Dr. Tam on Venetoclax (ABT-199) for treating CLL (chronic lymphocytic leukemia)

Friends,

This week in the Conference Coverage section of the CLL Society website, we have posted an interview from the 2015 iwCLL meeting with Dr. Constantine Tam. We talked about Venetoclax (formerly ABT-199), the early experiences and the results that are being achieved now. It's very informative and worth watching all the way to the end. You can see that interview here.

I have posted about quite a few CLL educational meetings that have been organized by other associations in 2016 and will be posting about more as we become aware of them. We will travel to as many as possible to both create awareness of the CLL Society and our resources, but also to help organize patient/caregiver support groups where there is interest. Many of you have shared with us your locations and your interest in having a support group in your area. Know that we have captured that information and will post new information as it becomes available. The CLL Society will also be planning a few patient/caregiver educational meetings this year and we will keep you updated.

In the meantime:

CLL Meeting in Miami, FL: For those of you in the Miami area, there is a CLL patient meeting hosted by the Florida Society of Clinical Oncology (FLASCO) being held on February 24th at the Miami Marriott Dadeland at 5:00 PM. A complimentary buffet dinner will be provided. I'm not able to attend this meeting, but you'll have the opportunity to ask questions of the expert speakers. Register and find out more information here.

CLL Meeting in Atlanta, GA: For those of you in the Atlanta area, we just became aware of another patient meeting in February: Saturday, February 27th in Atlanta starting at 9:30 AM at the Sheraton Suites Galleria-Atlanta (View Atlanta flyer). CLL patients will be sharing their personal stories, and a local CLL expert will be providing a talk on the basics of CLL. You can call 844-482-6815 to register. A complimentary meal and parking will be provided and you are welcome to bring a guest. I will be at the meeting with an exhibit table and will stay afterwards to meet with attendees to discuss the resources available from the CLL Society. I look forward to meeting you there.

Stay strong.

We are all in this together

Brian Koffman

Volunteer Medical Director of the CLL Society

http://cllsociety.org

http://bkoffman.blogspot.com

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.

Bad knees, Baker's Cysts, and Good Times with CLL (Chronic lymphocytic leukemia), plus our newsletter

I tripped walking into my medical office yesterday, scraping the front on my left knee just below the patella. I was tired, jet lagged having arrived home from Hobart, Australia less then 2 days earlier, was carrying a lot of stuff and was distracted talking on the phone with someone with CLL facing some tough choices. But I don't need any excuses. I fell because I have a bad knee. Actually two bad knees. Two very bad knees getting worse.

Happily my knees are slow to react to trauma. I was able to hobble through a busy day of patients, but by the end of the day I knew I was in trouble.

When I stress my knee (this is the second traumatic strain of my left knee in less than a month), there is no forgiveness, no flexibility, no resilience. There is only pain and swelling and loss of function.

In this case despite the anterior trauma, the back of my knee swelled up with a huge but benign Baker's cyst, a synovial swelling that restricts my ability to fully extend my joint and thus to walk without pain and a forward leaning posture reminiscent of the elderly osteoporotic women I met in my travels to Japan.

The good news is that it little hurts as long as I lie still with it raised, slightly flexed and packed in ice.

Which is what I did today. All day.

There is no definitive treatment for a Baker's cyst. The real treatment is to take care of the problem causing it, namely in my case, the end stage osteoarthritis of the knees. Blame street hockey or junior high football or my mother's arthritis.

My joints spaces are so narrowed medially that I have lost height due to a varus or bowlegged deformity that makes me look as if I have rounding up cattle all my life.

After a total of four surgeries, the only answer left on the (operating) table is to totally replace the knees.

I have scheduled the surgery twice now and backed off both times.

Why? Because if I vigorously exercise to stretch and strengthen my knees it partially ameliorates the pain. I am pretty good at that a home, but lousy when I am the road as I have been for 15 days in Australia.

If I use my walking sticks and acetaminophen and ice as I just did in Australia for two weeks, I can muddle through and still accomplish many miles of painful but manageable walking.

Until I fall or twist or the knees just give out on their own. And that's happening more these days.

So why have I cancelled the surgery twice now?

Due the increased bleeding risk with ibrutinib, by protocol I would have to be off my ibrutinib for one week before and three weeks after while I am on blood thinners post-op from my bilateral knee surgeries used to prevent blood clots. I have chosen to be part of the 15% or so brave or stupid patients that do both at once to get it over with and limit my time off my cancer therapy.

