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.

Biologic and Immune Therapies for CLL (chronic lymphocytic leukemia)

Hi Friends,

This week’s update on the CLL Society website http://cllsociety.org is my unscripted recordings on biologic or immunotherapies.

I start by reviewing my take on the good and bad of the well known and novel antibodies directed against our B cells by targeting its surface marker CD20. These include rituximab (Rituxan), ofatuzumab (Arzerra), and obinituzumab (Gazyva). Among other topics,  I discuss the difference between type I and type II monoclonal antibodies.

I also cover other antibodies, new and old, IMIDS (immune modulating drugs) such as lenalidomide (Revlimid) vaccines, and more.

To listen please, visit the treatment section (found under the Basics tab) of the CLL website by clicking here: http://cllsociety.org/cll-101/treatment/

Please let us know if this helps. I am particularly proud of this recording as it was done live and spontaneously with no notes. I think is ends up being more focused, ironically similar to the drugs discussed.

We plan on bringing more of this type of content. Your feedback on the website or to me by email informs what we add and how we will grow the website. Although there is only myself, my wife (both unpaid) and a wonderful RN, Betsy Dennison as the team, we listen carefully to all comments to help brings what’s needed to best manage our cancer. 

Smart patients get smart care™.

As always, all our content is free and easily accessible to anyone but if you want you may sign up for our weekly alerts to know when we post new content, 1 to 3 x a week, and for our inaugural newsletters which will be amazing. We understand the importance of privacy and don’t share any personal info.

Our website traffic has grown phenomenally in its first 10 weeks. Over a 1000 page views on our busy days. We also hope it will be a launching site for anyone with CLL as we have links to nearly all the quality sites on our front page.

The artwork in the background of the video is again my son, Will Koffman’s tribute to Durer’s Four Horsemen of the Apocalypse.  Will rendered the entire work using only bleach on black cotton.

Nothing much new to report on the personal level with my CLL. Still get tired. Still traveling way too much (over the next 2 weeks I will be in Dallas, Seattle, Las Vegas and Poland to teach and to learn) and still doing too much and getting too sleep. Really it is a bit crazy.

I am waiting on my more granular lab results from OSU. Despite my best intentions, I always worry when I am waiting for my results.

Thanks.

Stay strong.

We are all in this together.

Brian

Volunteer Medical Director, CLL Society Inc.

http://cllsociety.org

BKOFFMANMD@GMAIL.COM

Three Year Anniversary on Ibrutinib for my CLL (chronic lymphocytic leukemia)

A Man and his Pills

On May 7, 2012, I swallowed my first three battleship grey pills of PCI-32765, later to be known as ibrutinib and finally Imbruvica when approved by the FDA for relapsed/refractory CLL in February, 2014. For us early adapters, most of whom like me, are still doing well in the subsequent extension trial, it is still the same grey pill and it is still called PCI-32765.

Clinical Trial NCT01217749 or PCYC-1109-CA out of Ohio State University (OSU) was a phase 1b/2 trial mixing the then very new BTK inhibitor with the then newest antibody, ofatumumab. I was in the last of three cohort. My group received the monoclonal antibody first so I actually started the trial a few months before I got to the ibrutinib. Details are described here.

Turns out that my cohort did the poorest as a bunch. Better to use the oral signal blocker first or even simultaneously to empty most of the cancer cells out of the marrow and nodes where the antibody can pick them off with no interference from their microenvironment enablers. That's why we do trials: do figure this stuff out.

But statistics predict for groups and here I am three years later in a deep deep remission. My absolute lymph count is at the low end of normal at 1000 and only 0.8% of those cells are clonal. If we do the math with just a few calculations we figure out that I only have 8 cancer cells in each microliter of blood. That not bad for someone who has a complex karyotype, 17p and 11q deletions, ZAP 70+, unmutated, CD38+, and a failed transplant.

Excellent disease control and a very deep remission, but not MRD negative. And certainly not cured.

