My father's cytogenetics test shows he's trisomy 12.
Zap 70 negative
CD 38 positive 45%
The oncologist has suggested BR. My father is physically fit 57 years old. Apart from mild fatigue and lymphodentpathy he's fine. I've read on this forum FCR give longer remission. But there's a greater risk of infection.
It would be really helpful if people would give their insight.
Has he had TP53 gene mutations done?
Does the report state he is negative for 17p deletion?
How about IGHV mutations?
One thing we always say on here is it’s a good idea to get a second opinion with a CLL specialist (someone who runs clinical al trials in CLL) and explore firstly whether it really is time to treat (the generalists sometimes want to treat sooner than the specialists) and also what options are available.
BR would not typically be offered to a young person as I understand it since if you are going down the chemo route you probably want to get aggressive to aim for a really long remission. At least that’s what our Uk CLL experts talk about.
Of course depending on where you are in the world you may also have the chance of selective non chemo treatments which tend to be well tolerated. The main two are ibrutinib and Venetoclax both of which are licensed first line in the USA.
Given the current state of knowledge where we know that there are lots of treatments that work really well be we don’t know how best to sequence or combine them for a truly long term benefit, UK CLL experts advise their patienrs wherever possible to be treated in a clinical trial context. I’d definitely suggest at least exploring the possibility of trials.
To find a CLL specialist the CLL society page has a full list. Also they will offer a free web service to USA patients who can’t get funding. cllsociety.org/toolbox/cll-...
He is negative for 17p deletion.
We live in Pakistan. I don't think IGHV test is available in Pakistan. Ibrutnib is available but the doc is saving it for 2nd line of treatment because most other drugs available in UK and US
are not easily available.
There was a head to head trial done comparing FCR and BR. FCR was definitely more effective. In the UK we also test for a TP53 mutation. It would be ideal if you could get that done too. But in the uk if someone is not 17p deleted and TP53 is not mutated they would always be treated with FCR first unless there was a clear contradiction to FCR due to other illnesses. IGHV status in the uk doesn’t alter that choice.
The logic from UK experts is that if you use FCR then some patients will get a twenty year or longer remission where they don’t need more treatment.
USA Doctors are often keener to go for Ibrutinib.
But as I understand it CLL experts do not typically recommend BR for young healthy patients whatever their markers are.
Adrian, it would help if you can give the link to the study you are citing.
Adrian,
You’re correct about the recommendations. 5 years ago, I was young and fit. Everyone said FCR was the gold standard.
I opted for a blind clinical trial for BR +\- idelalisib. If I was gonna get chemo, I wanted a new drug too. Instead, I ended up with the placebo.
I’m now headed for treatment again but still feel great. My ALC has been doubling for a while now but the hemoglobin and platelets are fine. 58 months later.
I never needed transfusions, was never neutropenic, or in bad health after my treatment. I was afraid of the toxicities of FCR. You just don’t need to hit it so hard anymore. I now have all the small molecules to consider so BR was very good to me. As CajunJeff said, we’re just stringing the treatments together.
You won’t know which chemo is better because everyone’s experience is different. The science speaks for the group and not the individual.
My motto, be the good outlier on the graph.
Jeff
Adrian when I had Bendumstine I worked every day. RIGHT After infusion and I Did heavy duty Construction. Doctor told me he gave me the the must powerful dose he could. With a neulasta shot the next day. I was very Heathy and young I'm sorry how people perceive Bendumstine. It might just be good for certain patients. ONE day I think they will get it right knowing who is best with there age,health,weight most important there prognostic Markers. WISHING you the very best.
The kind of chemo recommended by a doctor depends on markers. FCR & BR are not usually given for the same markers. And not characterized by strength. It's not like BR is "Tylenol" and FCR is "extra strength Tylenol". FCR is not as you said more aggressive. FCR is recommended mostly for mutated 13q.
Definitely use a CLL expert and second opinions are very important. 💕
BR was indeed compared to FCR head to head. FCR was indeed more effective but BR had fewer adverse events.
I don't agree with that based on my CLL experts explanation. Bendamustine is definitely not considered for 13q mutated. And BR was definitely effective for my 3 close friends who had that treatment.
If the study was just comparing BR and FCR with correct matching markers as to the success rate, then definitely FCR is more favorable cuz mutated 13 q has a more success rate. But my 3 friends having FCR with their markers (different than mine) would definitely not have more success using FCR. 💕
I think BR and FCR are used on just about all sorts of Cll, save for 17p.
