Friday, March 30, 2012

PCI-32765 and Ofatumumab Trial Update: Sirens blare and more rashes and sore muscles

I beat the storm back from shul where I said Kaddish for my father. The severe weather sirens wailed a few minutes after I enter the house. Right now, the thunderclaps are right overhead and the lightening is like a 60's strobe show and the rain is falling in torrents.

This time I knew what those sirens meant and what to do to be safe.

Wish I could say the same about my new rash on my left arm.

My left elbow has been sore since I worked out at the gym three days ago with a sweet college student as my trainer. It got a bit worse when I returned again yesterday, but with the dexamethasone aboard for my third infusion from one day earlier I was feeling no pain.... until last night. Been swimming, and enjoying the jacuzzi and sauna too.

Late last night, my elbow stated to swell a little especially up into my medial triceps where my muscle was so sore. It was bright fire engine red with sharp borders, like a welt or hive. And the pain in my arm increased.

The flaming redness faded over a few hours, but a faint flat confluent pinkish rash now reaches from nearly to my wristband more than half way up my triceps and is spreading.

Dr. Byrd's very kind and smart PA, Margaret thought it might be a skin infection. Heck, my immunity is zilch after the steroids suppress everything and the ofatumumab decimate my B cells. And oh yeah, I have CLL.

I don't think the culprit was the IV. It doesn't look or feels like that kind of inflammation. But a micro abrasion at the college gym, a known popular gathering place for germs, could have lead to a staph or strep infection. The sauna and jacuzzi are suspect too.

Like a good patient, I started on the prescribed dicloxacillin, an old school narrow spectrum oral penicillin that has enhanced activity against staph, but not MRSA.

Better to be safe. That is if the dicloxacillin will make me safe. If we are treating the right thing.

After initially resisting the diagnosis of cellulitis, I am now pretty convinced and worried that if it doesn't turn around soon, I may need IV antibiotics.

I saw Dr. Byrd last on March 19, got bad news later that day after he had left, and will not see him again until April 11 at the earliest to discuss what it all means.

Frustrating, but I understand he may want to sit down and talk face to face in a non rushed setting to give me his experienced perspective.

This is no fun.

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Wednesday, March 28, 2012

Update on the trial of ofatumumab and Ibrutinib


Here is an update on ofatumumab first part of my ibrutnib trial at OSU. I do this for for 5 more weeks the on the 9th week of the trial, I finally get my first taste of ibrutinib (PCI-32765). Can't wait.

Bad news:

I don't have common mouth numbness and tingling after three doses of ofatumumab, but my liver function tests have climbed a bit. The ALT is worst at 98 (almost 3x normal), but the AST and LDH are also up but not even twice normal . These are relatively mild changes and only found this one time. I was screening for hepatitis of course before starting, I don't drink anything stronger than green tea, and I avoid tylenol. Heck, I avoid everything. I am on a ton of meds that can effect the liver, but nothing has changed in years.

Even after my transplant, my liver tests stayed boring, in fact toward the very low end of normal. There was a much smaller rise in only was AST when I returned from China, but that was short lived and was trivial. Hopefully the same adjectives apply to this too. Maybe I don't take well to "foreign " foods.

The package insert doesn't mention it. But there isn't much on the common oral neuropathy either.

Generally side effects in drugs are not discovered until they get used by a lot of sick people.

Hence the morbid joke: Alway use a drug when it' s new while it still works and before we find out all that is wrong with it.

Lab next week's lab with see if it's a nothing blimp or perhaps a trend.

Good news:

Eosinophils are falling, almost back to normal (700). CBC is pretty normal, and the rest of the chemistry panel is good to go.

CLL is one weird disease. Full of blind spots and unexplained good and bad twists and turns.

Very good news:

Nodes are smaller. Definitely not gone, but definitely smaller, and my GI symptoms are better.

Could the tumor kill and the cleansing action of the liver be the cause of the increases in AST, ALT and LDH? My white count was normal going into the trial and still is now.

Any other CLLers seen a bump in the liver tests with ofatumumab?