For that elusive cure, I and most CLL patients will need a cocktail, preferably of target therapies. Fortunately some researchers agree and such trials are opening up.

During these last three years my blog has morphed from talking about my ups and downs in managing my CLL into a more universal story about the changing research and treatment paradigms in our disease.

Our newly launched nonprofit's CLL Society website: http://cllsociety.org will increasingly be taking on that educational role and my blog will return to being more my personal journey and the place for me to vent and pontificate.

Just this week, our website has several new articles: an article on the WHO statement on clinical trials, the news about the breakthrough therapy designation for ABT-199 or venetoclax for my fellow 17p deleted patients, and two cool interviews with Professor Roberts from Melbourne, part of our conference coverage,  which were done at ASH 2014. Dr. Roberts talks about the mechanism of action of and the early result with venetoclax or ABT-199, a drug that he helped develop in Australia.

Every Monday, Wednesday, and Friday we will be adding new videos and articles, so check back frequently. Already on some days, the one month old http://cllsociety.org is helping more folks affected by CLL than this venerable blog.

I have been asked by pessimists and worriers: How long and deep will the CLL Society's efforts at education, support, news, and advocacy continue? 

The answer is: As long as there is the need and the support for what we are doing, we will keep going.

Realistically, we desperately need to staff up in order to keep going at this pace and to expand what we are already doing. We have big plans that demand more than any one or two people can do, but we are just starting up and I am confident we will soon have the resources we need.

Stay strong.

We are all in this together.

Brian

Obinutuzumab in CLL (chronic lymphocytic leukemia): Rituximab with an Attitude

This second  OncLive video with Drs. Byrd, Furman, Kipps, and Ma was actually the first, the lead-in to my prior post. In fact the last few minutes of this video are the first few minutes of the video with the same doctors seen on my the recent post discussing ibrutinib.

Obinutuzumab is a powerful antibody directed against CD20 as is rituximab and ofatumumab but it seems to promise better responses as part of a therapeutic combination at least in some circumstances In this case when used with chlorambucil (a gentle form of chemotherapy or alkylating agent similar to cyclophosphamide, the C in FCR), it clearly delivered significantly deeper and longer responses than the other arms of the trial.

While the video session is clearly aimed at the oncology doctors, and our eyes may glaze over when there is a detailed discussion concerning the choice of the best steroid to use to abrogate the potential severe infusion reactions associated with this potent antibody, it is worthwhile to listen and catch the data on obinutuzumab.

It is nice to listen the experts for once discussing the real world concerns about cost and insurance.

It is also good to hear Dr. Kipps point out the critical role of the infusion nurses in keeping us well and safe.

Here is the results from the abstract published in the NEJM with Valentin Goede as the lead author. It is a study that randomized patients to one of three possible therapies: chlorambucil alone, or combined with either rituximab or with obinutuzumab. The trial patients were all untreated and would generally be considered to be too sick due to renal disease or other problems to risk more robust chemo-immunotherapy such as FCR.

Here is part of abstract results:

Obinutuzumab plus Chlorambucil in
Patients with CLL and Coexisting Conditions 

RESULTS

The patients had a median age of 73 years, creatinine clearance of 62 ml per minute, and CIRS score of 8 at baseline. Treatment with obinutuzumab–chlorambucil or rituximab–chlorambucil, as compared with chlorambucil monotherapy, increased response rates and prolonged progression-free survival (median progression-free survival, 26.7 months with obinutuzumab–chlorambucil vs. 11.1 months with chlorambucil alone;... and 16.3 months with rituximab–chlorambucil vs. 11.1 months with chlorambucil alone;

Please note that the impressive 10 month improvement in the mean progression free survival noted with obinutuzumab–chlorambucil compared to rituximab- chlorambucil. Comparison to chlorambucil monotherapy is not helpful as it is rarely used this way in the USA because of its known lack of efficacy.

CIRS score is a marker of the degree of co-existing illness.

