Poster Boy for OSU

Here is my 15 minutes of fame as I get to share the spotlight with Dr. John Byrd on the cover of the online and snail mail OSUCCR or James Cancer Hospital and Solove Research Institute quarterly magazine: frontiers.

I found out about hard copies being mailed out to thousands of heme/oncs across the country when my local hematologist, Dr. Sanjay Sharma teased me about the color choice of my sweater. I do think Dr. Byrd and I look pretty collegial. I get that I have been co-opted by the Buckeye Nation and I proudly accept.

It was clearly a honor and a privilege to help promote the good work being done at OSU in general and by Dr. Byrd in particular and to also push participation in clinical trials at the James and elsewhere.

Follow the link to find the actual article on page 14 and you will also find Dr. Byrd in his white coat on page 9 describing some of his lab work. Much good information on CLL research in both articles.

Today, I am being cared for by my own medical group, namely at the St Jude Heritage Medical Group cancer infusion center getting my IVIG.

I am very lucky to have this incredible network of care.

My CBC is already back and remains boringly normal.  No anemia, low lymphocytes and high platelets. Life is good. More results including my critical bone marrow findings to follow soon.

But first, let me enjoy the sunshine of brief moments of fame.

ASH 2012: Dr. Tom Kipps on Genetics, Epigenetics, and Targeted Therapy

In the third of a four part interview with my CLL doctor, Dr. Tom Kipps out of UCSD, we hear him present a vision of the future of "personalized" cancer therapy in general and CLL in particular.

But he also tells us what targeted therapies are available right now in clinical trials near you.

In CLL, it is less about the genetic code and more about the epigenetics. This crucial and relatively recent understanding has been critical in advancing therapies because the pinpoint DNA damage seen in CML such as the telltale fused Philadelphia chromosome are frustratingly less of a glaring target in CLL. However, when the researchers instead started identifying the overly activated pathways in our clonal B cells, the progress sped up in decoding and quickly thereafter, controlling our disease. Dr. Kipps walks you through the difference in these approaches.

Dr. Sharman talks about this insight in one of my prior post, and here Dr. Kipps makes it all easy to understand. He also explains combination therapies, the importance of the new and old generations mAbs (monoclonal antibodies) including 1st generation rituximab, 2nd generation ofatuzamab, and the promise of the powerful 3rd generation GA-101 or another mouthful of a name, obinutuzumab, all directed at CD20, re-use of some drugs already approved for other cancers, and CAR-T therapy

Eleven minuted well spent. Dr. Kipps breaks it all down into bite size pieces.

Learn and enjoy:



Part Four with Dr. Kipps will be coming soon and I still have Drs. Wiestner and Furman in the video vault. ASH 2012 was an amazing meeting, jam-packed with hope and good news for those of us with CLL.

Personal notes:

I am still waiting for my final bone marrow biopsy report from OSU done Feb 5, 2013. FISH and cytogenetics should be back by now, and I hate the suspense.

Back home from studying hematology for hematologists at the 17th Annual International Congress on Hematologic Malignancies – Focus on Leukemias, Lymphomas, and Myeloma in Manhattan and the MDACC hematology board reviews, so I can be more fluent in speaking about the buzz around small molecules such as ibrutinib, ABT-199 and idelalisib in treating other B-cell lymphomas in particular and blood cancers in general.

I will also return to posting more on the personal and human aspects of dealing with an incurable cancer, but for right now, my priority is to get all the remaining ASH 2012 videos online over the next few weeks.

Next weekend, I am off to Washington DC to lecture to the National Sleep Foundation on "The Sleepy Patient". Then I am home for several weeks in a row. Yeah!

In the spring and fall, I will be flying all over the place again teaching other doctors about anemia (MDS or myelodysplastic syndrome that can be a challenging late complication of CLL and some of the chemotherapy used to treat it), gout and thyroid disease. I will be posting my ASH 2012 interviews with Dr. Steensma on MDS here soon.

For any health care providers reading this blog, and to anyone else interested, for another few weeks until March 6, 2013, at Primary Issues, an online medical journal, you can receive ACCME accredited CME on the recognition and early lab testing of CLL or just learn from my article and interviews with Drs. Wiestner and Kipps done at ASH 2011. That San Diego meeting 14 months ago is where I made the fateful decision to enroll in the clinical trial NCT01217749 at OSU that has served me so well.