Here are the issues I would face:

1. Being off ibrutinib for more than 8 days almost triples (13% versus 31%) my risk of relapse. I'd be off for about a month. Here is the recent ASCO abstract that lays out the facts. 
2. Joint replacement surgery itself may be associated with an increased risk of blood cancers.  Makes sense when they are shoving titanium and glues up your hollowed out bone marrow. Reading this article will give you pause before you let an arthropod take a saw to your bones. 
3. I am at higher risk for peri-operative complications due my CLL including infections, bleeding and clots.
4. I have never lost a patient yet to osteoarthritis, but some patients who have relapsed from ibrutinib have had a poor prognosis. Here's the article from JAMA Oncology. 

Now if you dig into the studies that I am referencing, you learn quickly that the patients who went off ibrutinib for more that 8 days were generally much sicker and quite different than me and that whole study is being questioned, the total joint patients with subsequent blood cancer are still rare and a broad mix of surgeries, and the relapses post ibrutinib were clearly a different group than me.

It is important when you review any research that you critically assess if you belong to the group being studied. Except for the study on joint replacements (and even that is questionable), I don't belong to any of the study groups.

Still, as long as I can walk, I am staying away from the scalpel.

And odds are that I will be walking much better by tomorrow. The ice and rest has helped a great deal.

But there is another better option if time and circumstances allow. And they should.

We all know that as good as ibrutinib is, it is not a cure. Trials of dual and triple therapies are already opening in response to this unmet need, but I would only qualify today if I fail my ibrutinib.

I am pushing for trials that add in venetoclax (ABT-199) or a PD-1 inhibitor for that growing cohort of patients such as me who are doing well on ibrutinib or idelalasib, but who still have residual CLL. Don't wait for it to take off. Hit it while it's down by adding a second agent.

In my case under the cover of a second anti-CLL drug that doesn't effect bleeding, I would then replace my damaged knees and have control over my two biggest health issues, my cancer and my arthritis.

That's my plan and I am pushing hard to make it happen. These are good times for those of us with CLL and are options are getting better and better.

UPDATE: Knee still swollen with limited flexion on day three. Walking is not happening despite a night of elevation and ice. 80% better by day 7.

On a less personal note, the CLL Society was very busy in Australia with iwCLL 2015 being the only CLL group reporting from there, so stay tuned for some updates. Yours truly spoke in front of several hundred doctors on a panel with Dr. Michael Keating and other giants in CLL. Very humbling and very honored to have shared the patient's perspective in Sydney.

I'll be in Brooklyn Oct. 3-4 for LRF's 20th Annual North American Educational Forum on Lymphoma and would love to say hello. Drop me an email and we can try to connect.

Big news:

The CLL Society's inaugural newsletter is coming out later this month. It promises to be amazing with some wonderful articles written by fellow patients and caregivers and with some great surprises. If you haven't already, please sign up for it here. We won't share your info with anyone and you will be sure to be aware of all the upcoming posting from iwCLL and ASH and much much more. The newsletter will be quite different from this blog or  our CLL Society website, so please sign up here and don't miss it.

And if you are in the Seattle area, consider this meeting with John Pagel and a CLL patient and caregiver:

ADH 2014: Dr. Sharman on Cell Death in CLL (chronic lymphocytic leukemia), a patient meeting, a newsletter and iwCLL

Friends,

This week on the CLL Society website, in our Conference coverage section, we share the second part of an interview from ASH 2014 with Dr. Jeff Sharman with a discussion of the life and death pressures on our B cells and how that relates to ABT-199. We also cover the latest research on idelalisib and rituximab, and what research in general is still needed.

I'm heading off to the International Workshop on CLL in Sydney, Australia today and will be attending sessions and doing interviews while I'm there. I'll be posting new information upon my return. Stay tuned. We are also co-sponsoring a small patient meeting with Lymphoma Australia.

Also, we will be sending out our inaugural newsletter, the CLL Tribune at the end of September. Don't miss this special collection of research news, basic CLL information, fun facts and a wealth of wisdom and shared experiences from our fellow patients. If you are receiving this information through a CLL Society Alert email, you are already signed up to receive it. If you are reading this through another source, sign up to receive it here.

For those of you in the Seattle area, we just became aware of a patient meeting that will be held on Saturday, September 26, 2015 starting at 9:30 AM at the Sheraton Seattle Hotel. Two CLL patients will be sharing their personal stories, and Dr. John Pagel from the Swedish Hospital will be providing a talk on the basics of CLL. You can call 844-482-6815 to register. Complimentary breakfast and parking are provided and you are welcome to bring a guest. You can view the flyer for the event here.
Stay strong.