It is important to remember that a benefit demonstrated with one combination is no guarantee that the antibody would demonstrate a similar benefit in any other combos. Assumptions can be dangerous in cancer care.

I am waiting for the published data that Dr. Kipps that show the results of the combination bendamustine and obinutuzumab.

Lastly, what we all really want (if we can't get a cure) is a durable remission. The mean progression free survival was a little over two years (26.7 months) for the mostly elderly treatment naive patients.

Is that enough for you?  Two years is nice respite, especially for a pretty gentle therapy used in a delicate population, but I wanted a longer time before half the group had to live with the reality of their cancer progressing again.

ASCO 2014: Dr. Sharman Reviews the Results and Implication of a Single Agent Obinituzumab Poster in CLL (chronic lymphocytic leukemia)

Another audio interview from ASCO 2014, this time with the ubiquitous Dr. Jeff Sharman, who with his work heading up a large national CLL/NHL research group, has brought us several important clinical results that has advanced our understanding of treatment options and provided directions for further research.

Here he is part of a group with Dr. Joe Flynn as the lead author, studying two different doses of the  fully humanized monoclonal type II antibody directed against CD20 (same target used by rituximab and oaftumumab) known as obinituzumab, also known as (AKA) GA101and AKA Gazyva used in this trial as single agent.

The abstract shows a strong trend to a better response with the higher dose, especially as regards complete responses. This is not surprising when we know from a dose escalation trial of rituximab published in 2001 from Dr. Susan O'Brien (mentioned in the interview by Dr. Sharman), that when it comes to antibodies, more is better.

Makes sense based on what we know about how these antibodies work. There are billions of B cells and only so much antibody. When they are all "bound up", there are none left.

There is also research now looking to see if there is similar dose response relation with CAR-T therapy: the more chimeric T-cells, the better, though the story here is much more complicated as it seems CAR-T cells are serial killers.

Dr. Kipps and I also discussed this same paper and the difference between Type 1 and Type 2 antibodies here. Dr. Jennifer Brown discusses earlier research on GA101 at ASH 2013 and the different types of antibodies here. And here are the details of its FDA approval and some of my comments only published only a little more than a year ago.

And if that's not enough background, here is an editorial from Blood 2012.

What a great year it has been for those of us touched by CLL! We are all on a fast moving train and while cure is still a distant light in the tunnel, long lasting low toxicity disease control for most of us may be a whistle stop that we blown past some time without even noticing some time last year.

Here's hoping.

Enjoy the audio interview with Dr. Sharman.


Thank you for putting up with all the pops and hisses again. I promise that they will be a thing of the past once I finish uploading the audio from ASCO 2014 and move forward to ASH 2014 and beyond.

Stay tuned as we have big plans that I will be announcing here soon that will improve our options for education and support for all of us with CLL and related B cell lymphomas in the near future.

ASCO 2014: Dr. Byrd: What we could only Learn from a CLL Phase 3 Trial about Ibrutinib and Ofatumumab in Relapsed CLL (chronic lymphocytic leukemia)

On the very last day of ASCO 2014 at the very last presentation, Dr. Byrd, my doctor out of Ohio State (OSU), shares with us what you could only find out from a Phase III trial.

But first I must apologize for all the popping from my holding the microphone too close to my loud mouth. Without any technical support for my audio recording, I did a lousy job on my own. But I have learned from my mistakes. Fortunately the important speaker in the interview, Dr. Byrd, is much more easily understood. Which is good because he has a lot of revealing thoughts and information to share. So despite the annoying pops, I decided to post this audio interview. There is a second section too on its way.

Dr. Byrd starts by explaining the important data that can only be discovered in a Phase III trial. Phase I is all about slow dose escalation and safety. While a Phase II trial is about watching for adverse events (AE) and sniffing around for efficacy, there is no comparator arm so anything bad that happens is automatically blamed on the trial drug to be extra cautious. But the bad happenstance may be just part of the background noise of the disease process, with or without the drug. There is no way to tell until we get to Phase III trials where we can see what happens and how often it happens to those on and off the novel therapy.

