Off to iwCLL 2015 to learn, teach, share, support and report on CLL ( chronic lymphocytic leukemia)

Friends

I am off to Sydney, Australia tomorrow with our nonprofit CLL Society where I will be your unpaid in person reporter from the meeting.

I am also speaking at iwCLL 2015 on a panel with Dr. Michael Keating, Dr. Andrew Roberts, and others on the Funding Equation where we will discuss ways to improve access to our meds despite their expense. I am talking about the Canadian and American patient experience.

And despite greatly discouraging logistical difficulties, we have also organized a patient Q+A session in conjunction with the wonderful team at Lymphoma Australia in Sydney for patients that are coming from as far away as New Zealand. We should have video from the doctors attending: Drs. Wierda, Wiestner, and Trotman.

It’s a very very long trip, and much work, but I am excited about this amazing opportunity to go and to share what I learn firsthand with the gang here.

Let me know if you have any burning questions for the gathered experts.

Stay strong.

We are all in this together.

Brian

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

ASH 2012: Dr. Richard Furman Discusses What is Known and What Isn't About the New Treatments in Trials

In the final part of Dr. Furman's interview from ASH 2012, the doctor who had the most early experience with GS-1101 (idelasilib) and ibrutinib discusses the still limited experience of disease progression with these new small molecules. He reminds of the real risks of bone marrow damage (MDS) and transformation to a more aggressive cancer (Richter's) and offers an interesting hypothesis on why Richter's might be found more often with these treatments.

He reviews the open pivotal for idelasilb (GS1101) and the associated crossovers, plus the trial for ibrutinib versus ofatumumab.

But there are other trials out there too that he didn't mention, especially for patients in special categories, such as 17p deletion or age  > 65.

So always remember to check what clinical trials might be a fit for you at http://clinicaltrials.gov when you are considering treatment. Don't count on your doctor to know all the latest. See my prior post on clinical trials.

Dr. Furman candidly outlines what is known and not known about how these drugs work.

What I really like is the strategy he outlines of using these drugs one after another as stepping stones to a normal life expectancy.



More to come from ASH 2012.

ASH 2012: Dr. John Byrd and the Dream of Magic Bullets: The History and Science behind the Success of the BCR blockers such as Ibrubinib (PCI-32765) and Idelalisib (GS-1101 or CAL101)

In the first of a four segments of my interview with my own wonderful doctor at OSU, Dr. John Byrd, we hear him discuss every patient's dream of a magic bullet and how the history and science of TKIs in general and BCR blockers in particular lead us tantalizingly close to that magic moment.

Be prepared to hear a progression free survival rate in the trial that Dr. Byrd presented at the ASH press conference that will knock your socks off.

Be prepared for some surprisingly good news on what happens to the adverse events the longer you are on the medication.

If you have visited my site at all in the last few months, you are already prepared for the news of the changing of the guard from old school cytotoxic, collaterally damaging, mutagenic chemotherapy to the emerging gentler targeted biological approaches.

 Dr John Byrd ASH 2012

My wife and I leave for Ireland next week, but I hope to continue to post more of the interview every few days. Even ancient castles have the internet these days, but expect shorter commentaries.

The house, the vegetable garden, the tea trees, and most importantly, the cat will be cared for by my adult children who will be moving in during our absence.

Packing the clothes is the easiest part of getting ready. Many layers, and be prepared for the cold and wet.

I have burned about 4 hours of traditional Irish music to keep as going as we drive from village to village in our little rental car.

Paperwork and boarding passes may be an issue as United Airlines and Aer Lingus don't seem to like to play well together. I am hoping our status with Global Entry and TSA-Prescreen will help, but I am not counting on it. The connection in Chicago is tight.

The real work is getting all my precious meds organized for my daily needs. That takes hours of counting out pills. The idea of schlepping more than 20 bottles of my daily and my just in case medication is overwhelming. Without my meds, I would be in trouble fast, so I always bring extras for a few days' buffer. And I bring emergency meds for sudden infections, especially with the flu making the rounds in the USA and Ireland. My irreplaceable Ibrutinib travels in my pants pocket so it is always with me.

The prep for a trip and the worry over what could go wrong is always the worst part. Once we are in Ireland, no matter how cold and damp, we will love it.

What makes that especially certain is that an internet friend whose wife has CLL is meeting us at the airport for a guided tour of the capital of his country, Dublin and then we will share a vegan dinner together. For a fanciful end to our very long day of travel and time shifts and touring, my wife and I will sleep in a real castle.