Disappointingly, I did not get to talk with Dr. Byrd so I don't have his take on this or on some much bigger and impactful issues and decisions that I am facing.

So I am still chewing on it and trying to round its corners as I move forward.

And I keep my mantra going: Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react, Under react.

Slowly and with awareness.

Nice n' easy does it every time (with thanks to BERGMAN, ALAN / BERGMAN, MARILYN / SPENCE, LEW and of course Frank Sinatra).

Please enjoy the linked video. I sure did: the chairman of the board and Gene Kelly together.

Ah, that's better.

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Monday, March 26, 2012

PCI-32765 or Ibrutininb and why the great responses in CLL

I almost never just have a strictly medical post, but I thought this was such a clear and concise explanation of how ibrutinib (I better get used to PCI-32765's new name) and GS-1101 (another new name, this time for for CAL-101) that it needed to be shared by those considering one of these new agents for treating their CLL.

Dr. Rai has more experience than anyone in treating CLL and he has no time or tolerance for bogus claims or hype, so I deeply respect his opinion.

That doesn't stop me from questioning his argument in favor of combination therapy.

First. it is too early to know what is best. Dr. Wiestner at the NIH is looking at a single agent therapy and others including Dr Byrd at OSU and Dr. O'Brien at MDACC at combinations.

Second, I worry about powerful chemo selecting out the most refractory clone.

And third and most importantly, I believe that these new small molecules portent a sea change in how we treat CLL with the depth of remission not being the measure of success, but rather the duration of the response.

Let me know what you think.

The original article in Blood can be found here:BLOOD article on ibrutinib.

Thanks to Blood and HemOnc Today.

It is an exciting time in the world of CLL.

9 0Posted March 25, 2012

BTK inhibitor linked to CLL regression

de Rooij MF. Blood. 2012;doi:10.1182/blood-2011-11-390989.

The Bruton’s tyrosine kinase inhibitor PCI-32765 demonstrated inhibitive properties in primary chronic

lymphocytic leukemia, according to recent results.

The researchers based their hypothesis on the premise that small molecule drugs that target the B-cell antigen receptor (BCR) signalosome demonstrate efficacy in B-cell non-Hodgkin’s lymphoma. One such drug, the Bruton’s tyrosine kinase (BTK) inhibitor PCI-32765, also demonstrates a rapid and sustained reduction of lymphadenopathy accompanied by transient lymphocytosis in CLL. This reduction is reversible upon temporary drug deprivation, according to the researchersThe researchers hypothesized that the clinical response induced by PCI-32765 reflects impaired integrin- mediated adhesion and/or migration.

In the current study, it is demonstrated that the drug strongly inhibits BCR-controlled signaling and integrin alpha-4 beta-1–mediated adhesion to fibronectin and vascular cell adhesion molecule-1 of lymphoma cell lines and primary CLL cells, according to the results.

It also has been shown that the drug is an inhibitor to CXCL12-, CXCL13- and CCL19-induced signaling, adhesion and migration of primary CLL cells.

“Our data indicate that inhibition of BTK by PCI-32765 overcomes BCR- and chemokine-controlled integrin-mediated retention and homing of the malignant B cells in their growth- and survival-supporting lymph node and bone marrow microenvironment, resulting in the clinically evident CLL regression,” the researchers concluded.