The main difference is not in the types of Cll each treatment treats, but rather the intensity. BR is used more for people over 65 and those under 65 who have other comorbidities that make FCR too tough a treatment.
BR is generally considered less toxic too, so a consideration for those choosing chemo is to balance efficacy with toxicity. Is the extra couple of years remission that FCR buys you worth the added toxicity? Will those who do BR relapse earlier, but have healthier marrow for there next treatment?
I think FCR makes the most sense for young folks with mutated IGHV Cll who have an excellent chance of being cured with FCR, that can make chemo worth the risk. Everyone else should do ibrutinib if available, or some trial with venetoclax and ibrutinib. Those who do not have access to ibrutinib and are unmutated, in my amateur opinion, would do best with BR to be in the best shape to transition to ibrutinib when they relapse.
Five years ago I would have said go fcr, it’s gets longer remissions than br. Now I would say go br, you get a shorter remission but with less risk of toxicity. The end game is not how long our remissions last but rather overall survival, how long we can live cobbling treatments together.
Either way it’s most likely your second line choice would be ibrutinib. Since we are in it for the long haul, I would do the combo now that has the least risk of toxic effects down the road. Do the least harm now while they figure out what is the best way to sequence the new, novel agents.
That would be my vote, but everyone is different and it’s not a one size fits all decision with our treatment options.
Thankyou for your kind reply. We got opinion from 2 other oncologist both suggested BR. Your post was very informative. Thankyou.
Hi Haider:
I thought I'd weigh in on your conundrum as I was in your father's shoes about a year ago. My hemoglobin crashed due to 92% bone marrow infiltration and I needed treatment only 7-months after being diagnosed. In response to my low hemoglobin I had 6-rounds of BR starting in May 2018. I am 56-years old, my disease is unmutaed and it is Trisomy 12. Your father and I have a lot in common. I was treated at a major Boston hospital and the logic for treatment given to me by the oncologist was let's go with BR and "save" Ibrutinib for the next round. I didn't question the advice as I was in shock about having cancer. Do I think this was cutting edge advice in Boston in 2018? No. Did it work? Yes. I had a good response and a complete remission. I am OK for the moment and I have been told I will likely get a 1-3 year remission but like everything else with this disease the results are highly variable from person to person. If I could go back in time I would have pursued a clinical trial at probably OSU with Ibrutinib and Veneteclax but that didn't happen so I have moved forward. From your father's position a clinical trial isn't likely possible so I'd say BR is a reasonable option but I am biased since I had a good response and I am symptom free at the moment.
I feel as good as I have in several years after BR. I regularly walk 5-10 miles a day. In fact I walked my dog yesterday morning for 5-miles and then walked my golf course in the evening carrying my bag. All together I walked 15+ miles for the day. The point is this treatment has the possibility to work. There is hope for your father. True, it won't last forever but you can potentially get a break from treatment as Justasheet1 (Jeff) has over the past 5-years. And during your Dad's time in remission the options for second line treatment will likely evolve and improve.
Finally, I will say even among CLL doctors there are varying opinions on which treatment is best and on this forum various patients/caretakers will passionately give their opinions about which treatment should be selected. However, most of the folks giving the advice never have passed even a basic chemistry class. We all suffer from bias based upon what we read, and perceive form our interactions with our doctors. Truth be told this disease is exceptionally complicated even for the brightest minds. Therefore, you need to ask questions, listen carefully and make treatment selections from what is available at the moment.
I wish you and your Dad all the best.
Mark
Thankyou mark for your valuable advice. I am a medical student so i understand most stuff, but still learning. Hoping for the best. He will be starting his BR treatment after a PET scan. I'll keep posting and keep everyone updated.
Did you mean CT scan? They are typically used at the beginning of treatment but not PET scans. Did you say that you’re seeing a CLL specialist?
I wish him the best of luck and to Mark (HopeMe), I passed chemistry class but just barely. 😃
Jeff
He did have 2 CT scans. The oncologist suggested a PET scan to see lymph nodes uptake. PET is being done to rule out aggressive from of lymphoma. His cervical biposy did say SLL but to be on the safe side he still recommended it.
We live in Pakistan. We don't have CLL specialists unfortunately, but we do have american and British qualified heme/oncologists. Pakistan has shortage of specialized doctors because most specialists leave for better prospects in gulf or European countries.
That makes sense now. Sounds like he’s receiving great care.
