Obinutuzumab

[Guinness4822]

Just wondered of anyone has had obinituzumab iv with venetoclax as this is a treatment option I have been offered.

[lankisterguy Volunteer]

Hi Guinness4822,

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That combination obinutuzumab / Gazyva & venetoclax / Venclexta often called V+O or V+G or the reverse order O&V or O+G is one of the most often used limited duration therapies use in the USA and many other countries. The UK NHS had settled on V + R (rituximab / Rituxan) probably following an earlier study and approval. But I believe some later studies showed statistically better outcomes (longer remissions) using obin / Gaz for 12 months as first treatment or 24 months with previously treated CLL.

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You can read several past postings by looking for the box on this page labeled: Related Posts

*Obinutuzumab (gazyva)

*Obinutuzumab + venetoclax

*Obinutuzumab and Venetoclax

*Obinutuzumab and Venetoclax

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Len

[Skyshark in reply to lankisterguy]

V+O 12 cycles is first line short duration in UK NHS since late 2021. Being supplanted by short duration I+V 15 cycles since May 2023.

Long duration Ibrutinib or Acalabrutinib are also 1st line. Zanubrutinib may still get get approved Nov 2023 if NICE reverse their non approval decision. I've done my bit. They clearly wanna as the draft said it "would be welcome". They can change this draft but the next draft that will appear sometime October will be final except for correction of factual errors.

Although it will be much more costly and reintroduces 9 IVs for O, A+V+O is in NICE guidance development list. Should be up for approval end of 2024 or early 2025. It's overall 96% PFS at 48 months suggests the median will be something incredible, everything else will be 2nd place. (simple linear projection is 50 years!) Seems to be just as good as a 2nd line.

VenR 24 cycles is 2nd line for R/R in UK.

[Skyshark]

See my replies on these posts.

Simpler.

healthunlocked.com/cllsuppo...

Long with numbers that are now incorrect.

healthunlocked.com/cllsuppo...

[Gradyboy]

This is a very common treatment as others have said. I am currently in cycle 8 almost cycle 9. I would be happy to answer any questions you have, if I can. This is my first treatment so I am learning as I go. I'm in the US. I can tell you it has been a painless process so far for me with excellant results. Ask away if you have questions.

[Guinness4822 in reply to Gradyboy]

Thanks for reply guess main concerns are side effects, which seem similar for any treatments offered.

[Gradyboy in reply to Guinness4822]

I have been lucky. I don't have any side effects. After the O infusions I would be a little hyper for a day or so but felt good. The Venclexta I take right after dinner and honestly can't tell I've taken anything. Zero side effects from the pills. I'm 61 with no other health conditions. My main cll symptom was massive lymph nodes external and internal. They disappeared quickly after starting treatment. I highly recommend taking the Venclexta after dinner. I was told that by many people when I started. I had a PET scan 3 weeks ago today to check for cll in my lymph nodes and it came back saying complete resolve. I couldn't be more thankful for this treatment regimen. Some vitamins have bothered me more than this has. I am getting close to a year with only a couple months left fingers crossed and many prayers being said that it continues on. Best of luck to you. Keep a good attitude most people seem to do very well on O&V. You may be very surprised how much better you feel. -Robyn

[Guinness4822 in reply to Gradyboy]

Thanks Robyn a very helpful post. 👍

[Guinness4822 in reply to Gradyboy]

Hi Gradyboy,My best friend is also a Grady from Keery originally now in Leicester but his son recently married a Chicago girl and he now lives there with their 3 month old baby. Hope your doing well on medication, 6 weeks in for me and no side effects. Thank God.

[Gradyboy in reply to Guinness4822]

Grady was actually my dog's name. Mine is Robyn. 🤣 I am doing very well. I will be done soon. Not exactly sure of date. I have an appointment 11/7/23 and will find out then.

[Guinness4822 in reply to Gradyboy]

Ok 👍 good luck Robyn.

[Gradyboy in reply to Guinness4822]

Same to you!

[Rico49 in reply to Guinness4822]

everyone is different. I've had six cycles of O and been on venetoclax for 3.5 weeks with no side effects. excellent results so far.

[GrumpyFrog]

I did a course of O+V a couple of years ago. I seem to be in complete remission now with no detectable CLL. This is widely regarded now as one of the most effective and "easiest" treatments available. While there are some side effects, these appear to be much better than some other treatment regimens. See my previous posts.

[Fleur1-]

Hi Guinness,

I embarked on this treatment with much trepidation after reading many different experiences of its impact, I would say go with a very open mind as people react differently depending on their personal circumstances and status of disease, I personally have had no side effects or negative impacts so far which I’m delighted to report, I commenced this in the U.K. this June and I’m up to maximum of my 12 month plan. I was asymptomatic and only had to start treatment due to lymphoma tissues in my throat that started to impact my airway, this has completely gone already and life is pretty much BAU status for me, I wish you well with your treatment, good luck x

[mush56]

No I’m on ventoclax & retuximab no offer of O& V hope all goes well for you

[stevesmith1964]

HiObinutuzumab is fantastic along with Ibrutinib it took me from stage 4 100 % infiltration to uMRD in 240 days. No side effects, been in remission 2 yrs on Acalabeutinib twice daily. Monthly bloods reasonable stable... go for it.