Two important new drugs have attracted the attention of colleagues all over the world who treat patients with CLL. Both PCI-32765 and GS-1101 demonstrated an extraordinary level of activity when each was used as a single agent in previously treated CLL patients who had bulky lymphadenopathy, and had relapsed or refractory disease. PCI-32765 is an inhibitor of BTK, while GS-1101 is an inhibitor of PI-3 kinase delta isoform. These kinases are considered to be highly active inhibitors of BCR signalling and chemokine networks. The paper by de Rooij and colleagues provides clear and convincing evidence as to how PCI-32765 actually works. These researchers,by meticulous and disciplined work, demonstrate that this drug acts on the micro- environment of lymph nodes and bone marrow where the leukemic cells can live safely and proliferate, an important mechanism for maintenance and progression of the disease. When exposed to PCI-32765, the leukemic cells can no longer hide in their safe harbors of lymph nodes and bone marrow, and they also can no longer continue to proliferate. Being deprived of adhesion-capabilities, these leukemic cells must, therefore, migrate into the circulating blood. That explains why the bulky lymph nodes shrink in size dramatically and rapidly when the patient starts taking this oral medication. This paper also makes it clear as to why the numbers of lymphocytes in the circulating blood increase equally dramatically,at least initially, while the lymph nodes are shrinking. Finally, this paper explains why it will be important to move from using PCI-32765 as a single agent and toward combining it with a monoclonal antibody or chemotherapy, if a lasting and good-quality remission is the desired objective. The leukemic cells pushed out from the lymph nodes and other tissues are eminently killable by cytocidal agents while they are in the blood circulation, where they no longer have the protective chemokines that allowed them to resist while they resided in the lymph nodes. In my view, this is an important contribution that explains the mechanism of action of the exciting and promising new drugs in the treatment of CLL.

– Kanti Rai, MD

HemOnc Today Editorial Board member Disclosure: Dr. Rai reports no relevant financial disclosures.

Copyright © 2012 HemOnc Today. All rights reserved.

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Thursday, March 22, 2012

Spiritual Teaching about Food

I have much to tell and have had a rough time with persistent problems with my muscles. Pretty intense pains at time that make walking even a few steps a frightening prospect. No fun.

But the biggest news is some discouraging findings that I am still digesting before I share here. I need to get some perspective.

I need to under react.

So here is something about two of my favorite topics: food and spirituality. Something else to divert my attention

When Swami Vidyatmananda, a westerner that had joined the Ramakrishna order was a probationer, he went to India to visit the headquarters of the Order. One day, he decided to leave the ashram in the outskirts of Calcutta and go into the city for the day to do some shopping. When he told his superiors his plans, one of the swamis inquired as to what he would do for food while he was there. He told the swami that he would simply go to a hotel to eat (thinking to himself that he could get a good western-style meal that way). The swami responded to his idea by suggesting that it would be better if he went to the order’s ashram in the city for his meals and offered to phone them for him. The swami then went on to explain that the members of the Order avoided eating in hotels and restaurants because of the low spiritual vibration of the food there.

“Food not prepared with devotion, not prepared with the idea that it is to be offered [to God] in the shrine – but just devised impersonally for making money by people with their minds full of gross thoughts – can adversely influence your spiritual growth.”

In one of his teachings, the Baal Shem Tov asks the question: the body receives nourishment from the food we eat but from where does the soul receive its nourishment? The answer that he gives is that the soul receives its nourishment from the Divine spark that is in everything; for everything in the world has been made by God and therefore is filled with His Spirit.

When we eat, it is our bodies that take up the physical nourishment that is in the food. However, if we recite a blessing with intention before eating, and turn our minds towards God, then it is our soul that receives nourishment from the Divine spark that is enrobed in the material form of the food.

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Tuesday, March 20, 2012

Dealing with "this mental roller coaster"

Here is what I believe is an important exchange between me and a friend with CLL.

I think it a critical teaching for anyone in a health crisis, including myself.

I am very grateful to the letter writer for allowing me to pause and formulate a response that I hope helps him and I know helps me.

This is looping around old themes, but sometimes I am a slow learner or I just forget what is important and what is not.


On a personal note - are you aware of any studies that have been done or help that may be available for those who have been on this mental roller coaster? When on "high alert" the other things of life tend to get shoved aside. Now that the alert level is lower it's as if I don't know how to behave.
The transitions between high alert stages and the low alert stages take too much mental energy. I need to find a middle ground to function in.
Any thoughts?


My response:


Boy oh boy do I hear you loud and clear. Shifting gears from crisis to normal is tough.

I bet there are studies. I just don't know the data.

If it's overwhelming, see your doc. He can help with counseling or even meds.