Hi Hyder
I am from India. aged 73 yrs ,dx CLL in Feb 2013. No bad markers of CD 38 and ZAP 70 . I am IGHV mutated . When the counts are doubling ,hB and platelets are falling , muliple lymph nodes enlarged , Spleen and lever also enlarged , I was suggested to go for BR. though I had no B symptoms like fever, excessive sweats, fatigue
I am negative for del of 17p ,,del 6q, ,del 13q and del 11q but trisomy 12.
I finished 6 cycles of B R in April 2019, No serious events , I had infusion of Platelets and WBCs after 1st cycle . i did not have major problems in the last 4 cycles.
I had CT PET scan before start and after 4 cycle to see the response to the chemo immuno therapy of B R . Lymph nodes in neck ,stomach shrunk, Lever and spleen are normal now.
Hi Jeff:
That comment wasn't intended for you and really it wasn't intended for anyone in particular. It's just that I am amazed how some folks are passionate that xyz treatment is best, despite the complexity of the disease. Yet it is a hard disease to understand and treat even for the most educated and experienced doctors. For example, even your highly trained specialist at MDA outlines proposed treatment options for you in a list of not one but three or four options.
I greatly appreciate your, Newdawn, Adrian and CajunJeff's perspectives to name a few. In fact, I'd be lost without this source of information.
All the best,
Mark
Mark,
There wasn’t any offense taken. Just the opposite, it made me laugh. I’m glad I can help though I truly am no chemist. Just a retired fireman 🚒
That’s where my sarcastic sense of humor comes from.
Jeff
In the absence of the availability of the IgHV test to establish mutational status, I’d be going with the CD38 positive result of 45% as a surrogate indicator.
‘The connection between CD38 expression and IgVH gene mutational status is not well understood. It appears that patients with less that 30 percent CD38+ B-CLL cells are likely to have mutated IgVH genes while patients with greater than 30 percent+ B-CLL cells are more likely to have unmutated IgVH genes’.
So there’s some indication that your father’s IgHV status is unmutated and it’s probably been taken from the original flow cytometry test. FISH testing doesn’t establish the IgHV hyper mutation status.
In this situation I’d agree with cajunjeff on this and go for the BR treatment but ideally, for an unmutated Trisomy 12, Ibrutinib would be infinitely preferable. He could respond brilliantly to both BR and FCR but it does seem that whilst Tri-12’s do well on chemo, the mutational status matters in terms of durability and length of remission. Everything I’ve read leads me to that conclusion.
It’s impossible to predict anyone’s response however because these things are not written in stone and your father sounds young, fit and well enough to cope with either treatment.
Wishing him well, the decision isn’t an easy one.
Newdawn
I'll take B over B.R or FCR just my own experience. Just from my own experience. Just on my own result I think the facts speak for themselves. But listen to all the experts. Hoping the very best for you.
Do they give just Bendamustine? I’ve never heard of that before. Was the B a typo?
Jeff
Well I guess I'm the first 2008 it was just approved Memorial West Cancer Institute . Dr Lyle Feinstein Pembroke Pines Florida. Sorry Jeff Check your facts a little bit better.
Sorry no B is no typo I may have been one of 1st . And I was treated very early . Stage 2,B - Treanda was considered an orfan drug to the FDA. Doc said it would probably work for 3 years . Well I'm going on 11 and in Great shape. THANK GOD AN ALL THE GOOD PEOPLE WHO ARE HERE.
Congrats and long may your remission last. I simply never heard of it given as a single agent before but you are correct, of course. I just checked your facts.
I too received Treanda but with rituxin. I guess once upon a time they gave fludarabine as a single agent too. I’m glad it worked for you.
I forgot to mention, I had my chemo at Memorial Hollywood and had my port placed at Pembroke.
This discussion has been really helpful to me. I’m another trisomy 12 and 55 yrs old. I used to be pretty fit but that has been diminishing since I was diagnosed last Aug. I’m about to finally get IGHV test done. My specialist says if I’m mutated we’ll do FCR (Ibrutnib is not available to me in British Columbia). If I’m not mutated we’ll do BR.
I’ve been feeling rather anxious about this but reading this chain has reassured me considerably. Thanks to all for sharing.
Haider, perhaps you’ll specialize in CLL!
Thanks again everyone
Heather 🇨🇦
Stay strong Jemorgen. Hope you get the best treatment available. Live fully and stay happy. Stress just messes things up. Everything will turn out fine.
I am more inclined towards oncologic oral and maxillofacial surgery. I always wanted to be a surgeon.
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