Personal Update on my CLL (Chronic Lymphocytic Leukemia): The Good News
It's been a while since I posted on my personal medical news.
Today in Columbus, it was all good. CBC was happily and boringly normal. My Hgb still shows that I am no longer anemic. My ALC (lymphocytes) is 1.4 which is actually a bit high for me, but certainly a comforting level.
My ANC (neutrophils) was healthy. My platelets are a bit higher than normal again, but that is to be expected due my splenectomy. The spleen gleans the aging and decrepit platelets, so counts are higher when it's missing. I will take high platelets any day over the terrors of single digit counts when my ITP was raging. By the way, the accepted wisdom is that the high platelets associated with a splenectomy do not increase the risk of a blood clot, but ironically ITP which ravages the platelets does. You can both hemorrhage and thrombose with the same disease. Seems inflammation is the enemy. I refer you to the 19th century wisdom of Virchow's triad, a trusted nugget carried in the brain of all medical students.
More on this particular topic soon with some personal revelations, but that is for another post.
My blood chemistries show my liver and kidneys are happy and healthy. The advantages of a vegan lifestyle.
Dr. Byrd would not agree to skipping my next CT scan in three months. The very few late relapses on ibrutinib that he has seen after 24 months (my two year anniversary of living with the TKI magic of ibrutinib aboard will be at 9:30 AM EST on May 7, 2014) are often subtle and begin in the nodes. With my pesky abdominal nodes, that does seem prudent despite my aversion to more diagnostic "radiation therapy". Getting the scan at the newer CT at OSU's Martha Morehouse may cut the rads by as much 60%.
Most relapses occur between 12 and 24 months, so my period of higher risk is thankfully coming to an end.
Today in Columbus, it was all good. CBC was happily and boringly normal. My Hgb still shows that I am no longer anemic. My ALC (lymphocytes) is 1.4 which is actually a bit high for me, but certainly a comforting level.
My ANC (neutrophils) was healthy. My platelets are a bit higher than normal again, but that is to be expected due my splenectomy. The spleen gleans the aging and decrepit platelets, so counts are higher when it's missing. I will take high platelets any day over the terrors of single digit counts when my ITP was raging. By the way, the accepted wisdom is that the high platelets associated with a splenectomy do not increase the risk of a blood clot, but ironically ITP which ravages the platelets does. You can both hemorrhage and thrombose with the same disease. Seems inflammation is the enemy. I refer you to the 19th century wisdom of Virchow's triad, a trusted nugget carried in the brain of all medical students.
More on this particular topic soon with some personal revelations, but that is for another post.
My blood chemistries show my liver and kidneys are happy and healthy. The advantages of a vegan lifestyle.
Dr. Byrd would not agree to skipping my next CT scan in three months. The very few late relapses on ibrutinib that he has seen after 24 months (my two year anniversary of living with the TKI magic of ibrutinib aboard will be at 9:30 AM EST on May 7, 2014) are often subtle and begin in the nodes. With my pesky abdominal nodes, that does seem prudent despite my aversion to more diagnostic "radiation therapy". Getting the scan at the newer CT at OSU's Martha Morehouse may cut the rads by as much 60%.
Most relapses occur between 12 and 24 months, so my period of higher risk is thankfully coming to an end.
Still my clonal instability and my small subclone of 17p deleted cells keeps me forever on alert.
What we really need is a trial for the many patients such as myself that are doing very well on ibrutinib, but are not in a complete remission (CR). How about adding in a PI3K inhibitor such as idelalisib or one of the newer ones following in its footsteps. Hit the cancer clone on two pathways at once. A pincer move. A classic chemotherapy technique, but instead on chemo, we box off the cancer with focused therapies. Next add a potent third generation monoclonal antibody (mAb) such as obinutuzumab once the rascally clonal B cells have been released from the nodes and marrow out into the open spaces of the blood stream where they are easy picking for the antibody. Finally, we add something to mess with Bcl-2, say ABT-199. All this done in a carefully orchestrated and timed dance to maximize efficacy and dodge tumor lysis (TLS) by adding the ABT-199 as the final coup de grâce to make sure the beast will never rise again, but also when the tumor load is low so the risk of TLS is mitigated.
