Personal Update on my CLL: I am doing well with a near normal MR and no evidence of resistance to Ibrutinib at 42 months

I had MR imaging of my abdomen and pelvis earlier this week at St. Jude. The results were compared to my CT scans done on June 30, 2014 at Ohio State, about 16 months ago. 

I am now on my 42nd month on ibrutinib as part of the OSU clinical trial.

The abdomen showed no adenopathy. No abnormal nodes. None. No big nodes! 

WOW!

My pelvis did show one plump node in the left external iliac area (drains the lymph from the left side of GU tract) that was borderline enlarged and probably 2 millimeters bigger than it was before. 

Different techniques, different doctors, different times. I don't think the 2 mm. means anything and either does Dr. Byrd so I refuse to worry.

I switched to the less precise technique of MR to avoid the potential cancer causing risks of ionizing radiation of the many CT scans that are part and parcel of clinical trials.

When relapses happen with ibrutinib, they often start in the nodes. And that clearly is not happening in my case. And that is great news.

The other great news was that my blood tests done at OSU for the two common mutations that can lead to resistance to ibrutinib were negative, namely the downstream gain of function mutation of PLCγ2 or the C481S mutation at the BTK binding sites that prevents ibrutinib from irreversibly (covalently) binding. Either one of these mutations could turn back on the signaling. Blocking BTK signaling is the key to the success of ibrutinib in handling the CLL clone, so if the blockade is broken than will lead to resistance and eventually relapse

It is not a perfect test, but I had neither one at detectable levels.

Tomorrow I go for IVIG for my still dismal levels of immunoglobulins and to keep my auto-immune ITP at bay. I will also have routine labs drawn, but I am not expecting any surprises

A week later I am back at OSU for my 3 month check-up.

Flying to Ohio in the late fall and all winter is not predictable, but what I can predict is good care and what I can anticipate is more good good news as I am heading towards 4 years on ibrutinib.

UPDATE: My CBC at the infusion center Nov. 12, 2015 was basically normal. Hemoglobin was really normal at 14.5 so no anemia, platelets were very slightly above normal at 458,000 due to my splenectomy, ALC was at the low end of normal at 1.0 and that makes me most happy and my ANC was a healthy 8.1.  

All good. YEAH!

Hope to see you at our after ASH educational bash at City of Hope on Dec 12. Click here for the details.

More Good News- Update on My Lab, CT Scans, and General CLL (chronic lymphocytic leukemia) Status

My blog has veered far away from the simple telling of my story to more telling of our stories with much B roll.

I am making plans to maybe bifurcate its content in the future, but for now it will continue its happy and diverse life as a personal health blog, a home for research news and video and audio interviews with leading researchers, and a whole bunch of personal analysis and advocacy on what it all means.

I am back from Ohio State where I am still seeing the research team every 3 months and getting CT scans every six months for my clinical trial on ibrutinib. I have riffed on this being too much radiation before in this prior post that includes links to some of the basic research of radiation exposure and its risks, but Dr. Byrd argues that the few relapses he sees on ibrutinib show up first in the nodes, so he wants to monitor me with the scans.

True enough. When I relapsed post failed hematopoeitic stem cell transplant in 2008, the nodes were my canary in the coal mine showing slight growth months before my lymphocyte counts started to move up and my platelets down.

So twice a year CTs are still the plot line for my clinical trial at OSU.

Since diagnosed in 2005, I have probably had about two dozen CT scans!

Add to that the equivalent of the 20 chest X-rays annually I get from flying over 100,000 miles a year, and my risk of secondary cancer is significant. This link with a NASA produced video tells the air travel part of the story.

If you really want to worry, take a look at this article from Medscape on CT scans in NHL.

But this post is not about the danger of CT scans, but about what my last one showed and happily that was stable disease.

I still have enlarged lymph nodes but they have changed little since October of 2012, or for the last 20 of my total of 25 plus months on ibrutinib. My largest sentinel gut node near my liver was about 10 cm at its peak, 7.3 x 3.3 cm just before starting ibrutinib, 4.4 x 0.7 cm in October, 2012 after about 6 months on the medication, then it shrunk to its shortest 3.9 x 0.7 three months later and when last measured on June 30, 2014 was 4.4 x 0.4 which actually represents its lowest volume. It has been fluctuating and when you account for the difficulty of measuring mobile objects in the mesentery and near the liver, is mostly stable since its dramatic shrinking in the first 6 months of therapy. Its a long hot dog shaped node instead of the more common bean shape. The same early dramatic shrinking in the first six months and slight ups and downs since has been the tale for my other smaller sentinel nodes on the scans.

