Gazyva/Obinutuzumab treatment

[craterlake]

Hi everyone , has anyone reached uMRD by using only Gazyva/Obinutuzumab as a mono treatment ? thanks james

[AussieNeil Partner Administrator]

Given you've asked a very selective question, which relies on there being members reading your post who have been given obinutuzumab off label without chlorambucil* , you might find these study reports will better answer what you really want to know:-

CLL-11 Study Results for CLL (German CLL Study Group)

gazyva-hcp.com/cll/efficacy...

Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions (NEJM)

nejm.org/doi/full/10.1056/N...

* The study that resulted in chlorambucil gaining FDA approval for CLL treatment, rightly came under considerable criticism by CLL researcher specialists. Chlorambucil/Leukeran is a very, very old CLL treatment. It was approved for medical use in the United States in 1957! en.wikipedia.org/wiki/Chlor... You didn't really need to be a particularly effective drug to show an advantage over chlorambucil and obinutuzumab was a second generation anti-CD20 monoclonal antibody that was expected to be better than rituximab! The FDA approval outcome resulted in the craziness of some specialists suggesting that their patients not even take the chlorambucil tablets - the gains probably weren't worth the risk of additional side effects from the chlorambucil, Unfortunately, pharmacies couldn't not provide the tablets if you wanted your treatment paid for by your insurance company! There wasn't any study evidence that obinutuzumab worked well without the chlorambucil, so you needed a specialist who had an accepted reputation with insurance companies, or you'd have to throw away your chlorambucil tablets.

Neil

[craterlake in reply to AussieNeil]

Thanks very much Neil , it was interesting history and to learn that your chances of having side effects are higher with the Gazyva as opposed to the rituximab , but the Gazyva works much better . i wonder why the Gazyva is not recommended as a mono therapy ??? ... james

[Palmetto in reply to craterlake]

Actually my husband originally was given Gazyva with chlorambucil and after only 5 rounds was able to be off treatment for 2 years. No testing was done for MRD but BMB was normocytic. Then after only one round of bendamustine and rituxan he got another year treatment free. By that time ibrutinib was approved but because of his long history of atrial fibrillation we decided to try Gazyva and chlorambucil again. This time 3 rounds crashed his neutrophils and wbc and he went off again. About that time studies came in that the chlorambucil did not add anything favorable over Gazyva alone. The next time he needed treatment O and V was the choice and now he is UMRD since last October with great counts now. Not sure Gazyva alone can get you to undetected but sure reduced treatment time and stopped progression for several years. Hope this gives you a bit of information.

[craterlake in reply to Palmetto]

Hi Palmetto , yes it does . thanks for the details of your husbands treatment history .it is always helpful to learn what others have experienced especially when they are now uMRD .. that is wonderful news and gives the rest of us hope . may he continue to be in remission for a long time . blessings . james

[ornstin in reply to Palmetto]

I have had similar problems. After 3 cycles of V & O my treatment suspended as neutrophils and platelets have crashed.at various times. Dont know if it will restart. However, your post does give me some hope for the future. Thank you! Antony

[Palmetto in reply to AussieNeil]

If I may add Neil I remember someone posting on here that they had been treated off and on for more than 20 years strictly with leukeran alone. While they never reached UMRD it well controlled their disease when Whack-A-Mole treatment was needed. (That is what our CLL specialist at Sylvester called it!) In my husband's case since he never had high white counts to start with I believe it did more harm than good by knocking his white cells down to almost nothing and wiping out his neuts and in his case I believe Gazyva alone would have been better for him but will never really know! I do know that he obviously reacts well to Rituxan or Gazyva whenever he had AIHA which probably added to the stretches of treatment free phases.

[AussieNeil Partner Administrator in reply to Palmetto]

Given the wide spectrum of CLL treatment requirements, with about a third never needing treatment, there are sure to be people with very slow growing CLL, which just needs a "Whack-A-Mole treatment" as you put it, every so often.

[stevesmith1964]

Hi, i was diagnosed stage 4 high risk in Nov 2020 with full marrow infiltration and spleen well past my navel. I was virtually asymptomatic to that point. I went strait to 2 unit tranfusion and 6 cycles of Obin, supported by ibrutnib and was in uMRD in 243 days. On daily acalabrutinib and monthly bloods. All stable now for 16 months. Living a full pre CLL and Pre Covid lifestyle

[Iupiter]

I got to uMRD last year with Ibrutinib/Obinutuzumab/Venetoclax after a 15 month treatment. This was a clinical trial.