We are all this together

Brian Koffman

Volunteer Medical Director of the CLL Society

http://cllsociety.org
http://bkoffman.blogspot.com

ESH 2014: The Future Role of FCR and new data on venetoclax and rituximab in CLL (chronic lymphocytic leukemia) and my latest lab results

I thought I sneak in one last post from LAX before I board my plane to Wroclaw, Poland via Munich.

It is mostly about the new posts on the CLL Society's website and our nonprofit's news, but I wanted to share that my latest lab results from my visit to the infusion center for IVIG remains most boring with a low normal hemoglobin, a high normal platelet count and an absolute lymphocyte count of 1.2.  YEAH! Of course that really matters is the count of clonal B cells and that takes flow cytometry, but at least I know that nothing major is happening. Slow and steady makes me happy.

This week on the CLL Society website we bring the second part of our interview with Professor Michael Hallek of Koln, Germany, the director of the German CLL Study Group and a major CLL researcher and thinker.

He starts by discussing his “fast boat” adaptive trial strategy (similar in many ways to that of Prof. Hillmen in the UK), essentially looking for the most tailored therapy based on not just predictive factors, but also on how we patients actually respond in trials. He is looking for what I call that perfect Goldilocks’ mix of “ as much as necessary, as little as possible” therapy.

In the second half of the interview, he makes a cogent argument for the ongoing use of FCR frontline in select patients. While many of us are not fans of chemo-immunotherapy (CIT), Professor Hallek has strong data to support his perspective. Listen with an open mind.

Please give a look here in our section on conference coverage from 2014.

We also share my comments and background on an important oral abstract presented at the 20^th Congress of the European Hematology Association (EHA), June 11-15, 2015 on venetoclax (ABT-199 or GDC-199) and rituximab. In relapsed patients, the total response rate, the complete response rate, the MRD- rate and the ability for some to be able to remain disease free after stopping the drug is important data that you can find here in our 2015 conference coverage section.

We have a significant backlog of important educational material mostly from large conferences such as ASH 2014 and others from 2015 that we plan to post over the next few months.

In a first step to speed up the process, our first high school intern volunteer, the granddaughter of the CLL Society's attorney, has joined us online to help her earn her community service hours by helping us catalog all the videos that we have produced and are storing on the web.

We are working hard to expand what we offer to the tens of thousands of online readers and to actuate our ambitious plans for patient-centric, physician-curated live education and support. One volunteer medical director (yours truly), his unpaid wife and one part-time RN can’t do it all, although I have to say we have made some amazing progress in our mission to meet the unmet needs of the CLL community in the less than 90 days since our nonprofit’s website launched. Our website is #1 in organic Google searches for CLL Society despite having no search engine optimization in place. We are too busy trying to get our content up.

There is so much more we must do. Your suggestions, help, support, donations, ideas, and feedback are what guide us and keep us going.

We remain forever committed to open content for all with no need to sign in or share any of your personal information to see a video or to get the help you need. If you haven’t done so already, we encourage you to please sign up to receive alerts regarding new postings and for our quarterly newsletters (first one will be published in September) and to share with other patients, caregivers or concerned family or anyone whose life is touched by CLL.

The CLL Society will be at iwCLL in Australia in September to cover the news and we are planning an amazing patient meeting the day before the researchers' meeting in Sydney with Lymphoma Australia. 

Stay strong.

We are all in this together.

Brian Koffman

Volunteer Medical Director, CLL Society

Dr. Wiestner on Novel Therapies for CLL (chronic lymphocytic leukemia), Oral versus IV therapies, Idelalisib plus Chemo-immunotherapy Update and my Lingering Cold

Our very thin CLL Society team is busy preparing for the ASCO (American Society of Clinical Oncology) 2015 Annual meeting which starts at the end of this week in Chicago, but we still found time to bring three diverse and instructive new topics to our website http://cllsociety.org for this week.

Today, Monday, May 25, 2015, we posted Dr. Adrian Wiestner's thoughtful and well-considered interview from ASH (American Society of Hematology) 2014 on what is known and unknown about novel therapies. You can find that here.

Expect more video interviews and commentaries from ASH 2014 over the next several weeks.