So I have pretty stable disease.

What does this mean to still have enlarged nodes and a touch of CLL in my blood (see this prior post from last April on my flow cytometry report to understand more about my numbers and disease burden)?

The CLL does not proliferate in our blood, so the disease in our nodes and bone marrow are the source of all our problems and I will ignore the blood for now.

There is good reason to believe that these enlarged nodes are still full of CLL, but that it is not proliferating, thanks to the signal blocking from ibrutinib preventing it from getting the messages from its nurse like cells and others to be fruitful and multiply. So chock full of CLL, but it's dormant.

The other more positive interpretation is that these enlarged nodes are just the scarred down skeletons of the cancerous nodes they once were, and there is no residual disease to be found. Unfortunately, I am skeptical of this more PolyAnna hypothesis, and short of a biopsy which is not going to happen, there is not way to know for sure.

So what to do to avoid waking the Kraken?

Hope my genomic instability as evidenced by my 17p and 11q deletions and my complex karyotype will continue to behave with the ibrutinib aboard and not mutate so that my magical bullet no longer covalently binds BTK and blocks its activity?

Knock down the residual disease by adding a second or even a third agent?

Be reactive or proactive?

That is the question du jour faced by many of us now and more in the future whose CLL is controlled but it is not gone now with the new medications such as ibrutinib and idelalisib.

I have probed this recurring and unanswered question in more detail a prior post, and will soon be updating my thoughts on how to avoid being left stranded on third base and not getting home to a cure.

The rest of my news is also good.

My blood counts are boring and despite dropping my cyclosporin to a token dose of only 25 mgs once a day and stretching my 40 grams of IVIG infusions to every 7-8 weeks, my ITP also remains dormant. I think the possible immune stabilizing activity of ibrutinib and my low disease burden may be the factors  that have given me this long ride with high normal platelet counts. I have not been anemic for many months now and my neutrophils and the rest of the CBC are all copasetic. My blood chemistries are in the normal range and only my very low immunoglobulins, namely IGA, IGM, and IGG give proof to that fact that I still have a B cell leukemia, albeit a very sleepy and well behaved one.

More personal clinical and general CLL news soon, nearly all of it good.

I will be posting some of my interviews from ASCO 2014, plus sharing some exciting advocacy news. Busy times.

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. 

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.

IVIG, Lab, and Health Update

Nothing artsy or cool to write today.

Just the facts.

My change to monthly IVIG is getting to be so routine that I forget to update my status. True I still have  ITP as evidenced by my giant platelets, but it hardly an issue with my count at 380,000. True also that after a splenectomy the number should be and has been even higher, but it tells me that my bone marrow is producing platelets fast enough to keep pace with the quicker destruction. I still need my ciclosporin and IVIG- that's the bad news, but the good news is that it is working great.

My right eardrum was severely retracted but not red or inflamed when my family doctor took a look. My hearing is affected. My Weber localizes to the right. Check it out. Interesting old school tuning fork test.  So nowI am on a pulse of steroids to open it up. It helped, but the rapid taper over 6 days with the Medrol DosePak proved to be too quick for this stubborn problem, so I am staying at 24 mg a day for about 5 days before I start the taper. I am off the Afrin with no rebound, still on Nasonex, never touched the Sudafed, and it was never touched by the 14 days of Augmentin. It is better, but not gone, and I worry it will return when I start my taper. The response to steroid suggests allergies, but nodes and tumors are shrunken by steroids too. If it 's not better soon, I will see an ENT.

The steroids of course shot up my white count, but it was all neutrophils (ANC was 11), so no worries. If fact it is encouraging that my lymphs didn't climb. Another reason to always insist on a differential count when they draw our CBC. My lymphs have shot up dramatically in the past in response to the higher doses on steroids I received for my ITP. Maybe my tumor burden is shrinking.

My few palpable nodes are unchanged. A single "shotty node" in the left supraclavicular area, and the persistent small ones in the axillae.  They are not very impressive, and may be residual scarring, but I wish they were gone. I understand the biggest changes in node size with ibrutinib is in the first month of treatment.

My Hgb dropped a bit back into the 12 gram range, but the long term trend is stable. I wish it was climbing, but it's not.

I was so relaxed about my lab, I forgot to check on my chemistries, only to find out the specimen was hemolyzed so nothing to report.

