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.

So much to share: All of it good.

Fall colors in Columbus, Ohio

Let me explain some of the reasons there are long gaps in my writing.

I am off to Detroit on my own tomorrow to lecture on myelodysplastic syndrome. It will be the 8th different city I have visited in 6 weeks, not including stops at airports and a second trip to Columbus. My agenda still has trips to Columbus x 2, Oakland, Sunnyvale, Chicago, and Atlanta.  Most will be taken as a lone road warrior, all before the end of the year. There is even a small chance of another trip for CME, maybe to NYC in December. Thank goodness that the last lecture on CLL to primary care that I am giving this year is in Anaheim, just a short drive away. January and February look almost as crazy. Medical education work in San Francisco, La Jolla, Springfield, MO, and Washington, DC, and pleasure trips to Ireland and Costa Rica. I am glad to be well enough to do all this traveling.

When I am in town, I am busy seeing patients and doctors and family.

I am left doing much of my reading and writing on planes and in airport these days. Thank goodness for my MACBOOK AIR, though the solid state hard drive is getting pretty full.

Let me bring you up to date by starting with my trip almost two weeks ago to OSU for my ibrutinib trial Clinical Trial NCT01217749.

I could not get out of the CT scans without risking losing my spot in the trial. That made the decision easy.

I refuse the dental x-rays, the body scanners at the airport, and whatever I can, but in one day I have essential five sets of CT scans. It is a small price for access to ibrutinib.

If my biggest complaint is the excessive CT scans and travel needed for the trial, I must be doing rather well.

My news from Ohio and the ibrutinib trial was super.

On the too many CT scans Oct 19,  they found no enlarged cervical nodes. Nothing at all. Nada. Rien du tout.  This is a huge change for the better.

The largest axillary node had shrunk just a little to 2.1 x 1.3 cm and was the only node >1.3 to be found.

The chest remained free of adenopathy as is the usual case in CLL in general and me in particular.

The gut and pelvis is where I had had massive nodes before. The largest node, portal caval, (near the large vein draining the liver, a common site for cancer laden nodes), is still entirely too big at 4.4 x 0.9 cm but it had shrunk from 5.5 x 1.5 cm since June. That is about a 50% drop in area in 90 days. Still a ways to go, but that bad boy had started at 7.3 x 3.3 cm in March. It is less than 20% of the size it was when I started on the trial. One particularly nasty mesenteric node that was over 10 cms six months ago is now only 0.9 x 2.4. No wonder my tummy feels lighter.

And thankful, no surprises. No secondary cancers lurking in the kidneys or liver or lungs. Friends have not been so lucky as I have shared on prior posts with unwelcome findings on the scans.

Well, there is was actually one small surprise, not completely unexpected. My spleen is growing back. This is not of any clinical significant, as my ITP remains well controlled with cyclosporin and IVIG, but will need to be watched. More on that subject later.

Physical exam and blood pressure are all what you want them to be: boring.

Labs are normal except for a mild anemia.

I am hardly cured or even in a complete remission, but every single node has shrunk each time it has been imaged, and by any definition, I am in a deep partial remission.

Ibrutinib seems to be continuing to perform as it best publicity suggests it should for the majority of those in trials. It decreases the tumor burden at a slow and steady by shrinking the nodes where the cancer is most active and productive, and certainly in my case, most prominent. I never had very high lymphocyte counts, but had massive painful nodes. There is every reason to believe, based on those ahead of me in the study, that this painless cancer shrinkage and control should simply continue for who knows how long.

In three short months, my visit to OSU will include more CT scans and a bone marrow biopsy, then the OK to roll over into the continuation trial.

So to celebrate I stopped at the Rock and Roll Hall of Fame on my way home via Cleveland, and spent half my too short visit at the Beatles display. A splendid time was had by all. I highly recommend it.

Rock and Roll Hall of Fame, Cleveland. Ohio

More soon with the truly wonderful news and pictures from my daughter's, Heather, wedding last week in Chicago.

