Morning everyone. Thanks for all the great information and posts. Thought you may be interested in an article published today in the NEJM (New England Journal of Medicine). Basically it say much the same as what many of you are already reporting nothing really new. nejm.org/doi/full/10.1056/N...
Have a Blessed day as we say in South Carolina,
Jack O.
Superb results for higher risk patients;
‘After 12 cycles of combined treatment, 88% of the patients had complete remission or complete remission with incomplete count recovery, and 61% had remission with undetectable minimal residual disease’.
Brilliant stuff! 😊
Newdawn
"Patients received ibrutinib monotherapy (420 mg once daily) for 3 cycles," I can't understand what they mean by a "cycle". Could somebody enlighten me please?
It's always good to reply to your own question! A cycle means a week. The video (need to register) says that.
My husband was on the I/V fixed cohort clinical trial and there were 15 cycles of 28 days each. So he started on ibrutinib for three 28 day cycles (apprx 3 months) and the remaining twelve cycles included both I/V.
Would you be able to tell us how it went? Side effects? How did the blood counts change over the stages of Ibrutinib and Venetoclax?
Overall, it went very well. He experienced some side-effects but was able to manage them.
- Blood in urine (stopped when he discontinued baby aspirin 81 mg upon the approval of his cardiologist. Also was examined by an Oncologist Urologist just to make sure it wasn't something else).
- Diarrhea - managed with Imodium
- Had some minor rash, which didn't itch and went away.
- Some muscle spasms but he had those prior to treatment.
- Some muscle aches/joint pain, which eventually stopped.
- Some bruising, which would go away.
- Neutropenia - about midway through the treatment, he needed to get Neulasta shots, which lasted about 6-8 weeks. He continued with them until he stopped treatment April 30th.
Currently, his WBC, ANC, ALC & PLT are still on the low side but are slowly increasing. We are continuing to monitor these with blood tests.
Unfortunately, the clinical trial sponsor hasn't released the MRD results to the clinical trial doctor so we're trying to get that resolved. Obviously, that is something we would want to know.
It is interesting to note the differing dose regimens between those used in this report and those used in targetedonc.com/conference/... In the latter they used 8 weeks ibrutinib at 420mg/day for 8 weeks. Only then was venetoclax added, ramping up weekly 20, 50, 100, 200, 400 mg/day. Note that the latter report's patients had been treated before (50% with FCR).
There, you even answered your own question too Nigel! 😊
That was the regime I’m presently on incidentally.
Newdawn
Good to hear from you Newdawn. To clarify, are you on the regime described in the new 2019 paper or the 2018 one that I cited?
I’m on the U.K. Flair Trial which is also headed up by Prof. Peter Hillmen who was Head investigator on the Clarity trial.
Newdawn
I, too, am in the UK and aware of the Flair trial. Trouble is you have a 1 in 3 chance of being allocated FCR. I have not started treatment yet.
That’s certainly true Nigel. Trouble is, without it you have a 1 in 1 chance of chemo unless you’re TP53:17p!
Worth the punt.
Newdawn
I haven't had a chromosome analysis yet to see if I have 17p deletion. I have just spoken to a helpful CR-UK nurse. There is such a thing as an Individual Funding Request. Also I could ask my GP to be referred to Peter Hillmen, or I could get a private consultation and pay for the lot if I could afford it. I would much prefer early immunotherapy intervention to late chemo intervention. What do you think?
My then haematologist made me a referral to Prof Hillmen at my request. No need to pay privately and in fact I don’t think it’s any quicker.
I did it at the point treatment was on the horizon. The NHS are not eager to offer FISH testing due to cost but a single TP53 probe is necessary to meet the criteria for Flair.
Prof Hillmen is superb but I’m not sure he could tell me much more than was already known at that stage. However, it’s immensely reassuring to be examined by him and hear his views. He referred me to the Flair Trial in my area.
It can be a long process however and a long wait in clinic so take sandwiches.
Sorry, I don’t know much about your staging etc and am on my phone presently or is this about your mum?
Emerging research suggests immunotherapy is a preferable option however FCR can yield tremendous results for the right candidates. Unfortunately you’re unlikely to discover your IgHV status easily on the NHS. I still am struggling to get mine! It won’t alter suitability for FCR to the NHS despite data suggesting it should.
Newdawn
May I ask how long ago you were referred?
I have just reached stage B. 3 nodes.
It's about me. My mother died of CLL 3 years ago and my father died of NHL 20 years ago.
FCR has short and long term toxicity issues. 25% drop out before completion, I expect you know.
I really don't like waiting in clinics due to danger of infection.