My love is teaching and my special love is teaching hematology and making sure that the patients and their providers are teamed together to offer the best possible care for each individual case. That's what I want to do more and more.

I am hoping to find some funding do more of these interviews and news coverage for patients and healthcare providers alike, to expand beyond the big ASH meeting to ASCO and IWCLL and more. Next up will be ASCO at the end of May, where I bet there will be important updates on ibrutinib, idelalisib, ABT-199, obinutuzumab and others.

ASH 2012: Dr. Tom Kipps Explains BCR, Chemokines, and the Power of Blocker Drugs

This is part two of my ASH 2012 interview where my doctor, Dr. Kipps out of UCSD, makes the importance of BCR and chemokines to the B cells understandable. Even a vegan like me can understand his Thanksgiving dinner analogy. He too talks about the debt of gratitude owed to all the patients who enroll in the clinical trials.



More to come soon.

On a personal note, I am home a day early from five days in Manhattan at a hematology conference where my family doctor brain was crammed full of new malignant hematology facts and figures so that I can talk about more than CLL to the experts that I am privileged to meet. I was, for obvious reasons, the only family doctor there, and had to check "other" on my registration form as there were not expected any PCPs to show up. If you newbies to CLL think the acronyms for CLL are bad, hematologist are the perpetual masters of an expanding array of coded alphanumeric soups. I was constantly multi-tasking as I was learning the new material and scouring the web at the same time to decode the heme shorthand for all their therapies.

I did take time off to have some gourmet vegan and raw vegan meals at Pure Food and Wine, Candle 79, and Candle Cafe, dance and sing at a neo-Hassidic shabbat service at the beautiful B'nai Jeshurun,

and catch the very last day of the gritty ash-canny George Bellows exhibit at the Met (and of course revisit the masterpieces by Van Goghs and Caravaggios) all artists whose lives ended far too early, but whose influence will be eternal.

Despite the biting cold and the wind that careens channeled by the steel skyscraping canyons, just walking around Central Park (where I saw an extremely rare golden (or red) tail hawk) or by the skaters at Rockefeller Center or inside the bustle of the well preserved centarian, Grand Central Station, or with my fellow gawkers at Time Square, there is no place on earth like New York City.

After a wonderful visit with dear friends in Springfield, Missouri and undergoing a critical and demanding but extraordinarily successful external review for all the medical education work that I do, I had the help of a friend who drove me 80 miles to Joplin, MO to get the very last seat on an overbooked flight out of Missouri before the ice storm hit the midwest (all the local flights were unavailable and the next flights out were likely two days away). 

I got home a day early to warm and sunny California.

Home for a week, then off the Washington, DC.

ASH 2012: Dr. Tom Kipps Explains why Understanding CLL Biology Helps us Focus Therapies: Bcl-2 and ABT-199; as well as my Reporting on the Suspended Trials

This is the first of a four part interview with my doctor, Dr. Tom Kipps, where he unpacks for us the complexities of why Bcl-2 is such an attractive target in CLL.

This is not a theoretical construct, but is directly pertain to a powerful drug that is in clinical trials right now: ABT-199. That power is a double edged sword and I discuss the recent news about the trial suspensions later in this post.

It turns out that of the all the B-cell cancer, CLL is guilty of the greatest overproduction of this Bcl-2 which is a strong cellular anti-suicide messenger. Twin that with the contravening fact that CLL cells also overproduce the powerful pro-apoptotic (programmed cell death) compound BIM. But BIM is held in check by the excess Bcl-2.  Block Bcl-2 and then the BIM goes bam and the cancer cell suicides.

Vey good.

That is where ABT-199 comes in. But I will let Dr. Kipps explains.



Now all this power to take the safety off the suicide bomber inside every CLL cell comes with a heavy cost. If it is too effective, especially in someone with a high tumor burden (read very high lymphocyte count and huge nodes) and /or there is a significant dose escalation, the cell death toll can exceed the body's ability to cope with all the waste produced by the broken down cells. This is the dreaded tumor lysis syndrome( see this nice explanation by Dr. Sharman), and it can not only kill the patient, it can kill the development of a life saving drug.