I am in physical therapy for my muscle pains and arthritis and now have more exercises to do everyday.  The steroids are helping the knee pain, but the muscles in my right thigh still grab me.

All in all, many minor nagging issues, small worries, but no drama. I will take it. Others have been much less fortunate.

A Personal Note: My Good News on Ibrutinib

Let me get personal here.

While I believe with all my soul that we are all in this together and I celebrate every move forward as exemplified by the amazing 100% overall response rate of the first cohort in my clinical trials presented in the interim reports on ibrutinib (PCI-32765) at the annual 2012 ASCO (American Society of Clinical Oncology), let me now share my personal good news.

My "n" is one, not statistically significant, but personally critical.

After only one cycle of four weeks of ibrutinib, my CT scan of my thorax, abdomen and pelvis showed that all my lymph nodes had significantly shrunk.

Yahoo.

Some details: Here is what happened to my biggest honkin' mesenteric node left in my belly. It is now measuring 2.5 x 5.8 cm compared to 3.2 x 8.9 cm when I rolled into Ohio to start the trial, a dramatic reduction of about 50% in area and certainly more in volume.

Other nodes have shrunk even more, and they have shrunk everywhere - the pelvis, the gut, near the liver and the blood vessels, and in the axillae (armpits).

Now it is possible that ofatumumab may have played some small role in reducing my tumor burden as my baseline CT scan was done before I started my infusions of that antibody, but if I make the logical but unproven assumption that what was happening to my palpable nodes was being mimicked by what was happening inside, then ibrutinib did the lion's share of the clearing out the cancer. My neck and axillary nodes changed little on the OFA.

But add the ibrutinib, and one formerly huge internal nodes that was 10.1 cm is now a petite 3.3 cm.

And all this in only four weeks, with almost no side effects and nearly normal labs and improved energy.

I harbor no illusions. A persistent 5.8 cm lymph node is still a nasty thing, but I also have no reason to doubt that it and its buddies will soon to be shadows of their former bulky selves. My palpable nodes are certainly continuing to get smaller and smaller.

What I know now for sure is that I have had a profound and deep response, despite my two evil complex clones, despite my failed transplant, despite my new small batch of 17p deleted cancer cells, despite the immaturity of my clone being unmutated and the chattiness of it being CD38 and ZAP 70 positive, and despite just about every bad marker.

This is the best news.

How deep and durable my response will be is my next challenge, but for now there is much to quietly celebrate and good cause to be optimistic.

So I under react, stay both calm and hopeful and move forward.

It has been wonderful to be home for a few weeks with my family and friends and patients and cat and the Pacific Ocean.

This weekend, I am off to Houston to lecture on CLL, transplants and anemia. The weekend after is Dallas, then back to OSU for more lab and to pick up 28 more days of ibrutinib.

Life is sweet.

Dangerously tired but all is well with me and my ibrutinib

Just like you shouldn't text when driving or call your boss when drinking, I shouldn't blog on three hours sleep.

My trip home stated with a 3AM wake up to get to the Cloumbus airport around 4:20AM for my 5:50 AM flight to Chicago as the first leg of my trip home.

Yesterday I got good news. Went for a beautiful walk in Inniswood Garden to celebrate. Pictures to follow.

More good news.

Hgb is back up to a low normal 13.8. No downward trend.

My reticulocytes are just fine at 1.8 (some unproven but possible concerns that BTK inhibition might effect retics which are baby red cells and therefore eventually lead to anemia).

My WBC climbed from 9.8 to 12.1, which was mostly from my ALC going from 2.9 to 4.1. This are very small changes, but could represent more shifting of cancer cells from my nodes to the blood stream. One of the pleasant ironies of ibrutinib treatment is that, at lead in the early phases of treatment, no matter what your lymphocytes do, go, up down or stay stable, it is possible and logical to have a positive interpretation. Nice that is virtually impossible to get any bad news.

Eosinophils are high again following a weekly saw tooth pattern. Absolute count is 1.3 which would normally get my attention.  Seeing it is not trending up, I am not worrying.

Platelets are still super at well over 400,000, partially reflecting the reality that  a spleen less, so they enjoy a longer life span with much less filtering

Neuts are 5. That's nice.

No change in my nodes on exam, but seeing as most are gone or have shrunken in just three weeks of therapy to less than 1x 1 cm, it is hard to detect meaningful change.

I still some gut issues- heartburn, cramps, mild nausea. Nothing dramatic.