[Skyshark in reply to stevesmith1964]

Ibrutinib with Obinutuzumab is not available to UK NHS patients. "Janssen did not provide an evidence submission"

nice.org.uk/guidance/ta702

For UK NHS, Acalabrutinib is a continuous monotherapy. Ibrutinib is either continuous monotherapy or a short duration treatment with Venetoclax.

[stevesmith1964 in reply to Skyshark]

I didn't know that. My treatment was provided under my private health insurance. Shame its not available under the NHS as I know of several high patients in the uk in their 50s who the regime has worked brilliantly.

[Smakwater]

I received O+V in a clinical trial in 2018.

Overall very tolerable and documented efficacy. Durability is still in the observation stage.

Do you have a specific question(s)

JM

[Gradyboy in reply to Smakwater]

Are you still umrd since being treated in 2018?

[Smakwater in reply to Gradyboy]

I have an appointment set up to have labs run on Oct 1st. I do not know if I am still Umrd because monitoring has been with CBC labs from peripheral blood draws. All of my CBC counts are good.

[Gradyboy in reply to Smakwater]

Best of luck at your appointment. If CBC is all good I think that would be a great sign.

[Smakwater in reply to Gradyboy]

Yes, I have ben pleased with the lab results. My neutrophils even returned to normal. The only low numbers are in my IgM.

I would like to produce a durable remission for myself and also to offer hope to those having the unmated risk factor who are considering O+V.

Thanks for wishing me luck!

[Gisygirl]

I had 2 rounds O before starting Venclexta but it made all my white cells disappear and i was in the hospital with septic shock. So have been just on Venclexta doing well.

[skipro]

I have

So far it is working very well

It's the only combo I know about that can provide lasting progression free survival for many years off meds

[Skyshark]

CLL14 Ven-Obi 72 months v's CAPITVATE Ven-Ibr 36 months

IGVHmu/TP53wild, IGVHunm/TP53wild, IGVHmu/TP53del, IGVHunm/TP53del

Ven-O PFS 72% , med 70 months , (PFS 74%) [1] , med 47 months

Ven-Ibr PFS 80% , PFS 81% , PFS 75 , med ~ 36 months [2]

Ven-O at 36 months had quite similar numbers to Ven-Ibr

The short duration of the CAPTIVATE study data is unfortunate. 63% of the people on the study a censored between month 30 and 42. They are down to less than 40 still on the study. Two thirds(66%) of the remaining are IGVHunm/TP53wild, started at 50% (even though classed along with TP53del as high risk). The TP53del groups are down to 2 between them. CLL14 has also seen a large number of people leave the trial after 72 months, there were 3 left at 84 months, started with 76 at 72 months. The Initial cohort was about 200 for both trials.

A+O and A+V+O are also in trials but I'm not yet up to speed with those.

[1] Only 5 subjects with this genetic pair in Ven-Obi arm of CLL14, 80% left study so confidence is very poor being based on one observation of progression. CAPTIVATE had a more useful 12 with these markers and Ven-Obi would most likely show a faster downward trend with more subjects.

[2] At 36 months there were 7 or 8 still on study from 16 or 17 starting. Some left study without an event, which may improve the median. CLL14 Ven-Obi had a similar 16 initially with IGVHunm/TP53del.

[bertie260 in reply to Skyshark]

Skyshack: I start treatment in a week or two. My onc/hem has offered two options - O&V limited duration or A&V limited duration. I am IGHV mutated with no TP53 or 17P del. I am 6.5% pos for 13Q. BUT, platelets are aroud 70, ANC is .67, and Hgb is 8.8. I know O&V is a often a good choice but I am concerned about longlasting immunity effects BUT I will go that route if it may yield the best PFS. A&V may be a slower more gentle approach but may not yield as durable response. So, based of the studies you cited above which of the 2 treatment may be better for me taking into account all my current numbers? Just looking for your opinion not to be taken as medical advise. Thank you.

[bertie260 in reply to Skyshark]

Skyshack: I forgot to mention BMB shows just over 90& infiltration. Sorry. Thanks again.

[Skyshark in reply to bertie260]

A+V is a bit of an unknown but unlike mAb and BTKi drugs there is no reason to suspect there may be an interaction as BTKi drugs block receptors on the cell wall while BCL-2i attaches to mitochondria inside the cell.

mCLL + TP53 wildtype is considered the easiest to treat with best and longest remissions on short/fixed duration treatment. This group responds very well with CAPTIVATE FD V+I having 94% PFS at 36 months from end of treatment. Two out of three in this group that progressed were complex karyotype (5+ markers), all are in PR on Ibrutinib monotherapy. CLL14 V+O for this group achieved PFS 84% at 36 months and PFS 72% at 60 months from end of treatment. Even removing the patients that progressed during treatment or failed to complete treatment V+O doesn't match V+I.

For all other combinations of IgHV and TP53 aberrations the converse is true.

[bertie260 in reply to Skyshark]

Thank you - My thoughts are that if V&I is superior to V&O then perhaps a 2nd gen BTKi like Acala, Zanu or Pirto may yield similar results - all three being in the same BTKi family. I guess the MAJIC trial results - not yet in - may shed some light on this. I would love to know the PFS stats for V&I at 60 or 72 months.