Is watch and wait still the best early option

[Superdad3]

I know there are many on the watch and wait which is not easy and sometimes frustrating. With the approval of Ibrutinib and other non chemo break throughs is there any support for starting these earlier versus the watch and wait?

[Cllcanada Top Poster CURE Hero]

The new iwCLL guidelines, due later this year still feel Watch and Wait is the best option...

~chris

[Newdawn Administrator]

It's a hard process Watch & Wait but personally I don't favour early intervention. Evidence suggests it doesn't increase overall survival rates. The other issue living in the UK is Ibrutinib wouldn't be offered as a first line treatment unless there's TP53/17p deletion so if I insisted on 'premature' treatment, there's every chance it would be FCR. Timing is essential but I don't want to precipitate additional issues like clonal evolution, bone marrow damage and possible secondary cancers by pushing treatment too early.

I'd say stand fast and 'enjoy' the period unless there's compelling reasons for treatment or severe constitutional symptoms. Emotionally it's hard and there's a feeling of sitting back and letting the foundations crumble but shoring them up too early isn't the best strategy in CLL. Others may disagree.

I note from your previous posts that you find this approach frustrating Superdad. How are you coping with things presently?

Best wishes,

Newdawn

[Superdad3 in reply to Newdawn]

Reason why inquiring regarding early intervention is I know other deletions and health issues can arise as CLL progresses, possibly other cancers and impact to organs. I am reading alot probaby too to understand all the options

I have good days and bad days more emotional than physical although at times I don't have the same level of energy, might be due to stress, age or CLL, maybe a combination of all three. When I am busy I completely forget about it and its like I am normal. The idle time or when I have to do something related to it I struggle. I went for the Pneumonia shot at my GP based on what I read it needs to be the Prevnar13 for the first shot. They never checked which one they had so I had to re-schedule, kinda set the tone of my day back on thinking too much. There is a point and I am not sure when that I should tell my kids which will be difficult. They are young adults so trying to decide do i wait so they worry less or will they be upset that I waited. Not sure if there is a right or wrong answer for the timing of that discussion.

[Newdawn Administrator in reply to Superdad3]

You were only diagnosed in July Superdad and at that stage I was still a jibbering wreck trying to find solid ground. Give yourself time before you disclose to others, particularly your adult kids. They'll take their cue from you and if they sense your anxiety, they'll absorb the news with more concern. It does ease as we learn and adapt and the important discussions become easier to have. I haven't widely disclosed either and 5 yrs on, I'm relieved about that.

For the first few months I burst into tears even having to mutter the word CLL or cancer. I needed time to come to terms myself first.

Yes you need the Prevenar first followed 2 months later with the Pneumovax vaccine. My surgery gave me the same run around.

It may help you to talk to somebody about this if it continues to cause you anxiety. It's a hard diagnosis by virtue of its uncertainty and it takes our cosy life script and scribbles over it. That's hard for anyone to cope with.

Hope you can find some kind of peace with this soon but don't beat yourself up. It's early days for you yet and we understand completely.

Best wishes,

Newdawn

[baq724 in reply to Superdad3]

I was diagnosed almost a year ago and believe me, it gets better. Luckily I am mutated and have good prognostic markers, but after the initial shock and sorrow, I am back to myself and in the best shape I've been in in 20 years. There are days that go by that I don't think about it until I come here to get my daily dose of catching up with my online friends. I started taking an anti depressant and I've started the taper off phase now.

I've convinced myself that this disease will be conquered in my life time and most likely before I need treatment and if I do need treatment, the standard will have changed. So many treatment updates and improvements have come about in the last 11 months that I can't even count.

Enjoy life and don't waste a day. My energy level improved once I "got my mind right".

You've found a great group of people here that will provide hope and facts to help you along the way. Hopefully in the future this will be a place where we can catch up with old friends and not mention the disease that lies forever dormant in us or that we once had.

[Hidden in reply to Superdad3]

Superdad3, When I was diagnosed the only thing that made me hesitate to tell my adult children was the fact that one of my daughter's was to be married in a few months. But I personally felt it was important not to wait so I told them. i think it was about 2 weeks after being told myself. I was surprised at what a big relief it was for me and wished I had told them even sooner. It was like a huge load was released, and they were glad to be included because we are a family and are there for each other in the good and the bad.