Life is good.

A great middle eastern meal with an important and kindly MDS expert and the amazing Diego Rivera mural and more at the Detroit Institute of Art await this weekend.

But honestly, I would rather be at home reading and writing and walking on the beach and eating organic raw food.

Slight Progression

My MRI today produced fine crisp images that showed my nodes have grown slowly since the last CT in September and now the largest in the mesentery is 6.3 cm in its widest measurement.

What makes it more confusing is that the report from September was revised upward suggesting both that the response to the rituximab after the June CT was very much less than I had thought it was last fall, but on the other hand, the growth since has been quite slow.

But the growth may not have been linear, but rather a U curve with a early drop, and a recent growth spurt in node size.

Remember please that I had more rituximab since the last CT that likely shrunk the nodes (this was never documented and so is just my speculation) that are now rebounding. I will never know for sure, but it makes sense.

More later. Too tired to write tonight.

To CT or not to CT: That is the question.

I saw Dr. Kipps for the first time in 6 months yesterday and the cold facts were good, in fact very good.

My lab remains perfect, and for the first time since transplant, my ALC is WNL. More importantly, my node exam by the meticulous Dr. Kipps and his magic fingers revealed nothing pathological. One small node in the neck was about it and it was around one cm. Nothing else found worthy of comment.

Based on my exam and routine lab, you would hard pressed to say I had CLL or had had a transplant.  Nearly four years out, and I am pretty unscathed to use the language of Dr. Rai.

Moreover the fact that my bone marrow cellularity was normal for my age at 40% told us that my blood making organ had bounced back very nicely from last year's toxic blast. My reserves may be down and may have a more difficult time rebounding from future treatments, but my marrow is doing great now.

In fact, when we look at the NOW, and what else is there to look at, it's all good. 

Sweet!

But Dr. Kipps had a different take on my CT report of my mesenteric lymph nodes doubling in size from 1.1 to 2.2 cm in just three months between the end of December and February.

He was incredulous. 

It doesn't fit with my healthy state and my clean as a whistle BMB.

He is another on a short but prestigious list of docs (Castro, Rai, Forman) to say that CLL doesn't come back in nodes. It likes to stop off in the BM first. Drs. Khouri and Keating might beg to differ. However, Kipps added this important caveat: the only time it relapses in the nodes is post Campath, and that sure isn't my case. And Khouri and Keating sure like their Campath.

Kipps just doesn't believe that last CT report. I told him that I had 4 different radiologist read it, and he still has his doubts.  He pontificated and I don't disagree that radiologist like to be pathologists and internist too.

Assuming these nodes have really grown (which is where I start), what the heck are they? 

Normal fluctuations? I have my doubts that normal fluctuations would have seen growth over three CTs spanning a full 6 months. But maybe.

An unknown viral culprit?  That could also explain my fatigue.  That would be more good news. Dr. Kipps believes that in that case IVIG might help my fatigue. It has a track record.

It could be telling us something worse. Post transplant lympho-proliferative disorder (PTLD)? This is the path that Dr. Furman suggested and Drs. Rai and Forman rejected out of hand. My lab work-up was negative, but that doesn't really rule it out. 

The dreaded Ritcher's transformation (RT). I am just too well for that, aren't I?

So the best way to tell according to Dr. Kipps, is to repeat the CT soon and see if they are growing. Or not.

If not, no worries. The nodes were nothing, or my vegan diet, Zeolite, digestive enzymes, and flaxseed oil has beaten them and with them any trace of my CLL into submission.

We can all relax, for a long time, G-d willing.

If yes, then the next step in a BMB to see if my CLL is still gone, gone, gone. 

If the BMB  still shows MRD-, and my nodes are still growing, that's where things get weird, and scary.

Maybe then Furman and Kipps are right. Maybe it isn't CLL in my nodes. And  many of the immuno-suppressive treatments used to treat CLL would make PTLD much worse. And wouldn't touch RT.