But I bet you can by with this plan:

My advice is to under react to everything, the high, the lows.

Don't get too excited by the good news and give yourself time to digest the bad news.

CLL is big actor is life's drama who may try to steal every scene, but it is not the lead performer.You are. You are also the director and the producer. You get to decide who gets the spotlight and the most attention. You can focus on the ones you love and the good works you do and your faith in a greater power and purpose. You can get lost in the joys of trivial pursuits or lofty projects. It's all OK.

You can't control the rascally CLL as much as you would like, but you can control how you react to its hamming it up. Believe me. I am dealing with a few very hard knocks myself these days, and I am just collecting the data, chatting with my friends using my support network of other CLLers and trusted confidants, and cooling my heels before I make a move. Under react.

Trust me on this. This is a great teaching I got from a very dear friend, a doctor who has fought and won a big cancer battle in his life. Under react. Take some time and get some distant. Let things digest. CLL is almost never urgent.

Love is urgent. Family is urgent. CLL is not urgent.

Stay strong

We are in this together


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Monday, March 19, 2012

Death in the PCI-32765 trial

I guess I should share what I have just confirmed today from the trial staff.

One "young" participant in the trial in my cohort recently died of viral pneumonia. What I found out is that he had no PCI-32765 and only a couple of doses of ofatumumab. He had other "medical problems" and seems to have had iffy immunity prior to going into the trial. Long term steroids may have been a factor. So the PCI-32765 or ibrutinib was clearly NOT the culprit.

Still, he took a chance, entered the trial and died. I am sure he had to do something and this was his best choice. Mine too.

Tragedy is suffering without meaning. What is the meaning of this loss? So sad to lose this stranger just a few steps ahead of me in this journey.

Clinical trials are full of incalculable risks. How do you want your danger served up: known or unknown?

Infection risk seemed to be very underplayed. Immune suppression is built into mechanism of action of both the ofatumumab and the PCI-32765 and can't be tweaked out. We are playing with powerful weapons that are not quickly turned off and on. Although they are targeted therapy, the targets do more than just slow down the cancer cells. The collateral damage may miss the marrow and the liver and the lungs and the T-cells (unintended targets of other small molecules and MABs), but both trial drugs hit the humoral immune system and the ibrutinib probably does something nasty to the some patients' platelets too.

Still, I needed to something and this trail still makes the most sense

CLL sucks. Cancer sucks.

Options are good.

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Sunday, March 18, 2012

Tornado Warnings, sore hips, and my broken internal clock


Out for our dusk walk and we keep hearing sirens. To the right the sky is bright blue with fluffy light clouds backlit by the setting sun. Perfect.

Ahead to the east. black clouds against grey sky moving fast with lightning flashes and loud thunder every few seconds. Coming closer. Ominous.

The air is strangely calm.

We cut our walk short and hustle home just before the cloud burst. The thunder is hammering at the windows.

Tornado warning in effect. One aiming at the airport as I post. It's always something.

I am still up to 3 AM most days and have trouble waking in the morning. Can't seem to be able to reset my clock even after a week here in Columbus.

I have several absolute final must complete by tomorrow assignments due that are not helping my adjustment as I tend to do my best bursts of work late at night, at the last moment.

And I have this mysterious annoying left quadriceps pain that comes and goes with vengeance and abandon, leaving me crippled with pain at times and completely fine and wondering if I am imagining this all at other times.

When I stand up (sometimes only) there is excruciating pain in my left lateral quads about 2/3 of the way down to my knee. The pain always disappears when I am sitting or lying down, and most but not all the time after a few steps. Sometimes it lingers for an hour while I am up. It radiates down almost to my knee and up to my groin.

Mornings are best and so are the ends of the day.

I never know if I am going to hurt when I get off the sofa or out of the car.

I worried about avascular necrosis of the hip from all the steroids, but my passive range of motion is good and my hip only hurts with flexion which it not classical.

There is no warmth or swelling and it is so intermittent so I doubt it is a deep vein thrombosis.