I used to work in bereavement in hospice. I worked with families both before and after the death of their family member. One of the things that I saw that caused the most stress in family members was when they were not told - when the sick family member kept secrets from them or delayed telling them. Put yourself in their shoes and think about what your reaction would be if they waited to tell you they had CLL, or if your parents had CLL and waited to tell you. You cannot protect them from the pain of hearing the news, but you can add to it by not trusting that they can handle it in whatever way they need to do that. When a child knows their parent keeps bad news from them to keep them from worrying, they actually worry more because they never know if and when there is something wrong in the family.

Having said all that, it is absolutely devastating to hear the news ourselves and it certainly takes time to adjust. The way we do this I suppose is different for each of us but ultimately it comes down to facing our own mortality. For me personally, I come from a family with a lot of longevity. Most live into their late 80's and late 90's. I always figured i would die when i was really old and by then I would be ready for it. Even though I still could live that long, I couldn't adjust to the diagnosis without also adjusting to the fact that there is a chance I won't. I personally saw this as a blessing in disguise cause as we all know, anything could happen anytime. I knew what I needed to do, so I did it and now i am relaxed with whatever course my CLL chooses to take. This post will get way too long if i go into what it was I needed to do, but somehow I knew it my heart what it was. And what helps most of all on this journey is having the support of my family, which I wouldn't have had I decided to wait to tell them for fear of worrying them.

I wish you only the very best.

Vivien

[Indolent]

With the high cost of the newer treatments, being in W&W as long as possible makes sense. Why incur the extra cost, if it is not needed? Being in W&W is a drag, but being broke is no fun either. Besides, as time passes, newer treatments are coming online and the competitive landscape is opened to new options. This will hopefully provide some cost relief.

[Tommays56]

Hi Super

In looking at all the possible things that can go wrong with treatment due to the unique variations in each CLL case i am also stressed BUT quite grateful that my condition requires waiting as it is possible i will never need treatment or by the time i due there will be a better option

[Superdad3 in reply to Tommays56]

I hope for the same and there seems to be momentum the last few years for new treatments and combining treatments.

[MelioraDay]

We don't have the data at this point to know if W&W is superior to earlier treatment with the newer agents. It could be that earlier treatment with the non-chemo therapies is superior. We just don't know, but a lot of good researchers are trying to get the answer to that question. As the clinical trial data matures, the iwCLL guidelines for initiating treatment will evolve. When all we had was chemotherapy for CLL it was very clear that it was better to wait as long as possible for treatment. And as long as we don't have the data regarding the newer agents, that treatment approach will continue. Unfortunately, with chronic diseases it takes years to figure out non-inferiority of various treatments with clinical trials.

There are many factors that determine what the treatment window is for each individual with CLL. This is not static and as clinical trial data is evaluated I would think that treatment window would over time move toward earlier treatment to avoid all the problems associated with CLL, especially if the immune system can be restored and not damaged by the treatments. So the jury is still out, and it is up to each of us together with our CLL care team to figure out where our treatment window is. It is just as important to not treat too late as it is to not treat too early.

[AussieNeil Administrator in reply to MelioraDay]

Excellent summary of the current situation, in particular the mention of the present challenges of restoring our immune system after treatment. (Currently ALL CLL treatments are unable to selectively remove just the cancerous CLL cells; they wipe out healthy B-lymphocytes too. So after treatment, we struggle to develop antibodies to new infections - our immune system is permanently impaired.)

I'd also add that treatment accelerates the development of clones with further genetic damage compared to watch and wait. That can lead to an aggressive form of CLL which no longer responds to the treatment drug - we become refractory. Until we can better predict who is likely to develop resistance and we have good availability of alternative drugs to use should that happen, it makes sense to hold off treatment until absolutely necessary.

We are approaching the time when watch and wait will no longer be the default option at diagnosis, probably for a select few initially that have the right CLL prognostic markers, but that option will initially only be available at CLL research institutions.

Neil

[MelioraDay in reply to AussieNeil]

One of the first questions I asked my CLL specialist/researcher is whether he believed my immune system could (not would) be restored if I was treated with one of the targeted therapies. He said “Yes. It is like taking a tarp off the lawn.” He was talking specifically about me and my situation. That was two years ago and I don't know if he has found any reason to change his opinion.