We can't wait to hit the road.

I am very lucky, but I got a ton of work to do before we leave for the airport.

One piece of personal medical news. Despite all the bone wasting corticosteroids prescribed with my infusions and other issues, and my stopping calcium, my bone density was unchanged in the last two years. I am still in the no man's land of osteopenia (not quite normal but not an an increased risk of fractures), but have not progressed to osteoporosis. I am crediting my high doses of Vitamin D3 and my weight training.

ASH 2012: Dr. John M. Pagel Part 2: Present Trials and Speculations on the Near Future of Ibutinib, GS-1101, ABT-199, GA-101, TRU-016 including Combinations and the Changing Role of Transplants

I am grateful for the thoughtful, caring and careful way Dr. John Pagel tells the evolving story of CLL treatment. But I am also grateful that he is willing to speculate about what the future might hold for us CLL patients and those yet to be diagnosed.

In the follow-up to Part 1 of my interview, Dr. Pagel hypothesizes a possible future of the "game changing" emerging therapies in CLL, their paths to probable approval, logical combinations, available and coming trials, the "boots on the ground" reality of how they will be used on and off label, and the reassessing of the time and place for allogeneic transplants.

His candid observation that drugs such as ibrutinib (PCI-32765) and GS-1101(now idelalisib and formerly CAL-101) will potentially be used extensively "off label" and upfront in therapy is in my opinion, a realistic take on what is coming to the next generation of CLL patients.

When he talks about the shifting role of allogeneic transplants, we hear his wisdom and experience gained from his years of helping patients in both the pre and post imatinib (Gleevec) eras.

He informs of us the logical combinations of agents, many with no cytotoxic chemotherapy to be found anywhere in the treatment protocol, that are available right now in clinical trials and will continue to be explored.

Please be sure to view Part 1 if you haven't already. It will help with the context of this continuation of the same interview. In Part 1, there is more indepth discussion of ABT-199. In Part 2, presented below, I start by asking him about the other two big names out there ibrutinib (PCI-32765) and idelalisib (GS-1101), and he picks up from there. 

There will be a brief Part 3 soon that will deal with transplants exclusively.

ASH 2012: Dr. John M. Pagel Part 1 Game changing medications including ABT-199, Ibrutinib, and GS-1101 for CLL

Here's a little New Year's Eve gift.

In the first of three segments of my interview with Dr. John Pagel,  he says some amazing things.

"this year from last year in CLL, it's game changing, it's night and day difference from where we're going and where we've come and what this field is evolving to, ...... evolving away from cytotoxic chemotherapy"

"this is an amazing wonderful time"

But enough of me quoting the scientist.

I will let the good doctor introduce himself and share some details about his personal experience and excitement concerning ABT199, ibrubinib, and GS1101.



As I attended more of the ASH science and education sessions, and as I interviewed more of the CLL champions, a more mature full screen story develops about the changes that are coming to the world of treatment.

Even a vegan can say that this isn't a case of too much sizzle, not enough steak. These changes are mighty and meaty.

This is really happening and it's happening fast.

In an upcoming post, I will outline some possible tactics for those of us whose urgent present need for treatment doesn't allow the luxury of waiting for the day in the not too distant future when we can go to our local pharmacy and pick up our bottle of pills to control our cancer along with our toothpaste and shampoo.

But first more, we have much more to learn from Dr. Pagel.

ASH 2012: Interview with Web Savvy Patient, Andrew Schorr

Andrew Schorr is a journalist, an advocate, and a very web savvy patient who has stared down CLL for about 16 years and it now winning his fight with myelofibrosis.

Through his helpful website, patientpower.info, he has provided a treasure trove of information for patients looking for answers.

Now he gets to be on the other side of the microphone in the hall outside the press rooms at ASH 2012. We learn from the interviewer turned interviewee about his strategies to navigate his disease. He outlines through his personal story and his decision process, the critical need for getting support from others with the disease, the primacy of expert advice, and the important role of clinical trials in saving his life.

In future posts, we will both share the interview he did of me about my ibrutinib trial.

Andrew and I have moved in the same CLL circles for several years now and I hope we keep doing it for many more to come.

Here is the interview:

Below is a photo of some of my local support group and our significant others at our holiday get-together. We don't look too bad for a bunch of patients with an incurable cancer, do we?

I would be lost without them.  If you have CLL, and don't have  support group, get one or join ours if you are local.

