Control, Not Cure: A New Path Opens Up Four Years Later - Transplant Then, BTK Inhibitor (Ibrutinib) Now

Four years ago today, I was admitted to City of Hope for a first remission hematopoeitic stem cell transplant. It was and still is the only possible path to a cure for CLL.

The only way to say: "I used to have cancer."

At that time not only was CLL incurable outside of a high risk transplant, there were no options that had even been shown to prolong life.

Now we have proven that FCR can add years to our life. The same is probably (but not certainly) true for BR and perhaps other very effective chemo-immunotherapy cocktails.

But FCR is hard on the marrow and not a great choice if you are older or more frail or have an auto-immune history such as ITP (as I do) or AIHA or if you are 17 p deleted or otherwise F refractory.

As those or you who have followed me from the get-go know, I failed my transplant because I rejected the graft. I was too healthy from an immunity perspective. With no graft aboard, I never had any of the desired graft versus tumor effect. Within a year I had relapsed and needed treatment again for my ITP and later my CLL.

The transplant didn't cure me, but it didn't kill me either. What it did do was buy me time until the game changing new therapies showed up.

Because of the brave souls who entered into phase 1 trials of an unproven and radically different  approach to CLL, I was able to follow their trail into a more mature and certain trial for a tyrosine kinase inhibitor, in my case ibrutinib (formerly PCI-32765) that blocks a pathway that is jammed in the on position inside my cancerous clone. It keeps telling my cells to proliferate and never die.

Not a cure, but a promise of longterm control with a very manageable downside.

There are other similar small molecules and pathway blockers and promising new antibodies and immune modulators out there that are changing the way we will approach CLL in particular and cancer in general.

Four years after I entered hospital on my high stakes gambit to be rid of this cancer once and for all, I am shifting gears. My transplant failed and since I never engrafted, it is almost as if it never happened. All my benefits (and risks) were from my one week of high dose FCR conditioning.

Today I am amazingly healthy after seven years of a battle with a persistent and aggressive enemy, but  now I have a kinder gentler approach and it seems to be working. Let repeat today's theme: Control if not cure.

I have made the shift. I was lucky to be able to see how the paradigm was changing and make a move. 

I can now clearly envision a new future that was just a distant speck on the horizon four years ago.

I can live with that.

G-d willing, for a long, long time.

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.

We WON

ME HOISTING THE FLAG AT GAME 6 OF THE STANLEY CUP FINALS

The ibrutinib is working. I am working on a post detailing shrunken nodes and healthy blood counts and improved energy.

Honest I am but I have my priorities straight. 

That good news pales in comparison to the sheer joy of being at the game where the Kings and their patient fans finally got to hoist Lord Stanley's Cup. Been a loyal fan for 22 or their 45 year wait.

I buy season tickets so I can go the playoffs. My cancer trial made me miss going to all but two games in their amazing record breaking Stanley Cup run. 

But those two games were thunderingly joyful.

 Game 3 in LA -where they won 4-0 and tonight at home where they won it all.

They could have clinched in game 4 when I was in Ohio or game 5 when they were in Jersey and I was in Orlando.

But as it turned out,  they waited until I was back in SoCal to claim the big prize. And in such amazing style. 6-1. Three goals scored on the major penalty in the first period.

I am so happy. People were crying at Staples Center.

Sometimes delays are good.

Sometimes we get a lucky bounce.

Sometimes things just workout.

I am feeling like such a lucky man tonight. I am getting my health back, I have love in my life, and the Kings won the Stanley Cup.

I CAN'T STOP SMILING!

Celebrating with a organic vegan muffin and raw vegan coconut milk "ice cream".

GO KINGS GO!

Part 2 Is there a doctor on the plane?

It has too busy with travel and treatment and lectures and the Stanley Cup Finals (GO KINGS GO) to blog. I should be able to catch up more with lots of good news about me and ibrutinib from rainy Orlando real soon


But first when I last left you, I was walking to the back of the plane to see who needed medical attention.


To see if I could help?


To see if was putting myself at risk/


What I found in the last  row was a man in his early 50s acutely short of breath with an oxygen mask on, very afraid for his life.


Less than a minute after arrived, t was being asked should we divert  the plane to Las Vegas. (What power. I should have said that Hawaii was a better choice).


I took a brief medical history. Turns out my patient suffered from chronic inflammatory demyelinating polyneuropathy (CIDP). I had had one patient with that rare disorder years ago. It is a bit like MS in that the sufferers develop an auto-immunity against their own myelin sheaths so the nerves, especially the motor nerves getting weaker and weaker. If CIDP involves the respiratory muscles, life threatening shortness of breath is a rare but real possibility. Pneumonia can also occurs with a decrease cough reflex.


He denied chest pain. No calf swelling or tenderness. No cough or fever. No new new meds or foods. No history of asthma or severe allergic reactions. No other major medical issues.


I used the emergency stethoscope that the steward provided. I could hear no air moving in and out. A very very bad sign. Then I listen to the heart. Again I heard nothing. But my patient had a normal pulse.  And he was not turning blue or had any altered mentation. In fact there was none of the classic signs of respiratory distress- nasal flaring, using accessory muscles, tracheal tugging. Maybe the CIDP was obscuring them? I retrieved my own stethoscope from my seat. Still nothing. Then I listen to my own heart. Nothing. The problem of course was the volume of the ambient noise, not that my patient had no air entry into the lungs and that his heart had ceased beating. I didn't asked if they could turn the engines off for a few minutes so I could listen in the quiet, but the thought did cross my mind for a moment.