You can't get to cure without first passing by CR and MRD (minimal residual disease) negative.
For me, this is not a theoretical discussion. This is my blood and marrow and proliferative centers in my node that are at stake.
The same applies to many others that are in similar circumstances with ibrutinib and other TKIs.
It may even make long term financial sense in that it may also be a way to limit the duration of therapy with this initial treatment intensification, but with a predicted end of treatment baked into the plan.
I don't want to wait until it's too late so I am hoping such a trial may come to pass, speedily, in my time.
These and similar concepts are beginning to percolate out there.
What do you think?
I am wondering about bouncing such a plan off the powers that could make it happen. Right now it is a small population that would qualify for such a trial, but our numbers are growing fast.
Please give me your feedback.
"You may say I'm a dreamer, but I am not the only one."
More news, personal and general soon.
I wish a meaningful Passover to all my Jewish friends. May we all leave our personal Pharaohs behind and cross dry shod into the promised land.
Labels: 17p deletion, ABT-199, Bcl-2, CBC, Chronic lymphocytic leukemia, CLL, clonal evolution, CT results, Dr. Byrd, Gazyva, good news, ibrutinib, Idelalisib, Imbruvica, ITP, lab results, lymph nodes, obinutuzumab, OSU
posted by Brian Koffman at
9:49 PM
17 Comments:
This complex scenario will likely never take place because it is too complicated and too expensive for government insurance to pick up.
Remember, there are efforts afoot to limit health care, especially in Medicare. Too bad.
Echos of the British National Health System and 'NICE'.
Yes, yes, yes & yes to each to each of your medical hopes, and a final yes to your hope for a meanful Passover. All so very important. Jan
Brian,
When that combo trial starts enrolling save a space for me right behind you.
We could also start our own, I'll trade you 2 Idelalisibs for 3 Ibrutinibs each day.
As an 42 yo untreated patient with slowly climbing numbers and a subset of 17p, I fully support studying a treatment plan such as your proposal. How can I help you get the attention of the heavy hitters who could set these wheels in motion?
Dr. Koffman
Glad your results are so good. Don't ever stop dreaming! Please keep pushing with all the influence you have because what you are saying makes so much sense.
Rob
The MABs are great at cleaning the cruddy CLL cells once they are cleared from marrow and nodes. Oh to be able to test [i]in combination[/i] the current best available marrow and node "clearing" agents--ibrutinib, idelalisib, and ABT-199-- and follow with a MAB (like obinituzumab) to achieve a low-toxicity, durable MRD negativity! You are not the only dreamer Brian... and its ripe for the taking if we can get the machine to comply.
Spare a thought for the untreated patients who are still desperately waiting to receive treatment with single agent Ibrutinib, Idelalisib, or ABT-199. Their lives tick by day after day with only a glimmer of hope of receiving one of the above treatments, wondering if a clinical trial or treatment will become available in time to save their life or if not they will die. Unable to work or fend for themselves they feel forsaken, help them first.
Before contemplating multiple treatment combinations for the fortunate few, such as yourself, the untreated patients should first receive priority treatment. Let the first be last and the last be first.
I know of at least one patient on "I" at NIH who has achieved a CR .. he went in with TP53 mutation and was untreated. NIH is mono therapy "I". So let me be the one who says "Why do you need to go down this multi-treatment path? If you CLL is under control, why do you need more? Are you a CLL over achiever (lol) .. as I remember, you chose an early transplant as well." Just asking for more clarification of the "why" and also a better definition or in depth look at what should our CLL dream be ..
All the best
Lynn S.
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Agree that ibrutinib and its ilk should be more available as a first line therapy. Clinicaltrials.gov today lists several attractive non-chemo frontline therapies now for all three drugs mentioned plus others. There are plans for more such trials, but for some they can't come fast enough. I like to believe it is not an either/or but both paths could be pursued, especially as my ideal would control costs by being able to get off the med at some time with the help of more drugs. This is what's done in most trials and is the basic principle of chemo-immunotherapy such as FCR or BR. It's important to advocate for one's own needs for sure, but I hope none of us, including myself, do so at the cost of someone else not getting everything that they need for their best care.