ASH 2012: Combinations of the PI3K∂ Inhibitor GS–1101 (CAL-101) with Rituximab and/or Bendamustine Are Tolerable and Highly Active in Patients with Relapsed or Refractory CLL

GS1101(formerly CAL101) was the first oral, exciting small molecule to show outstanding results in CLL after the failure of many other small pathway blockers.

It had about an 18 month head start on ibrutinib (formerly PCI-32765), but its lead has shrunk considerably in the race to FDA approval.

It too blocks the pathway downstream from the BCR (B cell receptor) that tells the clone to survive and proliferate. Bench research presented at ASH seems to suggest that in some clones of aggressive CLL with a higher tendency to Richter's Transformation, BCR is promiscuous (couples and responses with any old stimulating antigen) or in another poster presentation, may be self stimulating, perpetually turned on and driving the disease with no outside help. Quoting from the conclusions in that paper " These findings suggest the possibility of self-recognition of BCRs within the CLL cell membrane or BCR interactions between neighboring CLL cells. This may potentially result in autostimulation of the leukemic cell independent of “exogenous” antigens and may account for self-sufficient signaling of some CLL-BCRs in driving disease progression. "

Either way, turned on BCR is not our friend.

This basic science work applies to any and all drugs that effect the BCR pathway, and it was work such as this that lead to the idea that compounds such as GS1101 and ibrutinib might someday have a major role to play in controlling CLL. We now know that PI3K∂ drives survival and proliferation of the cancers cells, so blocking it with GS1101 makes good sense. 

That kind of hard work leads to an understanding  of the basic cell biology that leads to a treatment hypothesis that leads to animal studies that leads to human trials that leads to a usable drug.  I am way oversimplifying the story and this ideal path is aborted 99% of the time long before it gives birth to a helpful medical compound, but I wanted to share some of the mostly unseen effort that makes these breakthroughs possible.  The medicine bottle at the pharmacy is just the tip of the iceberg. We owed so much to the medical chemists.

So what were the clinical results with GS1101 that were presented at ASH? 

The important  abstract 191:Combinations of the Selective Phosphatidylinositol 3-Kinase-Delta (PI3Kdelta) Inhibitor GS–1101 (CAL-101) with Rituximab and/or Bendamustine Are Tolerable and Highly Active in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL): Results From a Phase I Study reported more good news: high response rates.

Here I am sharing an executive summary of the findings but you have a link to all the details included in the abstract. We must wait for the peer reviewed published paper as that is the true test of the validity of the research.

51 patients were studied in three different arms. These were not the easiest  of us to treat. All had relapsed after up to 10 prior therapies, 27 had refractory disease, more that half had bulky nodes, and nearly all had had prior B/R (bendamustine/rituximab).

In the group that was randomized to get B (bendamustine) with the GS1101, the intent to treat overall response rate (ORR) was 82%. Adding rituximab (the BR group) raised that to 87%.

But here is the number that excites me. Leave out the chemo (bendamustine) completely, and use only biological therapies with the combination of CD20 antibody, rituximab, and the new PI3K∂ inhibitor, the response rate was a very respectable 78% in these tough patients. 

Minimum follow-up was 40 weeks for each arm with the one year progression free survival numbers being very similar to the ORR.

Nodes shrunk rapidly in almost everyone. Disease related cytokines, elevated at the start of therapy fell, and that may explain why we feel so much better with these treatments. Elevated cytokines make us feel sick.

In the GS1101 + R (rituximab) group (only 19 patients), 21% (6 patients) got pneumonia, 32% had low neutrophils ( and 11% or two patients had febrile neutropenia) and 21% had low platelets. Only one patient had elevation of the liver enzymes. As expected, the blood work was considerably worse in the  two groups that received bendamustine. Surprising infections were lower in the BR group, but the sample was small with only 15 patients being followed.

The data are very encouraging, but we need much bigger numbers and longer time frames. That is the why we have the phase 3 trials, accruing right now. Check out clinicaltrials.gov for the details. My favorite would be the trial that offers either ofatumumab with or without GS1101 as a way to avoid a chemo arm.

But wait and discuss with your doctors the ibrutinib and ABT-199 trials too if you need to consider therapy soon. I will be reviewing those and some of the related important ASH abstracts here soon. Videos of my interviews with the experts at ASH are being rendered and prepared.

It is good to have choices. Not so long ago, we had almost none. 

Many reasons to be thankful and hopeful.

