ASCO 2014: Dr. Kipps Discusses Targeted Therapy and Obinutuzumab in the Treatment of CLL (chronic lymphocytic leukemia)

In the first brief section of my video interview from ASCO 2014, Dr. Tom Kipps, my personal doctor at UCSD, and mentions the buzz about ibrutinib (IMBRUVICA) at the meeting and then moves on to discuss obinutuzumab (GAZYVA) the new and exciting monoclonal antibody (mAb). He adds to what we learned from Dr. Byrd in this prior post from ASH 2013 and shares his subtly different take on how this powerful new addition to our CLL arsenal works.

My hunch is that it will prove to be much bigger step forward from rituximab (R) than was ofatumumab  (ARZERRA). That much anticipated next generation CD 20 mAb has disappointingly made at best some small incremental improvement for us CLL patients compared to the giant leap that we witnessed just a few years ago when the mother of all CD 20 antibodies, R was added to FC to give us the present "gold standard" of FCR. Ofatumumab does offer a possible helpful option for those of us who can not tolerate R.

Obinutuzumab is clearly proving to be a better antibody. As I covered in this more detailed post and interview from ASH 2013 with Dr. Brown, GAZYA is the first antibody that showed a clear survival advantage over rituximab albeit in combination with chlorambucil.

At ASCO 2014, we learned more. This abstract shows us that as a single agent in untreated patients, obinutuzumab had impressive response rates and even some complete remissions. This almost never happens with the other older CD 20 antibodies. I am pretty excited about all these results.

We already know that adding an antibody to almost any chemo agent makes that chemotherapy work better and explains why chemo-immunotherapy has become the backbone of the present treatment protocols in CLL/SLL and other lymphomas.

What we don't know yet is how this concept of adding a mAb will evolve in the coming era of oral therapies with small molecules such as ibrutinib and idelalisib and later on ABT-199. More on this in future posts.

Here is the first part of my interview with Dr. Kipps.

Listen to the lovely way that he describes how the different type antibodies works.



More to come soon on ROR-1.

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.

ASH 2013: Dr. Byrd on the New Data on Ibrutinib and Obinutuzumab in CLL (chronic lymphocytic leukemia)

In my final post from the last days of ASH 2013 (lots more to come from ASCO 2014), my doctor, Dr. John Byrd out of Ohio State (OSU) in the third part of our interview discusses the durability of the positive results with ibrutinib and the latest results with obinutuzumab. Here is the referenced ibrutinib trial. For the first part of my interview with Dr. Byrd, click here and for part two here. They are worth reviewing as we covered many of the novel up and coming therapies beyond the usual headline grabbers of ibrutinib and obinutuzumab that are the focus of this last segment of the interview.

Dr. Byrd reminds us that it is the usual suspects are the few unlucky ones who do relapse on ibrutinib, mostly those of us who have been heavily pretreated and/or are 17p deleted.

What is the happy surprise is that the side effects seem to get less common the longer we take Imbruvica and there is a hint (see this NIH research by Dr. Farooqui whom I subsequently interviewed at ASCO 2014), that our immunity improves. Certainly the number of infections diminishes over time.

Dr. Byrd also answers my questions on the exciting monoclonal antibody obinutuzumab (Gazyva) and the new study results presented at ASH.

There are many reasons to be excited about this antibody. Despite the fact that the trial was rigged by choosing the wimpy chlorambucil as its sparing partner, Gazyva is the first therapy when used with chlorambucil to show a survival advantage in the difficult to treat mostly elderly patents who have other medical problems (co-morbidities) such as kidney disease that may take many therapies off the table. This trial  is offering hope where there is a pressing need.

We get into some of the details of how the drug is different from other antibodies. Dr. Byrd discusses how its engineering was specifically directed to make it different and probably better than rituximab. We also discuss its potentially nasty and quick infusion reaction and why that may not be such a bad thing.

Enjoy Dr. Byrd.