Ibrutinib related issues

[walkingspirit33]

I am wondering if anyone here has info concerning what is next line of treatment if Ibrutinib dos no longer work or as my body seems to be developing infections related to Ibrutnib treatment .Any info is appreciated.Thank you.

Robert

[Cllcanada Top Poster CURE Hero]

I failed Imbruvica (ibrutinib) due to adverse events after 3 months, but coasted for a year and then started on the just then funded Zydelig (idelalisib) and rituxan, as per the Furman/Sharman protocol...

I year next month and my counts are in range and as my chart says..unremarkable... 👍🏼

Zydelig (idelalisib) has black boxed events, but carefully monitored, by a doctor with experience it should be no problem. The only real minor issue has been colitis, but then, I only have 2/3 of a colon, so it was expected...

The other option is venetoclax, again managed by a knowledgeable doctor.

~chris

[gp7591 in reply to Cllcanada]

Chris- Thanks very much for your note. I'm curious- what did your doctor say about the effectiveness of treatment with the "combo" Idelalisib/Rituxan versus Ibrutinib? Do many people achieve MRD negative- even complete remission (CR)? I assume you're mutated? Perhaps not- maybe the Idelalisib/Rituxan combo is effective on both mutated and unmutated (I don't know). As "combo" therapy now seems to be the focus of many researcher- with outstanding results (e.g.- Ibrutinib with Venetoclax, etc), your comments would be helpful and much appreciated. Many thanks! -G

[Cllcanada Top Poster CURE Hero in reply to gp7591]

I failed Imbruvica (ibrutinib) because I'm an Imbruvica (ibrutinib) bleeder, coupled with increased A.fib... only on it 3 months.

Can't compare Zydelig (idelalisib) and rituxan to it, however I have a clinical CR on I/R after 11 months. MDRs are not very common on either Imbruvica (ibrutinib) ot Zydelig (idelalisib) and often take a couple of years to achieve... if at all.

I'm FISH normal, mutated, but also a Richter's survivor so who knows what genetics are driving the disease.

Certainly combo therapies hopefully cycled, will be the treatment path in the next 5 years or so... what combination proves most effect remains to be seen...

~chris

[gp7591 in reply to Cllcanada]

Chris- Many thanks! I'm so glad you're doing exceptionally weill on Idelalisib and Rituxan. Just curious- since you're done a lot of research on the topic- have any well known CLL specialists "ranked" the best "combo" therapies? I understand each "combo" is different because all patients are different, but it would be interesting to see some comments comparing roughly equivalent patient populations and different "combos" (i.e.- Idelalisib and Rituxan, Ibrutinib and Venetoclax, etc.). Any thoughts?

[Cllcanada Top Poster CURE Hero in reply to gp7591]

Too early to rank anything, just no data...these things take years to evolve and develop a concensus...

[Fant1924 in reply to Cllcanada]

When we are within normals for our blood, it is indeed “remarkable!”

[Spacee]

I just saw a video from Dr. W at MD Anderson (sorry I don’t know how to spell his name. Maybe Weirda?) He said they are using Venetoclax now after the I drug doesn’t work. I am keeping an eye on these two since I feel they would be the option for my mutated husband. (I can’t spell but now I can pronounce Venetoclax!

Spacee (Linda)

[lankisterguy Volunteer]

Hi walkingspirit33 & Spacee,

Chris responded above about his success on Idelalisib.

I had great results for 30 months on Idelalisib, and 9 months of problems on Ibrutinib.

So in June 2016 I started Venetoclax, and within 9 months I was MRD neg in blood and marrow. In Sept 2017 I stopped all treatment at the recommendation of Dr. Furman with the hope for several years of remission, and will restart Venetoclax when needed.

There are several of us here on CLLSA and the CLLForum that have taken Venetoclax either after Ibrutinib or along with Ibrutinib and reached MRD neg and stopped treatment.

Most CLL expert doctors should be aware of the recent results, and will have more clinical result data from the 2017 ASH conference in a few weeks.