On Wednesday, the camera is turned on yours truly for my personal take on CLL topics of interest. We include the short video and an updated transcript on this week's topic of oral versus IV medications. I think you might be surprised at some of the issues and non-issues in what would seem at first glance to be should be a simple choice. I have posted extensively about the tragedies that were associated with potent oral medications before we knew about the risk of tumor lysis with ABT-199 now known as venetoclax or in the case of lenalidomide (Revlimid), where there is also the risk of tumor flare. These risks have largely been mitigated now with new dosing protocols. Please see this prior blog post for part of the story.

 This new section on the CLL Society website using monologues and text will roll out here.

And this will be only the first in a long series of instructional postings on the various CLL therapies.

On Friday, we will post an up to the minute review of and link to an important ASCO 2105 abstract about the latest data on combining idelalisib with chemo-immunotherapy. You will find it here on Friday.

Please let us know what you think, especially about my reading and the transcripts of my monologues. You can contact the CLL Society here or email directly, but the 1^st method is preferable.

We are constantly working to respond to the unmet needs of the CLL community, so we listen carefully to what you write us and try to respond as best we can.

We don't have a big production budget and team or large institutional backing, but we keep going to offer up the most robust and recent, yet still accessible information with no gloss and no agenda other than to inform our community.

Because we believe that SMART PATIENTS GET SMART CARE™

Switching to a personal update, my wife and I are stilling struggling with a lingering upper respiratory infection aka a cold that my beautiful granddaughter shared when visiting from Chicago. No fever or cough for me. With the frequent use of a Neti pot, normal saline and steroid nasal sprays and a single shot of a decongestant (and no antibiotics), I have managed to control the symptoms and survive the pressure changes in the first of several air flights.  Both of us remain “under the weather” after a full week of symptoms, but we are slowly improving.

For most of my immune-competent patients, I would never recommend an antibiotic in such circumstances, but I am not most patients and either are any of my fellow CLLers. We are all immune comprised. Our immune systems are as dysfunctional as hyperactive adolescents who are asked to focus on a single boring multi-step math problem while the rest of the vibrant world pours on around them. Like those teenagers, my immunity’s focus is weak and easily diverted to the wrong target, having lead in the past to my nasty autoimmune problem of ITP.

Tomorrow I am at Ohio State for my three-month follow up on my ibrutinib trial.

Expecting another good lab report. Usually my neutrophils jump up when I am sick at all, even with a viral illness.

I wonder if Dr. Byrd will add an antibiotic and chide me for treating myself, always an ill-advised choice.

Personal confession: I worry about my admittedly relatively mild added illness. Worrying is already too easy to do with CLL, and even more so when we are sick. URIs can lead to chest infections and pneumonia is still the leading cause of mortality in CLL.

I will be much happier when this infection is gone.

I will be home one day this week, long enough to get my every 6 week dose of IVIG.

Late in the week, I will be Orlando for less than 24 hours to lecture on anemia and gout to some 400 primary care providers. Then I fly onto Chicago for the very busy ASCO (American Society of Clinical Oncology) Annual meeting.

Rest is not in the picture. But it is a good busy and I will be with friends everywhere I travel.

I may even get to see the little girl who gave me the cold in Chicago. If we are both well.

Thanks

Stay strong

We are all in this together.

Brian Koffman

Volunteer Medical Director of the CLL Society

ASH 2014: Interview with Dr. Susan O'Brien and Dr. Bruce Cheson on CLL (chronic lymphocytic leukemia)

There is much to report from ASH 2014, and this sweet interview from Medscape offers a short synopsis of some of the highlights.

Over the coming weeks I plan to fill in the details with more comments and videos, but this is a nice and succinct place to start.

There are some priceless moments, thanks to the wise and dry humor of Dr. Cheson and the honest and patient centric attitude of Dr. O'Brien.

First, right up front, I really appreciate that Dr. Cheson points out just how out of date are even the most recent CLL guidelines that were developed only a few years ago.

Are you listening, community oncologists? The published CLL guidelines are out of date.

I am glad he also asked about the secondary malignancies with chemo-immunotherapy, a question too often swept under the carpet in many presentation on CLL treatment. We know there is a small but real risk of MDS or myelodysplastic syndrome (for an explanation of the relationship of MDS and CLL from Dr. Steensma, click here), a difficult to treat form of cancer that presents as bone marrow failure, that may come along as a late and serious complication with FCR (fludarabine, cyclophosphamide, and rituximab), but we don't have much data yet on the risk with BR (bendamustine and rituximab).  Because bendamustine is a DNA damaging alkylating agent similar to chlorambucil (Leukeran) and cyclophosphamide (the C in FCR), it is likely that MDS will also present as a late, but hopefully infrequent ugly complication after BR.