Apologies for not recalling your mum had passed Nigel. I had limited access to previous posts when I replied.
I saw Prof Hillmen in Nov last year but it took an age due to my ex haematologist delaying the referral. I eventually started treatment at the end of Feb. due to recurring infection which further delayed the start.
Yes I’m pretty familiar with issues surrounding all treatments and was delighted to be randomly selected for the I&V arm. However, I’d have embraced FCR confidently had it been the selected arm. I’d had nearly 7 yrs on dx by treatment.
I’m afraid Prof Hillmen’s clinic is massively busy and I waited over 2 hrs to see him. It’s worth the wait and refreshments are provided. You could wear a mask if you feel unhappy about infection risk but in truth most people there have blood cancers too.
Best wishes,
Newdawn
I thought I'd asked this from another computer but it hasn't appeared: could you please tell me what "7yrs on dx" treatment means?
Sorry, it means I’d been on Watch & Wait for 7 years by the time treatment was required. Possibly had CLL at least 2 yrs prior to that.
Newdawn
Newdawn, If you wouldn't mind, could you share your experience of first being on Ibrutinib. Were there side effects? Did Ibrutinib by itself bring down the count?
This update I did early on may help Nigel;
healthunlocked.com/cllsuppo...
Of course the Ibrutinib causes the WBC/ALC to soar initially whilst it’s clearing everything out into the peripheral blood but then it starts to settle. The Venetoclax literally brought down my ALC between every blood test which was remarkable. There were times it dropped 10/15 points overnight. I was at normal levels even before the therapeutic 400 mg dosage was introduced.
I experienced joint problems because I already have arthritis but this is perfectly do’able.
How are you hoping to get Ibrutinib with or without Venetoclax first line Nigel? Outside of a trial you’ll have an uphill battle without a TP35/17p which I hope you don’t have!
Newdawn
"How are you hoping to get Ibrutinib with or without Venetoclax first line Nigel?" I don't know at this stage. I'm going to see the haematolgist (one of several) on 25th June. At this stage I think knowledge is power. Thanks for your history.
You’ll need compelling clinical need as it relates to you to get the funding Nigel but I wish you luck.
Newdawn
I've just had an email from Peter Hillmen confirming that Flair is the only way to get I + V in the UK on NHS. Probably, as you say, compelling clinical need is the key. Or one key.
I'm getting back to this thread and specifically Newdawn. Are you there? I have had a diversion for the last 6 months with a respiratory condition that has put me in hospital twice for 1 or 2 weeks. I just saw my haematologist again after 6 months break and his view is that we should consider starting CLL intervention. I am weak, have lost 3 stone, have bronchiectasis and the haematologist says I am no longer suitable for FCR. I have suggested ibrutinib + venetoclax but despite that seeming the best clinical choice I have no chemo relapse to get it on the nhs. I am waiting for chromosome TP35/17p results. which is the other qualifier.
Have there been any other results of ibrutinib + venetoclax published over the last 6 months that I should perhaps know about?
Fortunately I stumbled across this reply Nigel because you didn’t link me to it. If you put a @then the member’s name you’re wanting to ‘alert’, usually a list of names come up and you click on it. Then they receive an alert that you’ve mentioned them in a post. Just for future reference.
Sorry you’ve been so unwell and are now needing treatment. As I mentioned earlier, I think you’ll have an impossible task trying to obtain I&V first line but hopefully your specialist can put forward a good clinical case to avoid FCR (obviously depends on the TP53 results anyway).
This is the latest results I’m aware of from ASH on Ibrutinib & Venetoclax. It strengthens the argument for its efficacy but sadly availability and resources still dominate in the U.K. and we are bound by NICE approvals.
ash.confex.com/ash/2019/web...
It is for high risk CLL however.
Good luck!
Newdawn
Newdawn thanks. Not sure how much weight a haematologist's clinical argument carries. There is a good clinical justification but, as you say, NICE and NHS value my life less than the cost of i+v. Best not to dwell too much until results of chromosome tests are back.
However it is the addition of v to i that seems to give the treatment a positive end point in the form of undetectable MRD, or at least that is the hope. Therefore mortgaging your house to pay doesn't seem so futile.
I understand your frustrations Nigel. Most of us do especially in countries that still limit treatment to chemo first line in the absence of TP53/17p.
It’s one of the reasons I opted for the Flair trial and was most fortunate to be randomised to I&V. This data is needed to strengthen our collective argument.
However, FCR can be spectacularly successful for suitable candidates and due to the prohibitively expensive cost of I&V, socialised health systems will factor that in. Sadly, individualisation of needs is disregarded in this and it’s clear that you have a strong aversion to chemo. You appear to have a familial history of CLL/NHL and perhaps you have experienced enough personally to influence your views on treatment.
