CLL Society Newsletter with Dr. Byrd on ACP-196 and Dr. Furman answering chronic lymphocytic leukemia questions and much more

The CLL Society’s 2nd newsletter is out at http://www.cllsociety.org/newsletter/.

There is a fresh interview with Dr. Byrd on his exciting ACP-196 data, Dr. Furman answers your questions, Dr. Sharman discussed antibodies, especially Gazyza, I review the basic anatomy of a lymph node in CLL, Terry Evans interviews Sheila Hoff, RN about being a clinical trial nurse, and most importantly fellow CLL patients write about compassion and nutrition and dealing with cancer and a transplant and much more.

Please take a look and let us know if you have any questions or even better if you want to write for us. Any feedback is welcome. 

We did 14 sets of interviews of live interviews with experts on CLL from ASH 2015 so please consider signing up for the alerts ( http://cllsociety.org/newsletter-sign-up/ ) so that you don’t miss any upcoming posting, but as always, all our content does not require your sign in. If you do sign up, we won’t share your data with anyone.

Stay strong.

We are all in this together.

Brian

http://cllsociety.org

HEADING HOME FROM ASH

Our flight is delayed from Orlando and we have a tight connect in Phoenix. What else is new! Not looking good.

ASH 2015 was amazing.  So much good news and clarifying news on novel therapies.

Watch here and on the CLL Society website for the news, interviews and updates.

Here are a few teasers:

• Venetoclax (ABT-199) looks very helpful for those who have failed ibrutinib or idelalisib.
• ACP-196, a new BTK  inhibitor has stellar results with few side effects.
• Ibrutinib does a super job upfront in the over 65 gang. Should become standard of care frontline.
• The addition of idelalisib to bendamustine and rituximab (BR) greatly improves outcomes, but the use of idelalisib frontline needs to be managed more carefully to get the good results it offers due to increased risk of liver issues.
• Promising results with new signal blockers such as ONO-4059 and duvelisib and TG-1202 and the immune modulator, CC-122 and high dose methylprednisolone (HDMP) and new antibodies and much more.

More details and other results soon.

Stay strong.

Gotta get ready for our flight, I hope. The problem is a broken bathroom door.

UPDATE: After changing the flight 3 times, we would have missed our connection by about 15 minutes, so we changed everything to fly into LAX  more than an hour from home, but at least in the same time zone. Our bags are a different story.

Brian

I am off to ASH 2015 to learn everything I can about CLL and I have a miserable cold.

I got my biannual cold that seems to come just as I am planning to get on the plane to the be the only family doctor among 30,000 or so hematologists and researchers from around the world.

Despite my aches and cough and runny nose, I am looking forward to learning all that I can on CLL, absorbing it and sharing it here and on the CLL Society website.

Highlights include the first data on an ew BTK inhibitor, ACP-196 (NEWS BREAK: now officially called acalabrutinib), more on other exciting drugs in development including venetoclax (ABT-199) and several promising new signal blockers and more on SYK inhibitors and new antibodies and new combos and more on approved drugs such as ibrutinib and idelalisib and obinutuzumab and ofatumumab and more smartly focused material on chemo and on new understandings of how CLL is treated in the real world and how it might be treated soon and so much more.

Plenty of interviews scheduled with experts from around the world, many whom are old friends and some who are new to me, but have published important research.

Hundreds of great abstracts (I have reviewed about 200 so far) and many oral presentations and press conferences.

I am also meeting with other patient advocates and friends from around the world to share best practices.

I will try to share some live updates from ASH 2015 because it is so exciting, but mostly I like to digest the research over a few weeks so that it can be understood and put in meaningful perspective.

The only thing missing is lots of sleep.

So now I am going to bed. Flight tomorrow AM.

The Kindness of Strangers: Getting my IVIG to Control my CLL (chronic lymphocytic leukemia) induced ITP

" I have always depended on the kindness of strangers."

Blanche DuBois from A Streetcar Named Desire

As did Blanche,  I too have depended on the kindness of strangers.

For the last nine years, every few weeks I show up at the cancer infusion center to sit for hours to receive intravenous immune globulin or IVIG. Recently I have stretched the interval between IVs to 7 weeks. 

By mechanisms that are not fully understood, it blocks my stupid auto-immune antibodies from attacking my own platelets that in the past has lead to multiple hospitalizations and fearful encounters with my own mortality when my platelet counts crashed and I was at risk for major bleeds. Thankfully, that is all behind me now.

I  have gradually and cautiously been able to taper off all the other meds for my ITP (immune thrombocytopenia) and my platelets have not fallen. 

Perhaps my ibrutinib helps turn off my auto-immune triggers. As seen in this recent post there is good reason to be hopeful. There are case reports of ACP-196, another promising BTK inhibitor helping too.