He had an infusion of IVIG the day before and was worried about the effect of flying so soon afterward. Now I have great personal familiarity with flying right after IVIG. I have done it dozens of time without a blink or blip. I plan my long foreign trips around my IVIG and try to get it just before I leave for  exotic lands. He was very reassured by this.
.
We chatted more. He was able to talk without gasping or halting. He was felling better, less air hungry. We walked up to first class. His gait was weak and his hands shaky. CPID has devastated his muscles.


No need to divert the plane.


We talked about his family, my leukemia, his treatment. The oxygen mask came off. He was smiling, relaxed, feeling OK again. I gave him my contact information.


His panic attack was over. I still had the paramedics meet the plane and take over his care. After all I had yet to really auscultate his lungs. I could have missed a pulmonary embolism or a cardiac issue or....


That afternoon back home at last, I got a call from a dear friend, a fellow family doctor with CLL living in Canada just admitted to the neuro-ICU with chronic inflammatory demyelinating polyneuropathy. Was it related to the weird immune system us CLLers share? Was it totally unrelated? Seeing as no-one knows the cause of CIDP, it is anyone'e guess.


What are the odds? Two cases of an exceedingly rare disorder on the same day. 


Synchroncity? Where is Dr. Jung when I need him?


I had done my doctorly thing. It ended well. I could talk to my Canadian friend with some fresh knowledge of CIDP from the research I did after I landed.


The steward asked for my frequent flier number as I was leaving the plane. Maybe I will even get some miles out of just doing what I do.


One last puzzle piece. When I got down to baggage claim, another doctor who was on our flight walked up to me too thank me for jumping in. He was being treated for cancer and didn't want to take the risk of offering to help due to his lowered immunity. 


Don't be judgmental.


We all make decisions. If the patient that I had found at the back of the plane had not had a panic attack on top of a rare neuromuscular disorder, but was suffering from a much more common condition such as severe asthmatic bronchitis, putting anyone such as me or the more reluctant doctor at grave danger and with little to offer in the way of help, his decision would have been the correct one, not mine.


It is good to be lucky.


I promise more lucky news soon from my ibrutinib trial at OSU.

Weddings Come First

I have been celebrating a wedding for the last three days and that takes priority over CLL and airplane drama and the latest news.

It was the reason I missed ASCO where I would have loved to have attended the oral presentations on ibrutinib by Dr Byrd and others and wish I could have heard Kanti Rai's acceptance speech for the award he  received in recognition of his lifetime of monumental achievements. And to have just run into all the other CLL gurus I am privileged to know. Do some more interviews. Digest more. Share more.

But weddings come first. The information from ASCO will all be available soon enough.

Nothing new to share about my response.

Back to Ohio next week for my first CT scans since starting on the ibrutinib. That will tell a tale.

Will finish my airplane story, soon, I promise. But  not tonight.

Having cancer gives you a whole new perspective: A medical emergency on the flight home and a friend with a new possible complication of CLL: Chronic inflammatory demyelinating polyneuropathy (CIDP)

I last posted from the gate at O'Hare about how tired I was on my trip home from Columbus.

Soon after that is when it started getting interesting.

I managed to stay awake long enough to board the plane, but was soon I was sleeping, wearing my N95 mask, feeling lucky and comfortable with the extra leg room in my exit row window seat with the rare joy of no-one's elbow in the middle seat next to me, when the call went out: Is there a doctor on the plane?

There was no choice. There was no decision to be made. There was only one course of action: to try to help.

A medical degree is not disposable and can't be shed like a worn out shirt.

A call for help demands a response. After all, a complete stranger from halfway around the world,  a Talmudic scholar had tried to save my life by donating his stem cells for my transplant.

I am no Talmudic scholar, so I beg any one reading this more familiar with the backbone of ethical actions for an observant Jew to add their commentaries and correctives, but here is my take.

The Talmud is clear about one's obligations. You must help, but only when it is possible to help. You do not need to risk you life to try to save someone beyond saving. And you are not asked to put yourself in immediate danger to save another.  Inconvenience, cost, and loss of time or money are not imminent dangers and are therefore not acceptable excuses. You may need to pay a price for doing the right thing. So be it. Risk to your own health and well being however is a different story. It is a legitimate and ethical and just plain sensible not to jump into the raging river to save a drowning man, especially if you can't swim.

Neither of these two caveats were clear to me when I heard the call.

After all, anyone with CLL has compromised immunity from the get-go. Was the person I was being asked to help contagious?  Was he or she coughing or bleeding or oozing? Was I putting myself at risk? The efficacy of the mask in protecting against infection is suspect at best when the mask is brand new. This one was making a return flight on my nose and mouth. Did they even have latex gloves to protect a good Samaritan doctor?

As to the first question, I wondered as I headed to the back of he plane: Could I do anything to help on a noisy crowded plane with very limited equipment and no real therapies to offer? I had worked my last ER shift over 30 years ago. Not much that I could treat on a plane. I carried a bottle for ASA to help in case of a heart attack. Did they have a epi-pen for a severe allergic reaction or asthma? I didn't. Did they have pressure dressing for bleeding? Not me. Did they have oxygen for all of these? What if it was a GI or GU or an OB/GYN emergency? Premature labor? Any one of those would be a challenge in economy seating at 30,000 feet.

I needed to find out.

I walked to the back of the plane where the patient waited.

TO BE CONTINUED.