It feels more like a deep unremembered bruise that is jamming the quad mechanisms and I have to wait for it to release. My lateral tenderness fits with that too.

But why is it not getting better and arguably worse after 5 days?

The intensity and the unpredictability of the gotcha is making want to sit more and walk less- not a good thing.

Tomorrow is another whole day at the infusion center with all the premeds of steroids and benadryl and more again. And it will be my first full dose of ofatumumab. I am not thrilled.

But I soldier on and Tuesday I am going to the main 600,0000 square foot (yea that is more than half a million square feet in one of several facilities for the students at OSU) recreation facility for an orientation to the workout equipment. Bought a new speedo for the 4 swimming pools.

And Tuesday night I have tickets for a hockey game.

Met some lovely other lab rats in the trial several weeks ahead of us who are doing great.

And spring is definitely trying to make its presence felt as evidenced by the photo from the walk in woods at a nearby city park.

More critical PCI-32765 trial news tomorrow once I get official confirmation from the trial staff.

Eery sirens or no sirens, bad news or not, I am here for the duration.

Wish I had matches for my candles. Glad to have a roof over our head. Should we head for the closet?

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Tuesday, March 13, 2012


Beaver Mischief
(the mischief maker swam off just before I got his photo)

After a mostly sleepless night and a wasted day (sounds like back in college, but not nearly as much fun), I am quickly crashing from my "roids" driven high. Patty and I did manage a lovely short walk at the wetlands a mile from here where we saw beavers and Canada geese and a million other birds before the floor dropped out from under me and I stumbled home. The scene made me long for my birth land, O, Canada, the true north strong and free. Thanks for the tip, Wayne. Much appreciated.

The winter seems to have vanished in Columbus, which is just fine with me. What a difference a week makes. Last week it was snow flurries and howling winds. This weeks it's golf and biking weather.

But I am getting dreamy and have work to do tomorrow, so I forced myself to not nap today so I can sleep tonight.

Just because I teach others about sleep disorders, doesn't mean I have to demonstrate them.

Goodnight all.

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Monday, March 12, 2012

Don't do anything RASH

First day of ofatumumab at OSU, so I only received the amazing slow test dose, still I was there almost 12 hours. They are very diligent and careful. Turns out it was a wise precaution.

The staff were all sweet and professional. Couldn't have been nicer.

The fun really began when I broke out in a itchy hive like rash (worse they have ever seen) from head to toe about 4 hours into the infusion when I reached the maximum dose. This was despite the pre-meds consisting of 20 mg of Decadron (a hefty dose of a quick acting steroid), Pepcid (used in this case to block the histamine 2 or H2 receptors), Zyrtec (another antihistamine), Tylenol and 50 mg IV push of the first generation OTC antihistamine/sleeping pill Benadryl (enough to push me straight into la-la land). So it wasn't until I woke up to use the restroom and looked in the mirror that I saw my most impressive splotchy red face and neck. By that time the rash was everywhere. I called my nurse and they immediately stopped the IV and soon I was the hapless recipient of yet another 50 mg stupefying dose of Benadryl IV push and the amped up supercharged power of 50 mg of Solucortef (another quick acting steroid). 30 minutes later the rash was history, the IV restarted. I finished treatment without a hitch around 7:30 PM.

Ofatumumab causes more reactions because it a more active antibody so I can't complain,

Still all the Benadryl will make me sleepy stupid for the next several hours and all the steroids will keep me alert and ready for action all night for the next day or two. Then the crash until my adrenals recover. My body is a little confused as to what to do next.

Another minor issue: I will not be able to tell immediately when my nodes shrink if is it from the wallop of the steroids or the ofatumumab and besides I am way too dopey to think about it.

Finally before all this started, my eosinophils were really high about 2.500 and even appeared in excess in my marrow. More on that when my mind is clearer. More on other lab later too.

Still not a bad day. Got through the test dose. Found the way to the center despite the rain and the construction and the lack of sleep. found a place to park, met nice people, signed onto their patient portal. got my blood and IV with one poke, and dozed for hours.