Cirmtuzumab targets an ROR-1 protein which is believed to only be found on cancer cells. There may be other therapies in the pipeline that are highly selective for CLL cells that I know nothing about. I would think there are many. One of the difficulties with CLL is that it is such a heterogeneous disease. It is very difficult to apply data regarding one subtype broadly to all subtypes. In fact we know that we cannot do that. Additionally like fingerprints, no two CLL patients are the same. We do not know if any of the newer therapies will or will not wipe out all B-lymphocytes in any one individual. We do not know whether in some CLL subtypes if waiting is always the best option. We do not know if waiting to treat until the bone marrow is compromised actually causes the bone morrow to lose its ability to restore normal immune function, especially if treated with chemotherapy. We do not know because the studies have not been done and it takes a long time to evaluated outcomes for that kind of clinical research with chronic diseases. So I think we need to be careful about making broad statements about the potential of treatment outcomes, not only because we don't have that data, but because of the highly variable nature of the disease in individuals with CLL.

Case in point is myself, an “n of 1”. I started treatment extremely early by CLL standards on the basis of fatigue. My highest white count was 39, but usually ranged between 25 and 29. I had all the positive markers; 13q deleted, mutated, Zap 70 negative, low B2M, normal immunoglobulins. All other labs totally normal. The only down side was just before starting treatment last December with Venetoclax, we found out from the cytogenetics on my bone marrow that I had 4 abnormalities, giving me by current guidelines a complex karyotype. I had clonal evolution during the 4 years since diagnosis. My specialist commented that in retrospect it was therefore probably better that we began treatment earlier rather than later. Clonal evolution, especially with chemotherapy, is a big concern. The early data suggest that the risk of clonal evolution is less with targeted therapy. What we do not know for any one individual whether the risk of clonal evolution is greater than or less than with treatment vs. clonal evolution that can occur over time without treatment. We just do not have that data or a crystal ball.

After starting treatment my CBC normalized at 4 weeks. In looking back at my CBCs from when I was in my 20's (I am now 64), they look almost identical. My T-cells and immunoglobulins are totally normal and actually improving in the normal range. So I must ask myself if in my case my CLL specialist was correct in saying my immune system could be restored. We do not yet have that answer.

I have worked in healthcare in many capacities since 1971, most recently in medical research (not CLL). I have seen a lot of theories, treatments, opinions, and things we thought were irrefutable “truths” come and go. With the research I have been involved with, the greatest errors occurred when I made assumptions. Many things in medicine are done just because they have always been done that way. When we start to look at why we believe some things or do things a certain way, at times we have found no factual basis for the assumptions and at times have found the reverse to be true. So we always need to be asking questions and not accepting the status quo, at least in our thinking. That's how we push the envelope in research. The earth is not flat, but it was a hard route to proving it was round.

Practically speaking, we have to deal with what we currently have available to us for our situation and our geographic location based on the best thinking we have available to us. The CLL field is moving forward rapidly, so at this point, if we can wait for treatment, that is probably the best option. The more data we have and the better the treatments become, the better our individual outcomes to treatment will be. All therapies have potential toxicities. But I whole heartedly endorse Neil's statement that we are approaching the time when W&W will no longer be the default option at diagnosis, even if only at research institutions.

We need to be very proactive in our CLL journey. Ask the questions, push the envelope, trust your CLL specialist but verify and get second opinions if you are not satisfied. Ultimately all of us, for the most part, only know what we have been told or experienced first-hand. No person or doctor is perfect. I have seen many mistakes and downright false information given to patients by specialists of all kinds. I have made quite a few mistakes myself. There is so much information out there in any field that no one person can know everything. Even the best doctors can make mistakes, and there is so much yet to be learned. The good news is we have every reason to be optimistic about the direction CLL research is moving. I firmly believe this is a disease that will be cured.

[Newdawn Administrator in reply to MelioraDay]

Excellent, informative response MelioraDay!

Food for thought indeed.

Newdawn

[AussieNeil Administrator in reply to MelioraDay]

I agree with Newdawn regarding your response and have corrected my mistake in saying "Currently ALL CLL treatments are unable to selectively remove just the cancerous CLL cells...", to "Currently ALL approved CLL treatments are unable to selectively remove just the cancerous CLL cells".

Good to hear you are doing so well on Ventetoclax with a complex karyotype.

Neil

[Farrpottery in reply to MelioraDay]

Is there an earlier therapy for CLL in the watch and wait period that's recommended prior to chemotherapy?

[AussieNeil Administrator in reply to Farrpottery]

Depending where you live and your CLL markers, you may be eligible for non-chemo treatment, simply because chemo treatment won't work well. There are some older non-chemo treatments, but they aren't very effective and only useful in rare cases...