ASH 2012: CLL Highlights

I am still traveling, now in Ohio staying with friends for my OSU clinic visit with Dr. Byrd tomorrow. I am expecting that my mildly elevated neutrophils on my last blood draw will turn out just be an unexplained blip. I have other results from that prior visit that I need to discuss here too, but my personal story needs to take a backseat to the wonderful news from ASH for now.

I also have a photo shoot with the doctor, so I need my rest to look my best. More on that later.

When I am home, I will report in much greater detail on ASH 2012, Atlanta, GA, but I want to rush the news out about the big picture as soon as possible, so let me share some overarching highlights as I see them without the stats and scientific explanations behind them.

1. There has never been a year like this for those of us with CLL.
2. There is a palpable excitement and consensus among all the CLL doctors that treatment is radically changing for the better: a paradigm shift in therapy with the end of most chemotherapy possible in the next few years.
3. These new players are mostly oral therapies and are NOT traditional killers of rapidly dividing cells as is traditional chemo, but rather targeted biological drugs.
4. The stars of this sea change are GS1101 (formerly CAL-101), ibrutinib (formerly PCI-32765). and probably the least publicized member of this triumvirate, ABT-199 (a Bcl-2 blocker with amazing but less mature results).
5. Responses rates with these drugs in all comers, including the worst of the worst (think 17p del and refractory patients), are nothing short of astounding with progression free survivals in some treatment naive cohorts at 96% at about two years.
6. Responses get better, not worse, the longer we take these meds.The Kaplan-Meir curves are not falling. Relapses are remaining rare events, al least in the short term. We need longer follow-up for sure, but there is no signal that trouble is brewing,
7. Side effects are minimal and may actually decrease the longer we are on the medications.
8. The bone marrow is spared and infections at least with ibrutinib are not increased. Blood counts may actually improve with treatment.
9. With ibrutinib, there is some reason to believe immunity might improve
10. The data keeps just keeps getting better and better.

Much more to share about CAR-T, "off the shelf" CAR-T, GA-101, lenalinomide, the benefits of ASA and curcumin, and new encouraging data on 11q del, but I am badly sleep deprived so I am quitting here. Plus I need my beauty sleep for my photos.

Trust me that when I do fill in the details you will feel the same excitement that I felt humming in the air in Atlanta.

There is never a good time to get CLL, but there has never been a better time to get CLL.

ASH 2012: 10 Minute Break from the Excitement of the End of the Chemotherapy Era in CLL

Since I last posted I have interviewed Dr. Wiestner and Byrd, two of the most important researchers in moving ibrutinib forward. I also taped a long discussion with Dr. Wierda about CAR-T therapy among other things. Dr. Furman who did the phase 1 ibrutinib trial is next, then meeting Dr. Jeff Sharman.

This afternoon more lectures on ibrutinib, lenalidomide, and the first one on CAR-T.

Squeeze in the poster sessions and exhibit halls. And a visit with my sister-in-law.

Let me just summarize the news from ASH on CLL. You may not have heard it here first, but let me shout it out loud and clear.

The days of chemotherapy for CLL are ending. 

Details to follow.

Real Live Time at ASH 2012

I am posting this from the lecture hall at ASH with Jan Burger from MDACC speaking on ibrutinib and rituximab.

Forgive typos and possible errors. This is unedited and I may have made mistakes, so it is not gospel.

Here it is as it happens:

Study was in high risk CLL either 17 p or 11q del or < 3 yr response to FCR

Prior trial of ibrutinib alone good responses including the high risk patients, so more research.

This trial added R to see if helped, weekly x 4, then monthly x 6 months

Ibrutinib was given orally daily.

Enrollment criteria were these HR patients
Most patients Rai 3 or 4
Had average of 2.5 prior RXs
B2M elevated
50% 17p
33% 11q
80% unmutated

FINDINGS

As expected ALC showed rise at first then fell after months
Hgb climbed
Only 2 patients off study, or 38 of the 40 patients are still on study
Dramatic shrinking of nodes within weeks.
At 3-6 months more than 50% decrease in node size. No difference in 17p responses.
Same with shrinking spleen
At 3-6 month, 1 CR, ORR was 83%, 2 with SD
ADVERSE EVENTS:
20% diarrhea
Bone achy, No increased infections.
BIOMARKERS
CCL3 CCL4  too high at start, fell with Rx

That's it.

38 out of 40 doing well in the highest risk patients. That's amazing.