That means a none too easy mesenteric node biopsy because we need a sure diagnosis before we start a treatment. I am not liking the sound of this. That could lead to all kinds of risks and complications.

If both the nodes have grown and the CLL is back in the marrow, I know the story, and the story lines leads to transplant two. And I could ask myself, what advantage was served by forcing to expose my hidden cards earlier than needed in the game. Is my chance at a second CR improved? Probably, but at what cost?

Maybe that is why the wise Dr. Rai told me to tell Dr. Forman to stop with all the CT scans.

Here I am back in the usual CLL place: conflicting advice from world experts.

I think I am NOT going to think about it for awhile and wait to see if a light goes on or my hand is forced.

The best advice I got from Dr. Kipps, and we can all agree on this one:

Don't do anything stupid.

For me, that means sitting on my hands for awhile.

Constant Comment

You must read the eloquent and heartfelt comments on my last post.

Please remember to email me at bkoffmanMD@gmail.com if you want me to respond.

To my friend who is a fellow amputee, having, like me, lost his 11 q arm (chromosome) in the CLL mine fields, and who also has growing nodes, let me suggest that there may be ways to flush out the cancer cells from where the sweet "nurse cells" are keeping them safe from all the poison arrows we can hurdle in their direction.  With AMD 310, or Cytoxan or GM-CSF we may be able evict those no goods that just want to live forever in a nice warm gut node while eating us out of house and home. With coaxing, we might get them out into the blood stream where they must take their medicine like a cell with no resuscitation from their posse. Out in the open, they will be dropping quicker than the value of a share in Madoff's hedge fund.  

I think MDACC has a study using GM-CSF  and R.  I am planning to research it. 

Canaries in a Cat Scan

I have already talked with all my kids, so here's the news, again in the form of a gently edited letter to protect the identity of the recipient.

Details, commentary, the  expert opinions, and the path ahead will follow soon

Dear Friend,

Well, I am not waiting for clarity or good news or even a sense of direction to write again.

My bone marrow biopsy was perfect. Not only am I cancer free down to the last drop, but back to normal. My blood tests are all boring (boring is good in my line of work).

Then the CT scan had to gunk up the works. One of the privileges of being a doc, is that I get to see the images as the radiologist (he like being call rad) studies the shadows made by my insides. Like the shamans reading chicken entrails, but hopefully with a better batting average

At first it looked OK, then there were two suspicious nodes in my gut, but not so definite that a second quick scan might add more info, which showed that it was actually only a knuckle of bowel and all is well, except that with a third look and a second pair of eyes they really are nodes after all. What a roller coaster ride in real time. The biggest node is only 2.2 cm x 1.7 cm. Barely pathological, but clearly growing. Just two 2 stupid nodes are bigger now than on the images from Dec 1 last year. The glands in the armpits, chest, pelvis, groin, and even all the other mesenteric nodes are stable or shrinking.

But the rain's gotta start at some corner. Those two mesenteric nodes are my canaries in a coal mine.

I have left the land of remission and entered the land of relapse. Or at least my toes are through the door. There is still a sliver of a chance that these aren't yellow canaries but actually are red herrings. Pray for me that I am already cured, but my will is being tested.

I am still coming to terms with this all means. Certainly more chapters in my book.

Hopefully the leukemia gurus will have answers, but I think I already know what they will say. Redo the transplant, with a bigger hammer. Bummer. I feel like a bad schoolboy: Brian, you will do this over and over again until you get it right.

Well, at least I have choices and the energy to pursue them.  And with a clean marrow, much time to weight my options.

Some good news:

My son Will was juried into the very competitive Laguna Festival of Arts. At 20 he may be the youngest artist ever accepted.

Our two ton sculpture finally made it into our front yard after years in storage. The house feels more grounded. Now yours isn’t the only house with a playful entrance.

Patty and I are tickled about scoring tickets to hear Leonard Cohen in San Diego. He sure delivers his songs on the NPR podcast from New York. Check out http://www.npr.org/templates/story/story.php?storyId=101034642

Be well.

Brian