Very bad.

I have waited until there was a reliable public source for confirmation before posting this information on my blog and I got it today from Bloomberg news.

I quote:

AbbVie Inc., the drug company that split off from Abbott Laboratories at the start of the year, suspended five studies on its experimental leukemia and lymphoma medicine after two patient deaths.

The patients died from tumor lysis syndrome, said Tracy Sorrentino, a spokeswoman for North Chicago, Illinois-based AbbVie. The complication stems from the rapid destruction of malignant cells after treatment that can trigger acute kidney failure. It occurs most often with large tumors such as those found in leukemia and lymphoma patients, according to the National Institutes of Health. 

They continue:

“We have every expectation that these trials will come off the partial clinical hold and we’ll be able to initiate Phase 3 trials in 2013 as planned,” she said. “ABT-199 is a highly- potent agent and can result in the tumors reducing really quickly,” she said. “We are working to refine the dose.”

After the complication was discovered, AbbVie and its partner, Roche Holding AG, suspended the dose- escalation portion of the studies to determine the amount of drug that is safest and most effective, Sorrentino said. The risk stems from the drug’s potency and can be managed if the dose is carefully controlled, she said. 

This is a very powerful oral medication that has a tremendous potential to help even the worst risk patients with CLL. I want to have this option available in the near future to the many of us who might benefit from it, but not at the cost of moving too fast in the clinical trials. I agree that now that we know the danger, we can take appropriate precautions. 

Personally, if  I wasn't already doing so great on my ibrutinib trial, I would not hesitate to enter an appropriate ABT-199 trial once they have the dose escalation reworked. If anything, they are going to be over cautious from here forward.

Hence my prior post on dotting the I's and crossing the T's that was my loud admonition to take it slow with drug trials.

Nice and easy does it every time.

Dotting the I's and Crossing the T's: The Risks of Rushing a Clinical Trial or the FDA Approval Process

I have looped around the issue of clinical trials and the understandable burning desire to get as much early access to these wonder meds in and out of trials ASAP.

Today I am arguing for some painful patience and prudent caution in this rush to judgement.  I am going to point out some of the dangers of trying to speed up trials or cut corners to get drugs to market.

Times are changing fast in the treatment of CLL and we are all looking forward to the promised end of the era of chemotherapy as we have known it for years.

My blog has been filled with top CLL researchers forecasting this brave new world and additional similar interviews from ASH are on their way.

But this brave new world is still at least a year and half and more likely two or three years away, so we are forced to continue to wait for the day when we will be able to simply pick up these magic pills at our local pharmacy.

In the meantime, the only access to ibrutinib or idelalisib or ABT-199 or AVL-292 is through an FDA approved clinical trial.

Not surprisingly, some might want to take shortcuts, and race these drugs through trials and to the market to get wider and earlier access.

Major CLL researchers and patient advocates are also anxious to see these drugs available to as many as possible as soon as possible. Some have spoke powerfully on the need to quickly move the agenda forward and their mounting frustration with the IRB's and the FDA's slow methodical processes. They point out the preventable deaths of those that might have been helped by these new medications, but because many of needy subjects don't exactly fit the inclusion/exclusion criteria for a trial, they are left out in the cold, in a world filled with last years's drugs and treatments.

I get it. I feel it. There are those who need treatment now, but are cut off from the trials and don't want or can't risk chemo.  I have corresponded with many caught in that limbo.  But there are non-chemo options for most. Phase 1 trials are often more forgiving and open.  Also non-trial non-chemo options include HDMP+ R or O, O on its own, or lenalidomide + R,  lenalidomide + thalidomide. Look for something gentle to buy a year or two until the new batch of drugs are available. It may not be ideal, but it is possible and does keep you in the game.

More that one CLL expert has told me that the sure way to ruin a good drug is to skip a step in the process and find out down the line about a foreseeable and preventable adverse event. That is deal breaker for the FDA that will almost certainly send the drug back to square one and will guarantee to make the trip to market slower and more costly. And too often, the parent pharmaceutical company may decide that the hurdle is too high and the expense too great and the potentially beneficial drug dies of a self-inflicted wound long before reaching the finish line. Or if the medication is already on the market, the delayed discovery of a clinical problem is a hanging curveball for the trial lawyers and we all know that when they swing their bats, the ball is headed out of the park and the game is generally over, for better or for worse for the patients left stranded in the field.