And we learned some surprises about AE with both drug with this trial. Here is a link to the abstract.

It also soon becomes abundantly clear to the trialists that ibrutinib was the far more potent drug for most patients. The difference in the responses with ibrutinib and with ofatumumab were so pronounced that all decent ethical standards forced a midstream redesign of the trial (and possibly all future trials) to allow a cross-over when there is such a wide gap between outcomes. Amazingly, even with the cross-over, ibrutinib still showed a significant survival advantage in the trial. That is good news for those of us on the outside looking in or those in the trial randomized to ibrutinib, but not for everyone: sadly it meant is that some patients on the ofatumumab arm had to die in order to prove the superiority of ibrutinib.

Dr. Byrd bravely and realistically takes on the issue of cross-over in trial design and getting drugs to market and those who need them.

He also discussed prognostic factors (the bad guys are the usual suspects: 17p deletion, complex karyotype, and perhaps three or more prior treatments). ASH 2014 will pick up this theme where it at least one abstract seems to say that complex karyotype is the ringleader of the bad players. I tend to agree. I have wondered aloud if 17p, the guardian of the genome, is just a surrogate marker for genes gone wild. This is personally annoying because I have a complex karyotype.

Later I think you can hear Dr. Byrd's pride in the new predictive tests that he and the team at OSU are developing to tell who is likely to progress on ibrutinib before they actually do.

Enough preamble. Let's listen to Dr. Byrd.



By the way, I wrote this entire blog post over the Atlantic Ocean on my way to Greece to lecture to hematologists on what patients want in their CLL treatment and also to attend and report from the ESH conference on B cell lymphomas.

Part two of my interview with Dr. Byrd to follow soon.

Want to avoid chemotherapy or taking an expensive medication foreverfor your CLL (chronic lymphocytic leukemia)? I may have a clinicaltrial for you.

METHYLPREDNISOLONE

I and many others have railed against chemotherapy for our CLL. It may give us a long remission, or not.  Your mileage will vary and those of us with anything but the best prognostics can be pretty sure that we will relapse too soon for our liking with a nastier clone. FCR may even cure a few very select low risk patients, though that is yet to be proven. But at what cost?  Possible bone marrow damage and immunosuppression leading to low blood counts, infections, and secondary cancers.

Many of us also worry about the risks and cost of being on a life long medication no matter how targeted and patient friendly it might be. This fear is not so much based on any evidence of a problem (as there are not many problems and the data generally keeps getting better as the years roll along), but more based on the opposite: the lack of evidence with any of the new oral agents about their real long term safety, because no one had been on them for more than five years at this time.

So that is why this trial at UCSD with Dr. Januario Castro deserves our consideration. Besides being the innovator in the research on HDMP, Dr. Castro is a super nice guy. Still, entering any trial is a huge decision and by its very nature is full of unknowns.

A PHASE IB/II STUDY OF OBINUTUZUMAB (GA101) IN COMBINATION WITH HIGH-DOSE METHYLPREDNISOLONE (HDMP) IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) PATIENTS. (GA101 & HDMP)

The team of Drs. Kipps and Castro and more recently Choi has been a leader for years in innovative less toxic treatments for CLL. HDMP especially in combination with rituximab or ofatumumab has proven efficacy in all flavors of CLL including those of us with the stubborn 17p deletion. Here is link to an article on HDMP+R in frontline therapy. I quote:" With over 3 years of follow-up median progression-free survival was 30.3 months with only 39% of patients requiring additional therapy, and an overall survival was 96%." Similar results have been published here with HPMP + ofatumumab.