I love the plan intuitively, and some of these trials will happen with pairwise therapies as executive discussions about the approach continue. The only ongoing pairwise study I'm aware of is the Gilead trial of GS-1101 with Gilead's SYK inhibitor. What are the early results of this study, and what has been the toxicity profile? To take one of your examples, adding obinutuzumab to ibrutinib essentially puts us back in Phase 1 land because we don't know the toxicity of the combination. It's hard for me to make the blind leap from safety to the unknown and some of our CLL docs strongly discourage it.
I hear your Dr. We all hear you ! Just wish those others ( govt, pharm ,insurance , clinical researchers ) would pick up on what you're laying down !! Over 15K being DX every year and 5 grand of us are passing away. Science and social economics of the situation can't happen fast enough.
I am an untreated watch and wait and I feel we untreated owe a huge debt of gratitude and first in first out priority to those who have been treated. After all they have trialed so many therapies to get us to a point where we can even contemplate a partial or complete remission. Kind of embarrassed by a person who prioritizes those of us with the most time on the clock.... seems backwards to me.
Hi Brian,
Being as I am not medically trained to speculate beyond broad conceptual ideas, I would want to know more about inhibiting multiple signalling pathways at once. One of the known knowns is that unlike a targeted clone a signal pathway has a useful function, even if it is hijacked by the cancer into doing its bidding. I do not know about you but in my ~33 months of Ibru therapy I have had a number of minor side effects which have been transient but in some cases reoccurring. This suggests to me that the nature of signaling function is adaptive through the mechanism of cross-talk or in some cases the redundancy of the signaling requirements for normal cell function. Perhaps this can be managed by selective isoforms e.g. Idelalisib or specific docking sites within a selected TK e.g. Ibru or CC-292 etc.. For my money I would like to hear the researchers debate the three types of combo therapies using Ibru. Ibru with Bcl-2 inhibitor (ABT-199), Ibru with a mAb (Obinutuzumab) and Ibru with alternate TKI (Idel). Debate with speculation on interaction.
My concern, not so much with myself, is how would patients be handled who were doing well by having their CLL held in check but who might take on unexpected toxic synergy from a second agent (unknown unknowns)? Lab-Rats like us get our investigative drug free but if a combo fails the data from the pharma Co. would be corrupted to some extent in re-instituting a combo Lab-Rat back to their original trial protocol.
Given the plethora of new agents we will soon need the guidance of Watson.
Last thought - It took me 31 months on Ibru to get to a CR in blood and nodes so the jury is out on how long it takes for Ibru to work its magic in every patient.
WWW
I am not sure I understand all of what you are saying wayne... but it sounds like the gist is, if a combo trial were started say between Ibrutinib and abt199, and for whatever reason it was a failure, how easy would it be for that patient to crossover back to a single agent protocol... for example, to ibrutinib monotherapy. I don't see why it would be any different than any other crossover in say a placebo vs. drug study. Personally I can't envision a scenario where a combo trial would damage the drug stats/prospects in a monotherapy.
Thinking about it from a drug company perspective, there isn't much incentive to pair a CLL maintenance drug with another to potentially deliver a knock out punch. Instead of charging $100,000/year for one drug, now you have 2 or more drugs trying to earn $100,000/year... so the price pressure is downward. Also, instead of managing the CLL for months or years at $100,000/year, perhaps a combo would just eliminate the CLL altogether at once. The revenue stream from that knockout combo drug scenario is dramatically smaller than in a single agent, maintenance setting.
Thats why we need help from research centers, consortiums, the government, and each other to push for these combo trials. Otherwise, it will take much more time than it needs to at the expense of lives, worry, and illness.
Dr. Koffman, any ideas as to how we (meaning us not just you!) can help get these combo trials moving?
Thats very inspiring..WTF!!
GOD BLESS YOU!!! I hope youre so right..this countries healthcare is a joke, do ppl really have to die for them (.I say them, coz id like to meet them) to take action. It is very hard to comprehend, butit no shock $$1st..personal life distant 2nd..SMH, may god be with us all
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