[Iupiter]

The trial is A071042.

[Flute117]

I am uMRD going on a year after completing Obinutuzumab (6 cycles) + Venetoclax (13 months). I am not aware of solo Obinutuzumab treatment.

[Rpshe1]

I was in a Gazyva & Bendimustine study in Eugene, OR with Dr Sharman in 2015/16. At the end of study no cll cells were detected in my bone marrow. I have not received any treatments since. I am unmutated Trisomy 12. Fingers crossed I reach year 10 before needing treatment again🤞🏼

[Palmetto in reply to Rpshe1]

Bless you that you did well with Bendamustine - that one treatment in combination with Rituxan while initially plunging his neutrophils and white counts so that he only had one treatment when 5 was recommended - got him ready for heart valve surgery in less than 2 months with perfect counts by that time. I can see where that could have gotten you such a strong remission! Hope it reaches year 20 treatment free!!!

[Rpshe1 in reply to Palmetto]

Thank you, though 20 is a bit of a stretch since Dr Sharman guessed it would give me 5 to 7 years. He kind of winced when I said I was shooting for 10 😂

[SofiaDeo in reply to Rpshe1]

Do you have any other mutations other than what is in your profile? You said you got the diagnosis from a flow, but not specific results. Just curious, if you don't mind sharing here, or updating your profile.

[Rpshe1 in reply to SofiaDeo]

What my profile states is what is basically. My onc at that time wanted to do biopsy after my appendectomy in 2011 but I declined since regardless I would be watch & wait. Six months later the Onc requested a flow to determine type. Still watch & wait. Early 2015 my WBC increased 3x’s. I started requesting 2nd (Stanford), 3rd (NIH), & 4th (Dr Sharman) opinions. They all said treatment was recommended as my RBC & platelets were declining. I ended up going to Oregon (from California) for treatment. He had a study that I qualified for that he felt I would get a good response from. He was right!

[SofiaDeo in reply to Rpshe1]

Flow cytometry will say which specific markers were used in getting the diagnosis. That is the info I am asking about. Sometimes a NOTCH or ZAP-70 is tested for, in addition to the CD markers. Sometimes we have other markers in addition to the classic CLL ones, or are missing a classic CD used in CLL diagnosis. And you have not indicated you had a FISH, which is unusual for the US, IMO.

pubmed.ncbi.nlm.nih.gov/315...

In the example below, each patient has a CLL diagnosis but one has the classic weak CD20 and the other is negative for CD20. And CD20 is generally thought to be "required" for a CLL diagnosis, although it isn't 100% of the time.

flowcytometrynet.com/cll-sll

So some are "always" found, and others are "often" found:

pubmed.ncbi.nlm.nih.gov/290...

[Rpshe1 in reply to SofiaDeo]

NIH tested me for Notch and other markers that would make me a candidate for one of their studies. I did not have the markers required to enter their studies.

[CLLBGone]

Not sure if this helps ...

Started O infusions 10/2019, and complted 9th and final O on 4/2020.

Started V on 12/2019 and cmpltd final V 12/2020.

Thankfully, I tolerated both meds very well, and continue to be uMrd.

[tesoro5858]

Hi craterlake. I had 6 cycles (9 infusions sessions total) of obinutuzumab for autoimmune hemolytic anemia (AIHA). The positive benefit is that my untreated W&W CLL went into partial remission! My MRD result was 0.04% at 3 mos post obin and 0.01% at 9 mos (that is 1 CLL cell in 10,000 by flow cytometry in blood). While not uMRD, I am quite low. I am 13qdel and mutated (CD20 bright) so have favorable markers despite developing the AIHA. This could be a reason why I have such a good response to monotherapy with obin plus plenty of CD20 receptors. I have often wondered, as have others who have commented, about using obin every few years to control CLL for those of us that have a fairly indolent presentation.

[Hiker13]

Diagnosed November 2019, age 80 with 17p deletion, 11q deletion. Trisomy 12. IGHI unmutated. Treated with Obinutuzumab and Venetoclax July 2021 to June 2022. Blood flow cytometry showed no cancer in my blood. All blood tests normal. So blessed to have received this treatment.

[craterlake in reply to Hiker13]

wonderful . Amen !