Are you not eligible for the Flair trial now due to your respiratory issues?
Newdawn
I think my haematologist said both Flair and Clarity were now closed. I didn't have somebody with me to assist and my clinical 10 minutes was rather rushed.
My understanding is application to the Flair trial closes on the 1st January, 2020.
There could possibly be an eligibility issue however Nigel with your bronchiectasis because one of the disqualifying issues is;
‘You have serious problems with your heart, breathing or digestive system‘.
Regards,
Newdawn
Yes, he could have said that, but in my haste I took down that both were closed.
Clarity was for refractory/relapsed not first line treatment Nigel;
bloodwise.org.uk/research/c...
Newdawn
ok, thanks. As I said, I will wait for chromosome results and then see the haematologist again, but it would be good to have a fallback plan.
This has just been posted in case you haven’t seen it. It may not change what’s on offer to you but the results strengthen your/our case!
ash.confex.com/ash/2019/web...
Newdawn
I had not read this " The combination of Ibr + Ven may have synergistic anti-tumor activity given the capacity of Ibr to mobilize CLL cells from protected niches within lymphoid tissue to the blood where they may have greater dependence on BCL2 for survival." before. Thanks
You may also find the information in this post extremely useful if you haven’t already seen it;
healthunlocked.com/cllsuppo...
Newdawn
Yes, that is a good summary, mostly of the two main monoclonal antibodies with other agents. I am a little wary of those since reading they have a similar 5 year hit on the immune system to getting measles:
newscientist.com/article/22...
“It could take five years for their immune systems to recover, as this is how long it takes in people given the powerful immunosuppressive drug rituximab, which depletes the same cells and is used to treat some kinds of cancer.”
Newdawn My brain is definitely below par. I don't remember writing much of the above or reading the papers. I am just re-reading nejm.org/doi/full/10.1056/N...
I went for a respiratory consultation yesterday as follow-up for bronchiectasis and Pseudomonas A. I am still a respiratory cripple. The consultant's conclusion was that the bronchiectasis is consequent to the CLL and the PA is consequent to the bronchiectasis. So it is really time to address the CLL. I was able to ask the resp consultant about the CT scan of chest and abdomen taken a few weeks ago and there are apparently signs of advancing CLL in terms of lymph nodes and spleen.
There are two issues with getting treatment for CLL, first is the delay in getting seen and second is the chemo vs immuno therapy debate.
The resp consultant said that I should be seeking a second opinion. This is because the correspondence from the haematologist suggests they are ignoring my requests for immunotherapy. But how does one get a second opinion?
Thanks for sharing , excellent article and reference for CLLers
For treatment naive.
Yes untreated J. However, patients who at one time would have anticipated a much more uncertain future! Gives tremendous hope that wasn’t even there when I was dx 7 yrs ago 😊
Regards,
Newdawn
I was just pointing out who those results pertained too. RR has excellent but not nearly as good responses.
I sent the article to my Hematologist this morning and he has already responded to me. I have only been on Ibrutinib for one month and as he predicted my WBC increased from 122 to 156. This is very common when on initial treatment. He is slowly weaning me off prednisone also. Started at 80 mg and now down to 25 mg. reducing 5 mg per week. Here is his response.
"Good morning, Mr. Oxxxxxx.
Venetoclax is a very active drug. The issue will be whether we will add it upfront or reserve it for second line use. We will need to significantly reduce your white blood cell count with ibrutinib before we can add venetoclax if we use it upfront. Best regards, Dr. Nxxxxx"
Your specialist obviously knows your clinical situation best. Good that he’d responded so promptly, it’s not a service I could rely on.
I am on Venetoclax after 2 months on Ibrutinib (clinical trial in U.K.) and my WBC was higher than yours when I started on Venetoclax. That’s why it’s gradually introduced on a phased ramp up to avoid tumour lysis syndrome. It’s a powerful drug that needs careful monitoring.
However, your situation could very well be resolved on Ibrutinib and it’s good to know Venetoclax is there for second line use for you.
Newdawn
There's an Editorial in the same issue of NJEM that highlights the IMPLICATIONS of the I&V combo in terms which are easy to understand. Read it (first, I suggest) in combination with the article cited by jdolinger and the picture becomes even clearer.
See: nejm.org/doi/full/10.1056/N... (can be accessed with the same log-in credentials used for the above cited original research article).
Caven
Ibrutinib +venetoclax
Adding Venetoclax to Ibrutinib 
Remission with Ibrutinib and Venetoclax
