Leukemia and Fixed Duration Treatment

[tola2222]

Is there a combination of novel drugs and treatment regime for CLL that will allow me to stop taking drugs altogether?

[Downriver555]

Gazyva iv for six cycles/6mths along with a ramp up dose of veneteclax for 1 yr. approved by the fda May 15 2019. I am on this combo and I have 1 more Gazyva treatment and 6 more months of veneteclax. my numbers are all in normal range and I have had little to no side effects.

[tola2222 in reply to Downriver555]

Thank you. There's hope. I'm on ibrutinib now.

[Kmiller in reply to Downriver555]

This is where I am headed next month. I have been told Gazyva has some harsh side effects with the first treatment. Did you experience this? Also did you start this one first and then add Veneteclax a few months later? Appreciate any help or advice. My immune system is pretty much gone, so did you get respiratory issues or low neutrophils?

Thank you,

Kathy

[Downriver555 in reply to Kmiller]

The first treatments of Gazyva is broken into 2 stages. Day one received 100mg IV to monitor for tumor lysis. The remainder 900mg is given the following day after blood work. Uric acid tests are used to watch for too much build up dead cells. The protocol is 3 Gazyva treatments once a week then introduce veneteclax wk 4 starting with 50mg, working your way up to 400mg over the next 5 wks. Gazyva Iv continues at 1x month for a total of six cycles. Veneteclax is continued for 1yr.

I had no reaction to either the Gazyva or the veneteclax. After the first 100mg Iv the next day labs showed significant reduction in lymphocytes and wbc counts. 5 months later all my labs are normal range. I am 13 q deleted, mutated

Status.

[AussieNeil Partner Administrator]

We don't know just yet, but the signs are promising that Venetoclax in combination with either or both a CD monoclonal antibody (typically Obinutuxumab/Gazyva) and a BTK inhibitor such as Acalabrutinib or Ibrutinib, will get quite a few patients to U-MRD in a reasonable time period, after which they can go off drugs for many years. If their CLL returns, there's the hope that they can again have a repeat of their treatment with equally good effect.

See the recent posts on the summary of current research on this topic here: healthunlocked.com/cllsuppo...

healthunlocked.com/cllsuppo... and the

Neil

[AdrianUK in reply to AussieNeil]

I think what should be looked at is the idea of starting venetoclax on someone who has been on ibrutinib for quite a while and has a good but not full response. Such a patience would not have a large tumor burden by definition but if they stop ibrutinib the CLL grows back. I think of it as putting the growth into reverse. You can well imagine that starting venetoclax in such a patient would be good from a tolerance point of view as there shouldn’t be much tumor lysis risk. And perhaps venetoclax (possibly with a CD20 antibody) could finish the job ibrutinib had started and get someone to MRDU and in some cases even a cure (which of course we’d only know if all drugs were stopped and the person remained well for more than a decade).

I’m not aware of such a study being done. But of course if venetoclax has a license for CLL as it does now in the USA I guess a doctor could decide to switch an ibrutinib patient like this out of a trial (with or without an overlap period). Since the price is similar but there is a real chance of it stopping I could see this being attractive to payers.

I guess some doctors may be realuctant to do this because the ibrutinib is working well, so if it isn’t broken don’t fix it might be the argument. Difficult one to be sure about although I’m sure the real CLL experts will be building up more and more experience to help them know how best to advice their patients as to when to do something like this and when to leave well alone.

Over time it may become more and more common to do this as they get more and more confident.

And the other interesting dilemena will of course be if we can’t get approval or funding to use V and I together which way should we sequence them. Is V the golden bullet to be reserved to when all else has failed or should we see it as an alternative to chemo and hence use it first or second line and reserve ibrutinib for people that we can’t get to MRDU and so stop treatment?

Time experience and those clinical trials still running will make all this clearer.

[Justasheet1 in reply to AdrianUK]

Adrian,

I received just 4 rounds of obinutuzamab before starting the ibrutinib. My doc said he’s going to add Venetoclax in a year. I go to MD Anderson for care. None of this was part of a clinical trial.

The obina was to get the tumor burden down before beginning the ibrutinib and I suppose the same can be said for the ibrutinib a year before the Venetoclax

Jeff

[avzuclav in reply to Justasheet1]

I agree with these ideas and strategy. I look forward to seeing results for adding venetoclax after a year of ibrutinib. I suspect it could be even better than this result:

healthunlocked.com/cllsuppo...

[17Pisme in reply to AdrianUK]

I am the very person you are talking about. 17p/TP-53 and participated in MDA trial beginning in 2013 with Ibrutinib/Retuxin. Other than bloody skin issues (Staph infections, etc.) all went well for 4 1/2 years until Ibrutinib began to lose potentcy. The transfer to Venetoclax a year and a half ago was a rough one due to the fact that the ramp up of V did not match up with where I was leaving off. In other words there wasn't and even transfer from one to the other and in less than a week my WBC went from 5,000 to 50,000! Thanks to additional Rituxin infusions we were able to bring the count down into the the normal range where it has remained for the past year and a half. I would encourage anyone making the same transition to be sure that transfer is even. In retrospect I should have continued on I until V caught up.

I am MRD- and have been since V took over. Next July will mark two years on V and at that time my team at MDA & I will decide on whether to stop V or keep on going. What we all can hope for is that these novel agents help us to keep kicking the can down the road until CAR-T or some other agent comes along with the cure.

[Hidden]

and the answer is-none of the novel drugs have been around long enough to give definitive answers. you can use combos and stop taking them but how long the effects will last is unknown.

[Awksom]

I’m on a trial protocol, posted earlier, of Zanubrutinib, IV Obinutuzumab followed by Venetoclax for up to 12 months with the aim to achieve neg MRD and a long term remission.

[skunkbay53]

My husband is on Calaquance and 4 weeks of Rituxan infusions. Calaquance brought his spleen and lymph nodes back to normal and blood counts coming down. First Rituxan showed major improvement in blood counts.

[Hoffy]

I am on the captivate trial. Imbruvica plus venetoclax combined for 15 months.

Myself and many others have gotten to UMRD and are now on no drugs.

Gazyva plus venetoclax it’s not quite as strong but seems to be working with similar results for some people.

I see the future of CLL treatment being combos like this.

We are very fortunate that we happen to be at a time with such good offerings.

Be well,

Hoffy

[Justasheet1 in reply to Hoffy]

Hoffy,

That trial was for relapsed or tx naive?

Jeff

[Hoffy]

Naive. But there are starting to be small trials for relapsed disease.

UCSD has some relapsed people on a similar trial.

Be well,

Hoffy