There are reasons to believe that this new trial may do even better. Obinutuzumab is a more potent mAb (monoclonal antibody) than its predecessors.  Remember that when it was combined with chlorambucil it proved superior to ritximab: This abstract from NEJM states: "Treatment with obinutuzumab–chlorambucil, as compared with rituximab–chlorambucil, resulted in prolongation of progression-free survival." Its 20.7% complete response rate in combination with wimpy chlorambucil is also encouraging, so it suggests that adding Gazyva to another cytotoxic agent, in this case HDMP makes good sense.


Not that either HDMP or obinutuzumab are without their risks. HDMP can cause a short term increase chance of serious infections, diabetes, fluid retention and psychiatric issues to mention but a few of the possible adverse events. Gazyva can be associated with scary infusion reactions. One definitely needs a team that has experience with this heavy weight arsenal. USCD certainly does. And the good news is that neither therapy is myelosuppressive and neither should have long term sequelae.

The rap against HDMP, justified or not, is that the remissions have not been that durable. This trial hopes to squash that story. But no one knows. That's why it's called a trial.

So are you interested?

The best news is that unlike other trials for attractive therapies where inclusion criteria may be fairly narrow, this trial welcomes nearly all comers. See below. I especially like: A. Documented refusal to be treated with chemotherapy agents.  Do you think patient advocates may have been a factor in kicking open the gate that wide? Here are some of the inclusion criteria copied from clinical trials.gov.

Laboratory parameters as specified below:

• Hematologic: Hemoglobin > 8 g/dL (may be post-transfusion); platelet count > 40 x103/mm3 (may be post-transfusion). Absolute neutrophil count > 1.0 109 cells/mm3 (Growth factor use is allowed).
• Hepatic: Total Bilirubin < 3 x ULN, and ALT and AST < 3 x ULN
• Renal: Creatinine clearance > 30 mL/min (Calculated according to institutional standards or using Cockcroft-Gault formula. Subjects with requirement of hemodialysis will be excluded).

Subjects can be enrolled and treated under this protocol regardless of their CLL treatment history or number of previous treatments. In addition, subjects with history of allogeneic stem cell transplant can be enrolled and treated unless they have active manifestations of graft vs. host disease (GVHD) or chronic illness or infections that will prevent them from completing the study.

Previously untreated subjects that meet ANY of the following criteria: A. Documented refusal to be treated with chemotherapy agents. B. Subjects that are not candidates for treatment with chemotherapy based on poor performance status (ECOG ≥ 2), advance age (> 65 years), Cumulative Illness Rating Scale (CIRS score) ≥ 6 or cytopenias.

These are extraordinarily liberal rules for eligibility for any trial.

I don't know where HDMP+OB will fit in. No-one does. That's why we need this trial. It is particularly attractive to anyone who want to avoid chemo (who doesn't), is willing to document their reluctance, and does not qualify for other non-chemo trials. But it also should appeal to any of us with 17p deletion or any of us who just want to have six months of non-chemo treatment and then hopefully coast for a long long while.

Finally to be clear, I don't have any personal connection with this trial other than my history of being a patient at UCSD. Moreover, while I believe that for some of us, it is worthy of careful review for the reasons I have detailed, the decision about entering any trial must be personal and cautiously weighed. Thankfully there are growing numbers of non-chemo and chemo options out there.

It's all a gamble: hope as I am doing to ride a TKI (ibrutinib) into the happy ever after sunset or whack the CLL hard monthly for half a year and pray that it is so far gone that it ain't ever coming back.

Sunset at Corona del Mar

IF YOU WANT A PERSONAL RESPONSE OR TO JUST STAY IN TOUCH, PLEASE SEND YOUR EMAIL ADDRESS TO BKOFFMANMD@GMAIL.COM AS I OTHERWISE DO NOT RECEIVE THEM.

Forbes says: "With So Many Terrific New Drugs For Chronic Lymphocytic Leukemia (CLL), Why Worry?" I say it's a Tempest in A Teapot

Hydra (mythical monster that grows two heads when you cut off one)

Elaine Schattner wrote a provocative and helpful editorial in Forbes: With So Many Terrific New Drugs for Chronic Lymphocytic Leukemia, Why worry? I recommend we all read it, but that we also read it critically.