And this may just be wishful thinking (or the steroids), but I do believe that my nodes are already smaller.

So despite this still not being a therapeutic dose, this is the official star, my first cycle of my next amazing CLL adventure. And its in the bag or should say out of th bag and in me now.

Let the games begins.

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Thursday, March 8, 2012

Virtual Cancer Buddy

Hi friends,

I have been dreaming.

Actually at the urging of a forward thinking doctor friend, I have been wondering what might be in the best interest of all cancer survivors in a high tech approach to managing what is increasingly being understood as a chronic disease. That is certainly the case with CLL as the new therapies evolve.

I am envisioning something much more than a simple excel sheet that tracks labs. What I want is some kind of virtual helper that electronically nudges me to take my meds on time and do my aerobics. I don't think this is a fantasy. Hospitals are already exploring using patient portals to help manage heart failure and diabetes after discharge. Cancer care has a more distant and broader horizon, but I still think it can work.

What would you want included in this virtual cancer buddy?

Here are some thoughts I had in no particular order.

Contact info for providers?

Personal reminders of meds, exercise, appointments, lab?

A patient portal to ask questions or review labs?

Annotated interactive med lists that highlight possible risks, adverse events, and interactions?

Lab flow sheets with graphs and alerts?

Vital sign flow sheets?

Diet and exercise charts and advice?

Stress reduction techniques?

Glossary of terms?

Information for family and other caregivers?

Help with the decision process?

"Red flags" and what to do if you have one?

A "Siri" that answers your questions?

Please email me or post your thoughts and suggestions. Do you agree with my list? What would you add or delete? Dream big. Forget being practical. What do you really want? I will organize them and present them here and to my contacts in the hospitals systems and see if I can get some traction. At least I can make sure someone is hearing us.

I have posted this identical request on CLL at ACOR and the CLL Yahoo group and got very valuable responses that I am trying to tie together, but my blog reaches different readers and I want to hear what you have to say.

We are all in this together.



Wednesday, March 7, 2012



Here is a link to the first of several CME activities that I put together out of the video recording of my interviews of Drs. Kipps, Pagel, and Wiestner at ASH, 2011. I am hoping to do the same for ASCO 2012 in Chicago if I can get the funding support. Any ideas?

Please go to and select the CLL recognition link. You need to answer the pretest questions to get to the videos and text.

There is much more to come, but these are a lot of work. I am pleased with how the first one turned out. My son, Ben was the camera man and did the hard work of all the editing.

I am committed to teaching primary care providers about blood cancers, especially CLL. I believe they can play a critical and unique role in the patient's care.

On a personal note, I am back from my screening visit to OSU and will be flying back Saturday to Columbus Ohio to start my weekly ofatumumab x 8 then and only then to I get to start my PCI-32765. My counts remain good, but my nodes are definitely on a slow upward march, so it will be good to get into therapy.

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Monday, March 5, 2012

Screening Columbus, Ohio

I wish I could share some news, but after a day of being poked and probed and scanned, and starved, all in a very pleasant and efficient way, I am heading home only knowing that my CBC remains goods. all the other labs, biopsy reports, and CT finding are pending. They need to know I don't have some hidden disease, infectious or otherwise, that will suddenly flare up when my immunity takes a hit.

Here's what I do know.

My hemoglobin was a near normal 13.6, my platelets were low for me but still great at 329,000 and my ALC was 2.6. All good, very good in fact.

The only weird finding was my eosinophils were 1,100, more that double normal. These relatively rare granular white blood cells are usually elevated with allergies or some strange parasitic problem. Or maybe it's a lab error. I will have it repeated on Friday, and that should give me an answer. I seem to recall in bumping up before and being nothing.

I can't wait to get started. Next week, ofatumumab.

But first I need to get up at 3:15 AM to catch a 6 AM plane to Chicago on my way to Oakland to see my granddaughter before my immunity is hobbled again. Then visiting a little girl who goes to day care may be too risky a proposition..

Seeing her is my reward for all this ......trial.

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