ASH 2018: ECOG trial shows superiority of Ibrutinib and rituximab over FCR

[bkoffman]

Hi friends,

The early buzz at ASH 2018 was rightly about the ECOG trial that was presented on the last day as a late breaking abstract.

In my interview at the opening of the conference, Dr. Stilgenbauer discusses the practice changing significance of this study that proved that ibrutinib and rituximab was superior to FCR for both overall and progression free survival for frontline patients <70 years old..

For more see: cllsociety.org/2019/01/ash-...

This is real important.

This morning I was on the phone with CLL advocates from several different countries whose work is now to change the circumstances for those who live in the countries they serve and to help deal with the fallout until that happens.

Our work is increasingly to ensure knowledge about and access to the best care.

Stay strong. We are all in this together

Brian

[lankisterguy Volunteer]

Thanks Dr. Brian,

We need the active advocacy and patient education you encourage to help us all live longer fuller lives. thanks

Len

[noeagaman]

I wish that I had known this back in October of last year. I had FCR which turned out to be not so good for me. Oh well, I guess that timing is everything sometimes. Thanks for all you do for all of us CLLers. Keep up the good fight!

Chris

[J_88]

Thanks Brian for the information. I hope this changes frontline treatment in Canada for CLL in younger patients.

[Rt2000]

This doesn’t surprise me. The studies I want to see is whether adding anything to the various new mono therapies really improves results for those doing well on them. I have been on ibrutinib for almost 2 years. My labs are basically normal now and I haven’t had any problems. So I feel I shouldn’t rock the boat at this point. But if there was a proven combo or sequence that could get me off the drugs, I might be willing to try. But to double the cost of treatment with a combo that may or may not be more effective seems like a crap shot right now.

[drstan2015]

I am a participant in this study and began treatment in February of 2015. I started out with a WBC of 132,000 and a very swollen spleen. Today my wbc is 6900 and my absolute lymph count is 1.47. I have tolerated treatment well except for worsening high blood pressure. We recently dropped my daily dose to 2 pills instead of three as I am doing well. Overall it has been a very easy course of treatment for me and would recommend it to other patients. I am 61 yrs old and was diagnosed when I was 53.

[Jm954 Administrator]

Quote: "IR was also superior to FCR for IGHV unmutated patients (HR=0.262; 95% CI 0.137-0.498; p<0.0001) but not IGHV mutated patients (HR=0.435; 95% CI 0.140-0.1350; p=0.07)"

We need to see a multivariate analysis of the data regarding the mutated/unmutated/genetic status of patients. We should be able to say that some patients may do very well on FCR and they may choose it for financial or other reasons. Others not be able to take Ibrutinib if they have pre existing cardiac issues or other contra indications and knowing this information could inform a risk analysis/assessment if they are considering FCR.

Jackie

[bkoffman CLL CURE Hero in reply to Jm954]

Good points. The data showed the FCR and IR as equivalent in mutated patients at this data point, though AEs favored IR. I will present more on this analysis soon.

[alpek]

Brian or others with insight, can you elaborate further based on your discussions on when approximately the changes in protocol/guidelines can be expected to be changed in countries such as Canada/Austria/EU? My understanding is that FCR is still labelled as the Gold Standard for young/fit untreated non 17p CLL patients virtually everywhere except from the states. When would be a reasonable expectation for other countries to change their guidelines based on the ASH studies presented? Thanks for all your work/contributions, greatly appreciated by all.

[J_88 in reply to alpek]

Good question, wish i knew the answer.

[Cllcanada Top Poster CURE Hero in reply to alpek]

I think we may see some changes and recommendations after the iwCLL meeting in September, but its almost impossible to know how long it will be for individual heathcare systems...to change... funding may be the issue. Then if acalabrutinib gets approved it changes the playing field again. Likely only second line use, but who knows...

iwcll2019.org

[bkoffman CLL CURE Hero in reply to alpek]

Payers are often more motivated by cost than by survival data. Could be a long time.

[Jm954 Administrator in reply to alpek]

In the UK Ibrutinib will need to be approved by NICE for general first line use, not just TP53 or p17. The planned technology appraisal of Ibrutinib + Obintuzumab was terminated, not sure why so it will be at least a year to go through the process even if they started it soon. The UKCLL Treatment Guidelines will also need to be written.

Jackie

[Zia2]

So this applies to those of us that are 13q, (CLL progressing) treatment naive, mutation status unknown, at age 58 correct? My local oncologist says FCR but my CLL specialist says not necessarily due to newer treatments.

Thanks for all you do!

[bkoffman CLL CURE Hero in reply to Zia2]

If you are mutated, the results are similar at that early point of analysis but IR had fewer side effects. I would do I myself in heartbeat rather that FCR in all circumstances.

[Lola69]

Merci beaucoup Dr. Koffman!

[Hoffy]

I hope this data reaches the community hemotologists. When I was first diagnosed 3 years ago my first hematologist ( Scripps clinic La Jolla ) said he puts everybody on FCR after six months . He was giving me all the negativea on Imbruvica. Bleeding in the brain he told me is a concern. (That is a very unusual side effect and usually related to people on blood thinners- which I am not ).

Fortunately I became educated and went to UCSD. Cll society and Brian were very helpful. Thank you!

Unfortunately there is a huge conflict of interest since some hematologist make a great deal of money off of FCR versus writing a prescription for Imbruvica. They might do better if they can at least Administrotor Gazyva.

I am now at UCSD and doing well on the captivate trial combing Imbruvica and venetoclax trial. I got to MRD negative and now on Imbruvica or a placebo. Most likely a placebo.

I feel very fortunate.

Be well,

Hoffy

[bkoffman CLL CURE Hero]

Couldn't agree more.

[jijic]

Thanks Brian, this is fantastic. Do you happen to know if Germany is changing course for first-line treatment? My understanding is that, without a trial or private insurance, FCR is still first-line, at least for us mutated folks.

[Cllcanada Top Poster CURE Hero in reply to jijic]

Germany has the most advanced treatment of CLL outside the U.S. and many very excellent clinical trials...

translate.google.com/transl...

~chris 🇨🇦

[jijic in reply to Cllcanada]

Thanks Chris - I'm well aware of the trials (though the CLL-13 trial is very likely to close before I need treatment) but was curious about advancements in approvals, since I figured Dr. Stilgenbauer may have covered it! I don't believe that any of the novel drugs are yet approved for first-line treatment in Germany, advancements aside.

[Kshinester]

13q unmutated would now get funded Ibrutinib in Ontario and it’s a good treatment I gather

[Cllcanada Top Poster CURE Hero in reply to Kshinester]

You are right... Here are the criteria for Ontario... other provinces are different.

DRUG NAME: Ibrutinib

Brand(s): Imbruvica

DOSAGE FORM/ STRENGTH: 140 mg capsule

Initial criteria for Treatment naïve patients with high risk CLL/SLL (First-line therapy):

For patients with previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who present with one of the following cytogenic markers:

♦️chromosome 17p deletion; OR

♦️TP 53 mutation; OR

♦️unmutated immunoglobulin heavy chain variable region (IgHV)

Renewal criteria : Patient has experienced no disease progression while on Imbruvica therapy. Initial and renewal approval period: 1 year.

It is funded through the Exceptional Access Programme... EAP

health.gov.on.ca/en/pro/pro...

~chris 🇨🇦