Perhaps I no longer need the IVIG, but I am not brave enough to stop it to find out. ITP is scary.

There is another reason not to quit.

My infusion 7 or 8 x year may also protect me from all sorts of infections. And that is important in my work as a doctor and in my fun as a grandfather where I exposed to lots of germs.

Due to the recent measles scare, all the doctors at the hospital where I work were ordered to have blood work to confirm their immunity. I objected for several reasons:

1. I had had measles as a child
2. Due to my CLL, I couldn't take the live vaccine even if my test came back negative.
3. My antibody levels are not my own.

This last one is because of the IVIG that I receive. It is a pooled blood product from 1000s of strangers and by definition contains their antibodies against everything they have either had or been vaccinated against.

No wonder I was immune to everything that I was tested for.

But am I really?

Truth is that it's not me. It is the kindness of strangers' blood that is protecting me. It is known as "passive" immunity as I played no role in forming the antibodies. When the IVIG disappears as measured by the IGG level in my blood dropping after a few weeks as it must, my immunity fades too. IVIG does not boost IGA or IGM, two other important antibody classes, only IGG. 

Compare this to a vaccination where we attempt to mount an "active" immune response that is remembered and always ready to respond. Sadly in CLL, this is usually a barren effort. Flu shots and  other immunizations don't usually work well for us. And we must never risk getting a live vaccine as it might run amok in our bodies due to out immune-incompetence. We are notoriously lousy at making healthy antibodies.

So while I take my IVIG to protect my platelets, it is clearly helping me in other ways.

Thank you kind strangers. Your generous gift of your own blood has touched so many lives that you will never know.

Last chance for the CLL (chronic lymphocytic leukemia) Survey and the News About the Agreement between Gilead and Ono

We are taking down the survey at midnight tonight Pacific Time, so if you haven't completed it, please let us know what will be important to you in a CLL website and support groups.

Here is the link to the survey: https://cllsociety.questionpro.com

And thanks so much to the over 400 of you that completed the survey and the many who have made a donation to the CLL Society Inc. to jumpstart our process.

                                  


Finally I want to share this press release from Gilead:

ONO  AND  GILEAD  ANNOUNCE  EXCLUSIVE  LICENSE  AGREEMENT  TO  DEVELOP  BTK  INHIBITOR,  ONO-4059,  FOR  THE  TREATMENT  OF

B-CELL  MALIGNANCIES  AND  OTHER  DISEASES

-- Companies will Collaborate Jointly on Global Development of ONO-4059 --

Osaka, Japan, and Foster City, CA, December 18, 2014 - ONO PHARMACEUTICAL CO., LTD. (“ONO”) and Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the companies have entered into an exclusive license agreement for the development and commercialization of ONO-4059, ONO’s oral Bruton’s tyrosine kinase (BTK) inhibitor for the treatment of B-cell malignancies and other diseases.  Under the terms of the agreement, Gilead will pay ONO an upfront payment plus additional payments based upon achievement of certain development, regulatory and commercial milestones.  The companies will collaborate jointly on global development of ONO-4059.  Gilead will have exclusive rights to develop and commercialize ONO-4059 in all countries of the world outside of Japan, South Korea, Taiwan, China and the Association of Southeast Asian Nations (ASEAN) countries, where ONO retains development and commercialization rights.  

ONO-4059 is a selective, once-daily, oral inhibitor of BTK, which has been shown to play a role in the survival and proliferation of malignant B-cells.  ONO has presented preliminary Phase 1 data showing clinical activity in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) at several scientific conferences.  ONO and Gilead plan to develop ONO-4059 for the treatment of B-cell malignancies and other diseases as a monotherapy and in combination with approved and investigational agents, including combinations with kinase inhibitors in Gilead’s portfolio. 

“We are pleased to partner with Gilead to accelerate worldwide development and commercialization of ONO-4059,” said Gyo Sagara, ONO’s President, Representative Director and Chief Executive Officer.  “Our goal is to bring better therapeutic options as quickly as possible for the patients with B-cell malignancies or other diseases in the world, and we believe we can fulfill the goal by pursuing the development of ONO-4059 with Gilead.”

“With this agreement, Gilead now has compounds targeting four unique signaling pathways associated with B-cell malignancies – PI3K delta, Syk, JAK and BTK,” said Norbert W. Bischofberger, PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer.  “In addition to evaluating ONO-4059 in combination with standards of care, we believe there is an opportunity to combine this compound with Gilead’s other kinase inhibitors with a goal of achieving more pronounced and more durable response rates.  We look forward to working with ONO to move the ONO-4059 development program forward as quickly as possible.”