It has to do with her concerns about the dangers of unnecessary treatment.

My friend and fellow cancer advocate Andrew Schorr wisely reminds of us a friend with CLL who has done very well without treatment for nearly 18 years.

We know that about three out of every ten of us diagnosed will follow a very indolent (slow) course and never need treatment.

And so the author cautions us to avoid unneeded therapy. Good counsel. Never take a treatment that's not needed. All drugs and I mean all drugs have side effects. 

Her concern and motive for her editorial is that thousands of us will rise up demanding that our hematologists offer us the new expensive therapies just because they are so darn safe and effective when we would be better off doing nothing, just watching and waiting. Hordes of CLL patients will ignore the carefully tuned 2008 iwCLL guidelines on treatment, and demand an immediate prescription NOW before we are in troubled waters.

I believe it's a false concern. 

A powerful and practical reason that Ms. Schattner is worrying over nothing is that these expensive drug are not yet approved frontline  with the notable exception of ibrutinib in 17p deleted patients as detailed in this recent post). It is highly unlikely our medical insurance is going to pay for an off label use of a pricey therapy when there is ZERO data to support it. And of course, there are vanishingly few of us that could afford the out of pocket cost of at least several thousand dollars per month for any of the new star therapies (in order of appearance on the CLL stage): ofatumumab, obinutuzumab, ibrutinib and idelalisib. And of course, even frontline approval is not the same as approval (and insurance coverage) when there is no indication to treat.

That said, I am sure that there will be a few patients among us who will think it is the height of craziness to sit on our hands. We should strike the cancer while is still in its infancy well before it has the time to achieve its typical mature persistence and wily ways, making it such a formidable foe, making a cure still a dream for almost all of us. Kill it before it grows into a multi headed hydra.  

But a quick review of the facts should dissuade us from this tempting but false path. There is absolutely no evidence that early intervention helps. In this oft quoted article from 1988, Treatment of early chronic lymphocytic leukemia: intermittent chlorambucil versus observation, and this one from the NEJM in the same year show we learned that there was no survival advantage to early intervention. And there are certainly risks. Studies such as these reinforces the importance of knowing the data and also knowing where there is no data.

Wait you say: Chlorambucil may have been state of the art in 1988, but today we have better therapies. Might not the results be different if we looked again using today's drugs? 

Good question. The same sort of trial was set up with FCR, but died on the vine due to lack of enrollment.

That is why trial such as this closed trial on using lenalidomide or this new one using ofatumumab are so important and need our support.

Although prognostic factors such as FISH and ZAP 70 and mutation status tell us much about a group of individuals and little about the individual members of that group, wouldn't we all want to jump out of the high risk frying pan and get far far away from the heat in the kitchen to a calm and cool place of low risk if we could do so by intervening early?

That's is exactly why we need more studies to answer if it is possible to save more lives by using the new mAbs such as ofatumumab and obinutuzumab and the new TKIs such as ibrutinib and idelalisib and others in the pipeline before we traditionally need treatment. There is good reason to believe it just might be so, but without data…. it's only conjecture.

So what do I recommend?

I believe all these drugs should be moved towards more frontline therapy for all patients with the help of well designed trials,  not just those of us with high risk prognostic factors.

I believe these drugs should be studied in those of us with high risk unstable disease BEFORE we need treatment. 

And maybe I am about to sound like a doctor when I say this: I also believe that outside of a clinical trial, there is absolutely no role for these drugs for patients who don't meet criteria for treatment.

The Forbes editorial ends with some sage advice:

“As with other malignancies, the best way to prevent overtreatment is to assure that doctors are current in their education, knowledgeable of “lesser” treatment approaches, and not motivated by financial incentives to give therapy. And for patients, the best prophylaxis is to know that not all conditions carrying a malignant label warrant treatment. Patients might ask, “What’s the least toxic therapy you can give, so that I’m likely to stay alive with the quality of life I want, with this particular form of cancer?”