Methodical, boring, transparent progress is the only way to go.

Another issue. A common approach used in phase 1 trials has been dose escalation to toxicity. This standard puts pressure on investigators to rapidly keep pushing up doses until something happens. Those somethings are treatment limiting toxicities and include  mild adverse events, but can cross the threshold into a potentially fatal event such as tumor lysis syndrome or a cytokine storm.

Slow and easy does it every time.

Here's a wild idea that might safely speed things up, but it too needs some diligent review.

Some of these new meds might warrant a different approach to phase 1 trials due to their much wider therapeutic margin than traditional chemotherapy where the margin between safe and sick is often razor thin. Do we need to keep escalating dosages until something bad finally forces a full stop?  Could a dose escalation trial be stopped when we see a strong therapeutic signal, but before we get into trouble?

Remember Paracelsus said the difference between a drug and a poison is the dose.

As I write this, I recognize some possible problems with my suggestion. Which new drugs get treated in this proposed new way and which in the old? How do we tease the groups apart ? My modest proposal still needs some careful noodling by those in the trial design business.

But my bigger issues are clearer.

I talked to a woman today whom I encourage to enroll in a CLL ibrutinib versus ofatumumab trial in Madrid because I believe it to be her best option. I was surprised and dismayed to discover that she would be the first to enroll.


I remain convinced that the shortest and easiest way to get these drugs available to all those who need them is to quickly fill the existing trials and to reach the primary outcomes as soon as possible. Sure, we still need to encourage researchers and pharmaceutical companies to design and open new trials that are as inclusive as possible and that best serve the patients while still getting the necessary data, but those two needs can be in conflict. None of this is simple. We need to start with what we have.

When the data is ready and the time is right, when appropriate, we must support the FDA to broadly approve the new medication and then pressure the insurers to cover it for the full range of indications.

Finally, we need to educate the community oncologists and our fellow patients about the changes that been wrought by the courage of those who jumped into trials and the researchers who supported them.

Painful as it might be, there can be no shortcuts and no diversions to getting these drugs approved. All the i's must be dotted and the t's crossed.

For now, check out clinical trials.gov

Above/Below

And now for something completely different and very calming.

My son-in-law, Nick Sowers, a San Francisco based architect and sound artist creates a surprisingly meditative soundscape.

Enjoy.

JENSEN ARCHITECTS

"Above/Below" is a sound installation which occupies the watery landscape, simultaneously above and below the water surface. Using three pieces of technology to augment my experience--a half-submerged waterproof digital camera, a microphone, and a hydrophone--I listened in on the sounds underwater such as cargo ships all the while tuning in on train horns and various ambient sounds of the Alameda shipping channel. An audio track pans between these two realms seamlessly while the listener stands in front of an image taken by the camera, the surface edge made thicker by the distortion of water on the lens. — at JENSEN ARCHITECTS.

Soon I will publish very informative video interviews with Dr. Tom Kipps from ASH, hopefully more good news when I get my bone marrow biopsy report, and my thoughts on why, despite the great and often urgent human need, it is important to follow all the steps and not rush a trial or the FDA process for drug approval.

But first, dim the lights, move into a quiet room, and take the few minutes necessary to forget your troubles and concerns and instead relax with these simple and beautiful watery ambient sounds.

OSU Update: All Good

I left sunny warm SoCal for cold and snowy Columbus, Ohio, but it was so worth it.

Labs remains stable with essentially normal red blood cells, white blood cells and platelet counts and differential, and boring blood chemistries.  Despite an small audience of student nurses, my bone marrow biopsy went well. It's harder to whine when it hurts if you have aspiring members of the healthcare team staring at your bottom and diligently taking notes. So let me take this opportunity in the privacy of my guest room to say OUCH now.

Results are weeks away.

Dr. Byrd is very happy with my progress, feels the slowed nodal shrinkage noted on my most recent CT scans last month is not a concern in anyway, and I am on a good trajectory.

