will have my final Obinutuzumab infusion in about 2 weeks, after which I'll have another 6 months on Venetaclax. So far I've been very fortunate with no real side effects, apart from post-infusion fatigue for a week or so. It is great to read that you are in remission. I'm certainly keeping my fingers crossed for that outcome! Let's hope your oncologists are correct with their prediction. Best wishes.Om

[jjaarons in reply to OmBewok]

Thanks. I am sure you will have a great result.

[Aruk]

jjaarons - I am trying to decide if I should do V+O or ibrutinib. How bad was the immune compromised part of V+O ? Did you have to isolate a lot, be very careful about infections. I need to travel to my kid in college and elderly parents in a different state. So trying to determine best course of action given that.

[AussieNeil Administrator in reply to Aruk]

Obinutuzumab remains circulating in your blood after your last infusion, gradually being used up as it destroys new B cells entering the blood from your bone marrow. It can stay in circulation for up to at least a year after your last infusion. That means little to no antibody production response to vaccinations or infections.

[wellbeingwarrior in reply to AussieNeil]

AussieNeil, in comparison to 6 cycles of FCR.. how long does the immune system remain compromised after completing FCR, similar?

[AussieNeil Administrator in reply to wellbeingwarrior]

FCR - Fludarabine, Cyclophosphamide and Rituximab, is arguably worse with regard to its immune system impact than V+O. Rituximab/Mabthera and obinutuzumab/Gazyva, along with Ofatumumab/Arzerra are all anti-CD20 monoclonal antibodies. They all remain in the blood stream for up to a year or so after the last infusion, suppressing B cell recovery, so there's little opportunity for the development of antibodies from infections or vaccinations. Anti-CD20 monoclonal antibodies also come with a risk of what's termed Late Onset Neutropenia (LON). It's thought that when the bone marrow can again produce B lymphocytes, the competition for bone marrow resources can temporarily result in a drop in neutrophil production, so patients can potentially become severely neutropenic. Hence it's important to take precautions against infection for a year or more after treatment. LON is more likely if you've needed G-CSF shots during treatment to bring your neutrophils up to a sufficient level for your next infusion.

With FCR, there's also about a 10% long term risk of developing a secondary blood cancer - Acute Myeloid Leukaemia (AML) or Myelodysplasia or Myelodysplastic Syndrome (MDS) where the bone marrow struggles to produce blood cells. It can take up to two or more years for T cells to recover and other blood counts can also take a while to recover, some never make a complete recovery. Also, the older chemo treatments like FCR and BR (Bendamustine Rituximab, select for tougher to treat CLL sub-clones, with 17p del or mutated TP53, which can be tougher to treat.

While that sounds confronting, FCR was the undisputed gold standard treatment for about a decade until the arrival of ibrutinib. With the exception of a more risky bone marrow transplant, it's the only treatment that we know of which can arguable cure CLL. About 55% of IGHV mutated folk treated with FCR go on to have indefinite length remissions. Basically if you can make it to a 7 year remission, your subsequent likelihood of relapsing is very, very low. People who were treated in the early FCR clinical trials are now exceeding 20 years of remission. (We also know that unmutated IGHV folk shouldn't be treated with BR or FCR, because they aren't likely to have a long remission. Sadly, in many countries, you can't access a targeted therapy treatment for your first treatment. A growing number of countries are allowing the use of targeted therapy treatment for those who are 17p del or TP53 mutated, as these folk are unlikely to respond to BR or FCR - you need TP53 intact for the chemo affected CLL cells to trigger apoptosis.)

CLL specialists hope that the new combination targeted therapy treatments may also deliver indefinite remissions, with the bonus that there isn't the age restriction of 65 with FCR. With a median time of diagnosis for CLL of 70, followed by a median time to treatment of about 5 years, there are far more patients that could have long remissions after the newer treatments than there were with FCR. We just have to wait and see how long remissions last on combination targeted therapy treatments as they've only been trialed in the last 4 to 5 years.

Neil

[wellbeingwarrior in reply to AussieNeil]

So helpful, thank you Neil. I'm feeling a bit torn about it all and it's good to be able to source information from this site. 👍

When I was feeling better than I am now, I didn't really get too bothered and tried not to think too much about it. Now that there is greater burden of disease it's definitely taking up space in my brain as I contemplate and calculate and identify possible scenarios faced ahead.

[jjaarons in reply to Aruk]

Agree with AussieNeil. Obinutuzumab stays in your body and affects the immune system for about a year. I had COVID twice this year. No other infections. I always wear my mask and take precautions. That being said, I was happy that I was finished after a year. My oncologist says that it should last 4-6 years before additional treatment is needed. Ibrutinib has afib, hypertension and bleeding issues. I just read an article stating acalabrutinib has higher incidence of ventricular arrhythmias. No therapy is perfect. They each have their problems. I was happy with my choice.

[SofiaDeo in reply to Aruk]

If you are willing and able to take precautions, the immune compromised part shouldn't be overly risky like a standard chemotherapy would. Especially if you are making serum proteins/immune globulins, you can get this tested. Other components of your immune system should continue to work somewhat. I did a monoclonal antibody treatment that also affected T-cells in addition to lymphocytes, and didn't get any respiratory infections since I wore N95 masks everywhere. Attempts at a repeat saw me get a MRSA skin infection a few months after treatment, other neighbors were also having MRSA problems supposedly due to a high rodent (ground squirrels, field mice) population after an especially heavy piñon nut crop that year. Living next to the forest, it's difficult to avoid their droppings, etc. if one likes to hike. So I got the infection but wasn't hospitalized, I still had some functional immunity because the MAB didn't wipe out everything like the older FCR/BR combos did. I would think if you mask and wear clear goggles or at least use moisturizing eye drops, as well as wash hands, etc. the risk will be less than patients with other cancers, who have to use traditional chemotherapy. "Not making antibodies" isn't the same risk group as "not making all the other immune system components" that standard chemo/other agents affect. Your doc probably can comment best where you might fall on the "at risk" spectrum. Other diseases, how you have reacted previously when ill with an infection versus recent infections, etc would contribute to their risk assessment for you, specifically.