That's precisely what we are trying to do here. Educate doctors and patients about low toxicity options.

IF YOU WANT A PERSONAL RESPONSE OR TO JUST STAY IN TOUCH, PLEASE SEND YOUR EMAIL ADDRESS TO BKOFFMANMD@GMAIL.COM AS I OTHERWISE DO NOT RECEIVE THEM.

Approval of Imbruvica Frontline for 17p deleted CLL (Chronic Lymphocytic Leukemia) and Important Trials

It's old news (July 28, 2014), but worthy of some reflection that ibrutinib ( PCI-32765 or Imbruvica) was approved frontline in CLL for those of unfortunate enough to have a deletion of the short (petite or p) arm of chromosome 17.

The p53 gene lives on the 17p arm so when it's deleted, there's missing p53. Without functional p53, cancer cells don't die very easily of apoptosis, the programmed death pathway built into all cells that allows them to suicide when they get too old to function, or in the case of our leukemic cells, become increasingly aberrant and dysfunctional. Without  the tumor suppressing p53 gene, the "guardian of the genome", protecting and repairing our DNA and if that fails, then starting to fire up the self destruction pathway, our cancer continues to grow and mutate and get weirder and more aggressive and difficult to treat.

Most chemotherapy works with the help of p53, first damaging the DNA itself, but then needing the p53 to take it from there by recognizing the overwhelming damage and then persuading the injured cell to die. No p53, and we get just the  chemo induced DNA damage, but the cell can live on and even reproduce faulty clones of itself. That is one reason 17p deletion carries such a bad prognosis.

Until we had ibrutinib (and now also idelalisib or Zydelig), our choices for treating 17p deleted CLL were poor- There were and are a few other therapies that do their killing independent of p53 induced cell suicide. Campath works if you don't have any big nodes, but comes with high infection risks. HDMP (high dose methylprednisolone) + R (rituximab) and flavoperidol and even lenalidomide helped some.

No great choices, until now.

I quote from the press release about the trial that lead to the ibrutinib approval:

At baseline, the median age of these patients was 67 years, 58% of whom had at least one tumor  >  5 cm, and 32% of whom had the del 17p mutation. Patients receiving IMBRUVICA demonstrated a statistically significant improvement in progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) as compared to patients treated with ofatumumab. The median PFS and OS has not been reached on the IMBRUVICA arm. There was a 78% statistically significant reduction in the risk of progression or death as assessed by an independent review committee (IRC) according to the modified IWCLL criteria (HR 0.22, 95% CI, 0.15 to 0.32). In addition, the analysis of overall survival demonstrated a 57% statistically significant reduction in the risk of death for patients in the IMBRUVICA arm (HR 0.43; 95 CI, 0.24 to 0.79). This was observed despite a total of 57 patients who were initially randomized to ofatumumab crossing over to receive IMBRUVICA prior to the analysis. For previously treated del 17p CLL patients, there was a 75% reduction in the risk of progression or death as assessed by an IRC (HR 0.25, 95% CI, 0.14 to 0.45).

Ibrutinib seems to do well on all the folks like me with a missing 17p chromosome on our FISH test, and probably even better for the treatment naive 17p deleted patient. Here is another abstract from the NIH on the subject.

This is good news, right now for just those 17p deletion frontline, but I hope it is only the beginning.

I believe these drugs and others in the pipeline need to be available to all appropriate treatment naive patients, not just those with 17p deletion.

It shouldn't be that most of us have to fail chemo first before being offered less toxic options. The ibrutinib data from the earliest trials suggest those who get ibrutinib upfront before any chemo do the best.

That is why there are some really important clinical trials out there to consider for those who will soon be needing their first treatment for their CLL. Here are a few of my favorites.