Next week, after flying across the country yet again, I get will two CT scans, more extensive lab work, my next 28 days' worth of inbrutinib and the associated diary, and  IV ofatumumab, all on the same day.

From there, the next day I fly to Orlando to lecture before I get to rest at home.

Also, as my follow-up visit is on day 30 and I only get 28 days of pills, I will have been of my magic pills for two full days, something I am not looking forward to.

More on this subject in another post. This may not be an insignificant issue.

I Gotta to Admit It's Getting Smaller

The nodes are continuing to shrink. Smaller today than just a few days ago.

No secrets in the showers. A palpation reality is that soapy hands makes the skin disappears and the nodes easier to find. They are still there, but on they are getting hard to find.

More GI issues with cramps and pain and nausea and diarrhea.

Clinic appointment tomorrow.

Big nodes

My MR showed that my gut nodes that have grown too big, and need attention. Counts are good except for a mild persistent anemia.

Kipps says I shouldn't ignore them or the ones he can palpate, but there is no urgency.

The next step is a bone marrow biopsy and then probably a clinical trial at UCSD. All in the next 60 -90 days or so.

Actually the next step is a nap. I always think clearer after a nap.

And I write better too.

It would be so great to get a long respite from decision overload. My longest rest from having to do something about my CLL was about first 12 months after I was diagnosed, and that hardly counts as I was running around getting contradictory opinions on what to do and not to do.

I could use a break from this chess game.

But that's not to be, and so I will nap and research and meditate and move on.

It is a much better time to be pushed to treatment than say 4 years ago when I went for my transplant. Many more effective low toxicity choices now.

But first, my nap. I love to nap, don't you?

ZZZZZZZ

Lots to write about but I don't feel like writing

Got back from Canada on Sunday after the memorial service for my father. It's been a rough time.

Monday I was at City of Hope and Wednesday I was at the infusion center for my first rituximab (R) in over 6 months.

Despite only using oral Claritin and Tylenol as pre-medications, I had no reaction to a full dose of 500 mg/M2. The infusion was a non-event, even with the IVIG chaser that kept me in the chair for a total of about eight hours

I cheated a bit and briefly upped my cyclosporin (CSP) back from 75 mg twice a day to 150 mg twice a day, as I believe (with no hard proof) that its antileukemic effects are more apparent at the higher dose, especially in combination with R. That's been my story so far. With that increase comes the increased toxicity, so I added a low dose of a long acting form of nifedipine, a calcium channel blocker, favored by transplant docs and nephrologists for blunting the hypertensive and nephrotoxic side effects of CSP. I am now on three drugs to protect my kidneys and control my BP, and before I started CSP I was on none. It ain't chemo, but it ain't benign either.

I will taper back down on the CSP starting tomorrow, but will repeat the same dance again next week and over all six cycles if my BP and renal function behave.

This is, of course complete voodoo, making up my own idiosyncratic treatment protocols, but there is a raw logic to it, so I am taking the slight risk. Plus it fits with what researchers like: Do an intervention and measure the results.

It is also self diagnosis and treatment, which is a fool errand, but I accept the folly and the responsibility of my acting out my plan. Besides, it is a rather trivial move. The big deal is the use of the rituximab for my >6 cm mesenteric nodes, and preventing my ITP from re-flaring, and really no other reason, just keeping the CLL, the tumor load, in check- dare I say maintenance therapy? That is the real blazing of new territory.

So far, only one day post R, many of my nodes are palpably smaller, but none of them are gone. This is the necessary prerequisite but no guarantee for getting the needed response in the pesky gut nodes. That story will need to wait until my follow up MRI two months after my last cycles. Nevertheless, it will be silly not be happily encouraged by my brisk response to such a gentle treatment.

Though "happy" escapes me these days. That will happen, but I will be patient and fake it for awhile.

I can't wait until Friday night services tomorrow to recite Kaddish for my dad. I promised myself to say that ancient prayer every Sabbath for the next year. It is a son's duty, even for a father who shared with me a healthy skepticism for all things religious. It feels right. It feels healthy, and maybe healing.

Lots of healing going on here.

Lots of healing still needed.

MRI tomorrow

What used to take a scalpel, then an x-ray, can now be done with a magnet.

Secret happenings in the deep source of growth of CLL, its proliferative centers, the lymph nodes in my gut and pelvis, not reachable by the longest fingers of the most expert palpating oncologist, will be revealed tomorrow.

Have they grown? How much? What does it all mean?

I am nervous. But I am ready.