About ONO PHARMACEUTICAL

ONO PHARMACEUTICAL, headquartered in Osaka, Japan, is an R&D-oriented pharmaceutical company committed to creating innovative medicines in specific areas. It focuses especially on the diabetes and oncology areas.  For more information, please visit the company’s website at http://www.ono.co.jp/eng/index.html.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need.  The company’s mission is to advance the care of patients suffering from life-threatening diseases.  Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Gilead Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including risks that the parties will be unable to develop and commercialize ONO-4059, as a potential monotherapy and in combination with other therapies, for the treatment of B-cell malignancies or other diseases.  These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements.  The reader is cautioned not to rely on these forward-looking statements.  These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2014, as filed with the U.S. Securities and Exchange Commission.  All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

###

This is good news as we need more options and Gilead is a smart company that has a strong track record on getting new and important drugs approved. It also has other small molecules including idelalisib that might make sense in combination therapies. The market seems to approve of the move as this joint effort should increase the likelihood we will be seeing ONO-4059 become commercially available.

Ibrutinib is a great BTK inhibitor and has set the bar very very high in terms of its response rates and tolerability, but still it won't be the right choice for all patients due to some intolerance or adverse outcomes or lack of efficacy, so having another Bruton Tyrosine Kinase inhibitor option is something all patients should want.

And waiting in the sidelines is Acerta's ACP-196- no data to report yet, but the buzz about this new BTK inhibitor is very promising.

Abbvie, Janssen, Pharmacyclics and others are looking at new non-chemo combos in trials in the hope of going from control to cure. More on these trials and plans soon.

2014 was a great year for those with CLL. 2015 may be even better.

Happy Holidays to all.

ASCO 2014: Dr. Furman Gives us Perspective on Resistance with Ibrutinib in CLL (chronic lymphocytic leukemia)

More of My Son, Ben's Mural Work

ASCO 2014 was only a few months ago, but happily the CLL world is a fast moving place.

Since this video interview with Dr. Rick Furman of Weill Cornell, recorded and edited by Andrew Schorr and his team at Patient Power, idelasilib has been approved for CLL (see this post for discussion of its labeled indication) as predicted by Dr. Furman, and ibrutinib was approved for frontline therapy in 17p deleted patients (see this post).

YEAH to both!

Also in the intervening months, new mathematical models that consider evolution of resistant sub clones have been published by Dr. Burger out of MDACC and a high powered mathematical team headed by Dr. Natalia Komorova out of UCI. (I plan to interview Dr. Komorova as we are practically neighbors in Orange County, CA). Similar research, but this time using deep genetic analysis of the cancer's evolution over time by Dr. Cathy Wu from Dana Farber was presented at AACR 2014 Hematologic Malignancies Conference last week. (I also plan to post on her important research soon.)

The issue of ibrutinib resistance may be becoming an increasingly important issue. More and more of us are doing great with our BTK inhibited, but we still have residual disease and if you are similar to me with bad markers such as clonal diversity, 17p deletion, 11q deletion, and have a history of having been heavily pretreated (I have the first three for sure and many would say the 4th with my bone marrow transplant), then the fear of a resistant sub clone starting to act out, while still not the case for most of us even with the worst of the worst disease, is based on a growing reality of a droopy Kaplan-Meier (KM) Curve. Below are KM plots from OSU published in NATURE at the start of the year that show the downward drift in progression free and overall survival for those of us that are 17p deleted. As you can see the curves are way better than anything else out there, but they are hardly perfect.

This whole resistance issue might be largely obviated in the future by moving the new therapies up to frontline status. Dr. Furman and I both agree that is the direction we need to encourage with appropriate trials and struggles with insurers to pay for these drugs in all treatment naive patients.

Dr. Furman also mentions two exciting new BTK inhibitors, ACP-196 and ONO-4059. Click on the drugs' names to be linked to their phase 1 trials. We are just in the first chapters, but it is looking that the stories they will tell should have very happy endings. Please consider trials that offer these drugs among your treatment options.

Here is my ASCO 2014 interview with Dr. Rick Furman.



As there is a small but significant cohort of FCR patients that do great for years and years, there is a much much larger cohort of patients taking ibrutinib and other small molecules, now based on more than on more than four years of data, that should continue to do well year after year.

I am so happy for all these patients.

But I worry about the minority who won't do well, who will relapse. I am not giving up on my plea: Don't leave us stranded on 3rd base- Get us to the home plate of a cure with a follow up therapy.

We discuss obinutuzumab and ABT-199 as mop up therapies and I think those are smart choices. Maybe it will be cirmtuzumab, a new ROR1 mAB discussed in my recent post with Dr. Kipps from the very same meeting. We will only find out with clinical trials.