Len

[PlanetaryKim in reply to lankisterguy]

Congrats Len on achieving MRD neg and coming off treatment!

kim

[gp7591 in reply to lankisterguy]

Len, Thanks so much for your comments. Not sure- but maybe we chatted in another CLL Forum? I'm so glad Venetoclax has worked well for you!! What does Furman say about the latest Ibrutinib/Venetoclax combo therapy? I saw results from another study that said 80%- 100% of patients had a positive response, with even roughly 70% of 17p patients achieving MRD negative status- a remarkable result and a good sign for the use of "combo" therapies. Any thoughts? Whatever you can share will be very much appreciated. Wishing you good health and success in the years ahead! -G

[Cllcanada Top Poster CURE Hero in reply to gp7591]

iFCR is looking very good as well 83% MRD... highest of any treatment yet... as per Dr. Davids video...

healthunlocked.com/cllsuppo...

~chris

[gp7591 in reply to Cllcanada]

Chris- Does that study include unmutated patients? Any 17p?

[Cllcanada Top Poster CURE Hero in reply to gp7591]

Yes ..view the video.. it is clearly stated it does... high risk, low risk, mutated and unmutated.

Tiny numbers however.. only 35 patients... but encouraging

[gp7591 in reply to Cllcanada]

Chris- Many thanks! Yes- that is very encouraging. However, for those like me who would really like to avoid chemo unless it is absolutely the last option, I'm wondering if there might be some "triple combo" therapies being considered, like Ibrutinib, Rituximab and Venetoclax, to specifically avoid chemo but utilize the "best of the best"? I haven't seen anything on this yet, but perhaps you have. -G

[Cllcanada Top Poster CURE Hero in reply to gp7591]

There are as many combinations and purmutations as there are drugs...

Don't get stuck on these first generation small molecules, there are clearly better second and third generation options in the pipeline...

The best of the best depends on what is available at any given time and your situation.

No cookie cutters in CLL

[gp7591 in reply to Cllcanada]

Cllcanada- Many thanks! I'm wondering when acalabrutinib will be approved- and when Venetoclax will be broadly approved for all first line patients. I've read "rumblings" that acala could be approved very soon...

[jaysearch in reply to lankisterguy]

Where do I find this Dr Furman?

[lankisterguy Volunteer in reply to jaysearch]

Dr. Richard Furman MD

Weill Cornell Medical College @

New York Presbyterian Hospital

Hematology & Oncology Department

520 East 70th St. Starr/Payson Building 3rd Flr.

New York, NY 10021

Patricia Feeney,

Senior Medical Secretary, direct: 646 962 2075

[e-mail]

Main line: 646-962-2064

Fax: [phone]

[jaysearch in reply to lankisterguy]

Thank you. I live on Long Island, and will try to contact him later in the spring.

[Lola69 in reply to lankisterguy]

Are u stating that one should stop taking pills? My doc said never to stop taking my imbruvica ..

[lankisterguy Volunteer in reply to Lola69]

Stopping treatment of Venetoclax or Ibrutinib and Venetoclax after reaching MRD neg in bone marrow is a hypothesis that several top CLL docs & clinical trials are testing currently. OSU and the CLL Forum have several patients testing this theory currently. Too early for any statistics or proof.

youtube.com/watch?v=I-B8iEi...(Not working as expected?)

Dr. Furman convinced me to try stopping Venetoclax, but after 4 months pause my CLL cells went from less than 0.01% to 1.00% so I restarted Venetoclax in Jan 2018.

He indicated that several other patients, a few on Ibrutinib for >5 years and more on Venetoclax for 1 to 1.5 years, were successful with the strategy and have remained MRD neg for over 1 year.

So there are no absolutes, just theories. Only time and lots of data from rigorous clinical trials will determine which strategy results in the longest OS = Overall Survival.

Len

[lankisterguy Volunteer]

Preliminary / early data indicates that a higher % get to MRD neg on a combination of Ibrutinib and Venetoclax vs. Ventoclax alone. But Dr. Furman admits it is a hypothesis & as Chris says above: Too early to rank anything, just no data...these things take years to evolve and develop a consensus...

Len

[Dyoung4now]

Does anyone know if the Ibrutinib/venetoclax combination reduces or eliminates the Ibrutinib side effect of atrial fib?