What we do know already is that now that we are living longer with our CLL, we are getting more secondary cancers (click here for a reminder of our risks), especially blood cancers.

Don't miss Dr. Cheson's hand gesture when Dr. O'Brien talks about the minority of patients that do so very well on FCR, a topic that we have visited here more than once (click here to hear Dr. Hallek at  iwCLL discuss who gets the most benefit from FCR).

Another highlight comes right after the honest discussion of the follow up important trial of the two old school chemo-immunotherapies that are duking it out for supremacy in the CLL world, namely the  FCR versus BR (for more on this trial from Dr. Sharman click here). After Dr. O'Brien's honest and upbeat response, Dr. Cheson asks her, quite properly in this era of new treatment options: Do we care?

Yet another interesting moment occurs when he asks Dr. O'Brien to choose between ibrutinib, idelalisib, and ABT-199: If they were all available: Which one would you pick?

She refuses to answer.

Their discussion on the meaning of minimal residual disease or MRD negativity in the era of novel therapies is both informative about what we know but even more so about what we don't know.

Only time and trials will help sort al this out.

Dr. O'Brien has her own hand gesture when she describes just how much above 50% was the progression free survival curve for ABT-199 at 18 months. We need more data. And more time to sort this all out.

I wish I had produced this video. I don't usually see the role of my blog to share what is already available on other websites, but this is good stuff and there was much in it that cried out for commentary and context. I wanted everyone who reads my blog to have the link with it here.

Please enjoy this Medscape Interview:

CLL: It's the Best -- and Most Confusing -- of Times

Thanks for your help and support.

                                          

ASCO 2014: Dr. Farooqui on Trials at the NIH, ABT-199, and Issues of Long Term Oral Therapies in Chronic Lymphocytic Leukemia (CLL)

In my last video interview from ASCO 2014 (several audio only interviews to come), with help from my friends at Patient Power, I interviewed Dr. Mohammed Farooqui from the NIH on the research and trials ongoing at the NIH, his enthusiasm about ABT-199 and the questions he and others are researching on longterm use of the novel oral meds.

Do keep in mind that all trials at the NIH in Bethesda are all free, with or without insurance. They even help with your airfare and hotel, and they are open to any one in or out of the USA.

The natural history trial on CLL is still actively recruiting and deserves our support. The care one will get at the NIH will be world class. A win-win situation.



It is not surprising to hear the honest response about getting adequate accrual in a chemo-immunotherapy trial is more difficult these days. I have heard similar concerns from other researchers. Now that ibrutinib and idelalisib are approved and available outside of trials, many of us are no longer considering clinical trials, especially where there is a computer randomly deciding whether we get the drug of our choice. Even trials offering an option of free ibrutinib and idelalisib are enrolling more slowly.

Dr. Farooqui also shares my excitement about ABT-199. Complete responses (CR), let alone minimal residual disease (MRD) negative responses, are rare with the two approved (though that may be changing as Dr Burger has some research showing CR and MRD negative responses with ibrutinib and mAb therapy- more on this important data point later), but CR and MRD- do occur in combination trials with ABT-199. 

I keep trying to get an answer to my question that is so pertinent for me and many others: what does it mean to walk around with residual disease (or not). There is still no answer and it will only be revealed with more time and more research. Dr. Farooqui does nicely lay out the possibilities.

Soon I will be posting some great audio only interviews from ASCO 2014 with Drs. O'Brien, Byrd, and Sharman. Next month I will be reporting from both ASH 2014 and early next week from the International Conference on New Concepts in B Cell Malignancies: From molecular pathogenesis to personalized treatment but this is your last chance to see me with a goatee on camera.

I have not been home for more than a few days at a time in over a month. After next week, I will have been at six medical conference, in two continents, in 6 different cities, lecturing on five different topics from alternative medicine to gout to CLL. ASH in San Francisco, a short vacation in Yosemite and maybe a quick turn-around trip to London to speak on CLL are on tap before the years' end.

This crazy schedule needs to stop.

And it will.

My plan and commitment to you is that in the very near future my focus will narrow from teaching about a variety of medical topics to only focusing on my passion to spread the news about CLL and related B cell lymphomas. I have big plans and I will need your help and support to make them come true. More to follow soon.  (There is a hint of the exciting news to come in the interview).