After my clinic visit and biopsy, I had another interview and photo shoot with their very down to earth and professional marketing team at the James Hospital. This time I am really going to be the poster boy displayed smiling on 8 x 2 feet banners throughout the hospital and possibly at international meetings to promote the hematology and lymphoma clinical trials at OSU. It's a cause that I can fully endorse. As we have heard before, there has never be a better or more important time for a CLL patient to consider a clinical trial and OSU should be high on our list.

This modicum of "fame" allows me to join the ranks of my friend Terry in our local CLL support group who is already the international face and voice of RITUXAN. If this stardom trend continues for our members, our little OC group might need to have its own reality TV show soon.

Insurance issues are on track to be worked out quickly thanks to the hard work and co-ordinated efforts of several folks at OSU and Blue Shield of California today so I am happily leaving town tomorrow informed and consented and officially rolled over into the new continuation trial with a full 84 days of ibrutinib. Yeah. Goodbye Columbus for 12 full weeks.

Hard to believe it's been a year since I first started in this trial, and now that phase of my life has ended.

The next time I am back at OSU at the end of April, spring will be in the air and Dr. Byrd has promised me a much coveted tour of his lab. The marketing team says they may video or shoot photos for my blog- wouldn't that be sweet?

It's been hectic. Despite my nerves about presenting to a "specialists" audience, my lecture on sleep disturbed breathing and heart failure at UCSD last weekend went over well and now I am feverishly preparing my next lecture for the Nation Sleep Foundation in Washington due on Friday.

Life is crazy, but good.

ASH 2012: Dr Jeff Sharman interviewed about the new treatments in CLL

My friend and fellow CLLer, Andrew Schorr did a very nice and interesting interview of Dr. Jeff Sharman at ASH 2012.

Dr. Sharman brings up some new and provocative insights on how the researchers misstepped when searching for a specific genetic target in CLL similar to the famously fused Philadelphia chromosome of CML that Gleevec blocked and in doing so, produced low toxicity, durable remission. This breakthrough drug, this targeted oral therapy, revolutionized not just the management of CML, but the whole approach on how we treat or too often, wish we could treat cancer.

As you have heard many times, in CLL, it is more complicated. In CLL, it all about “turned on” pathways than need a brake applied rather than a specific genetic defect. However, as our knowledge of the activated cellular pathways of the cancerous B cell clone improves, so does our ability to intervene. That brings us to the new generation of small molecules including ibrutinib (PCI-32765), idelalisib (CAL-101 or GS-1101), AVL 292, ABT-199 and others in the pipeline.

He shares his experience of one of of his highly refractory patient finally responding to one of the new trial medications and another where idelalisib worked when ibrutinib failed.

He cautions us that it is way too soon to pick winners among the new molecules.

Some of Dr. Sharma’s tropes you have encountered before from the doctors I spoke with at ASH. It is good to witness the building consensus.

Some of you may know Dr. Sharman from his well-written, informative blog on blood cancers and lymphoma. Check it out if you haven't already. You should also know that he has been a pioneer in small molecule research and an energetic force in developing resources to get clinical trials done.  He talks about their paramount importance right now. He forecasts the end of the world of FCR as we know it. He reflects on how well these drugs work for even those with the worst prognostic markers.

Dr. Sharman asked me if I wanted to share the video. I am, of course, happy to get the word out however I can.

So enjoy and take heart.

Soon I will be posting my ASH interviews with Drs. Furman, Kipps, Wierda, and Wiestner.

On a personal note, I am home from a medical conference in San Francisco, but just for a few hours before I take off again to lecture in San Diego.

My health insurance has me in a ridiculous Catch 22. I can not get pre-authorized for my roll-over clinical trial at OSU that continues my lifeline of ibrutinib until I sign the informed consent, but I can't sign the consent until I am ready to roll-over into the new trial. All but two insurance companies that cover the myriad of patients from far away places that come to OSU for trials understand the fallacy of such a policy and do not insist on the signed consent, but mine is one of the two that makes it difficult.

That said, I am sure it will all work out (retroactively) with the help of some real kind, persistent, and hard working people at both OSU and Blue Shield. Just one more thing to worry about in the meantime.

On Monday I leave for cold Columbus to finish one trial and begin the new continuation trial. While there, I will be busy with a bone marrow biopsy, another photo shoot and interview. Guess which one I am not anticipating with joy. Hint: there there will be no camera or recorder involved, but there will be needles.