[MelioraDay in reply to Farrpottery]

Any FDA approved CLL therapy can be used front line for the treatment of CLL when you meet iwCLL guidelines for treatment. However, as AussieNeil explained, chemotherapy won't work well with certain subtypes of CLL, and other therapies such as Idelalisib are not recommended front line in CLL. The treatment decision needs to made in collaboration with a CLL specialist (if possible) and the therapy selected will depend on the genetics of your CLL, your treatment goals, age and co-morbidities, insurance coverage or availability of clinical trials, as well as your specialists treatment philosophy and experience with the various therapies for CLL. I refused chemotherapy and my specialist and I decided to begin treatment front line with Venetoclax. But remember, each of us is unique and this decision needs to be made between you and your CLL specialist.

[Cllcanada Top Poster CURE Hero in reply to MelioraDay]

This may be true in the U.S., certainly not elsewhere... off label use is virtually unknown in CLL in Canada, for example.

Location, location, location

And it may be that your postal code, ie your province of residence, greatly impacts treatment availability and decisions, as does access to private insurance coverage.

~chris

[Bubnojay]

Hi super dad

I feel I can best help by reiterating what Newdawn replied.

These are very early days for you and you have not yet come to terms with your diagnosis. For many of us panic sets in and we expect to be treated straight away which is what happens with solid tumour cancers. We interrogate Dr Google sometimes scaring ourselves, especially as lots of data you will find there has been consigned to history.

We always want to do something to help ourselves, many here were in an awful state at diagnosis not knowing where to turn. These are many who will respond to you, like Newdawn having been there. So, you are not alone.

Unless there are pressing symptoms like bed soaking night sweats, overwhelming tiredness, frequent infections, there is quite a list, then the waiting game is the best for now.

Nearly 7 years into my journey I am still playing the waiting game. Initially you are far better off sticking to communities like ours where there are folk with vast amounts of knowledge, once you get the basics you will be able to go forth and investigate.

I know it is hard at first but this was my strategy in the early days, I wake up, drink my coffee, ask myself how do I feel? I feel ok, so off to the gym or work, consigning thoughts of CLL to the brain bin until tomorrow when I do it all again.

Childish I know but worrying and anticipating only spoils the day, with this disease there is time. You will come to terms with it, for now the future is brighter than it ever has been.

Look after yourself, eat healthily, exercise if you are able to, and finally live for today.

Best wishes always

Bubnjay1

Ps there really are worse things out there.

[Yelverton in reply to Bubnojay]

Interestingly this was one question, I asked my first Haematologist on my second visit, when I took a friend a professional health practitioner and this was a question she had suggested. At that time 2016 I was told no early treatment was not to be considered. However another Haematologist, another country, 2017 I have been told yes earlier intervention is being considered more often. And depending on my next blood test might be considered as a candidate. I feel much more confident with No 2 Haematologist as he gave me a much more thorough exam lymph nodes etc , answered all my questions candidly, - I didn't feel with one with No. 1 Haematologist.

[cll2013 in reply to Yelverton]

#2 doctor seems like the right one to stay with. There in lies the best care - - thorough and answering questions. We all have run into doctors who skate through our appointments, leaving us in the dark.

[Superdad3 in reply to Bubnojay]

I appreciate your's, NewDawn's and everyone else that has replied. The board has been more than helpful, it has become a place I can focus my attention and gain knowledge in addition to sharing and hopefully helping others. I know its a process especially initially which is more mending my thoughts and mindset. I believe I am working through it because I have more better days than bad since being diagnosed.

Thank you everyone for your patience and thoughts!

[Farrpottery in reply to Superdad3]

Dear Superdad,

Think of your CLL diagnosis/watch and wait in this way...

If you saw a big ant bed, would you jump in and kick it all around stirring up the ants?

Put your CLL in that ant bed and don't bother it.

Take time with your family and relish the moments. Make memories with your family and friends that you and they can cherish.

God bless your ant bed not to get kicked for a long time.

Sincerely, Farrpottery

[frenchman]

hi super dad,

several times I told members of this community, that I'm on w & w. now for more than 21 years. no treatment but full off cll. feeling okay.

don't worry to much . do every thing to stay in a good condition. move a lot, take your rest if you feel to it. eat well. stress is doing a lot of bad things.

all the others who replyed have more knowledge of cll than I do, but perhaps I did a little bad of help.

stay ahead!!

[cll2013]

Keep W&W as long as possible. No treatment is free of side effects. Keep all appointments