With ibrutinib or Imbruvica:

Rituximab and Bendamustine Hydrochloride, Rituximab and Ibrutinib, or Ibrutinib Alone in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia

Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

With idelalisib or Zydelig or CAL101: 

A Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated CLL/SLL

A Study of Idelalisib and Rituximab in Elderly Patients With Untreated CLL or SLL

Efficacy and Safety of Idelalisib in Combination With Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia With 17p Deletion (Havasu)

Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab in Subjects With Previously Untreated Chronic Lymphocytic Leukemia

With ABT-199 or GDC-0199:

A Study of GDC-0199 (ABT-199) in Combination With Obinutuzumab in Patients With Chronic Lymphocytic Leukemia

This is by no means a complete list. There are at least 222 trials when you search untreated CLL on Clinicaltrials.gov.

These trials are critical so we can finally prove, as I suspect, that moving these drugs upfront and avoiding chemo all together, is our best course for a long and healthy life.

There are a few other exciting early trials using ROR1 for relapsed disease that Dr. Kipps will be discussing in my next post, an interview from ASCO. ROR1 may prove to be the holy grail of a marker that is truly unique to the CLL cells, making it the perfect target for an anti-cancer drug.

UC-961 (Cirmtuzumab) in Relapsed or Refractory Chronic Lymphocytic Leukemia

This is with a very exciting and very specific antibody developed by Dr. Kipps' team at UCSD. It should be opening very soon.

Autologous ROR1R-CAR-T Cells for Chronic Lymphocytic Leukemia (CLL)

This is from Dr. Wierda's team at MDACC and CLL Global Alliance, building on the promising work out of U. Penn with CART-T cells directed at the much less specific CD19.

Both these are phase 1 trials with all the risks and possible breakthroughs that come with being early to a new therapy. My ibrutinib trial, though later in development, was still a phase 1/2 trial.

There are growing choices out there for those of us facing therapy for the first time, and for those who have relapsed. 

Clinical trials are the only way our knowledge can grow, and the only way these drugs will ever become widely available.

And clinical trials are for many of us, especially in frontline settings, the only path to getting these new agents. 

Speaking of new drugs being available, July 28 was also the date that the FDA gave final approval for Ibrutinib for those who have received one prior therapy. The accelerated conditional approval six months ago had been based on phase 2 data, the final approval looked at the big phase 3 RESONATE trial data.

More from Dr. Kipps on ROR1 soon from our interview at ASCO 2014.

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.

ASH 2013: Dr. John Pagel Discusses the Risks and Benefits of ABT-199 and TRU-016 or otlertuzumab in CLL (chronic lymphocytic leukemia)

In the final segment of my interview with Dr. Pagel from ASH 2013, he discusses ABT-199 and TRU-016 or otlertuzumab (yet another mouthful for us to poor patients to learn and pronounce).

We have heard much already about ABT-199. Here is a link to a trial reported at last year's ASCO meeting and I have an interview pending from ASH 2013 with Dr. Seymour from Australia. At ASCO later this week, there will more news on ABT-199 with a new dosing schedule to reduce the risks of tumor lysis syndrome (TLS).

TRU-016 is another under reported therapy, a potent monoclonal antibody (MAb), much like rituximab, that is as of now only available in clinical trials. In my opinion it has not received the attention it deserves. Unlike rituximab or ofatumumab or even obinutuzumab that all target CD20, TRU-016 targets CD37. But like CD20, CD37 is also found on most mature B cells, both cancerous and benign and much less so on T cells making it is a good choice for fighting CLL. That's an important difference from Campath that binds to CD52 and destroys both B and T cells. With no T  or B cells to fight infection coupled with our already wimpy immunity, we are high risk for life threatening infections. TRU-016 did not increase infection risk in this small trial.

Here is the ASCO abstract that compares bendamustine with or without TRU-016. The number were very small, but for those who received TRU-016 there was responses in the two patients with 17p mutations but not in the two with 17p deletions. As expected, there were no responses to single agent bendamustine.

And here is Dr. Pagel:



I am hoping to sneak one or two more post before I take off for ASCO 2014 later this week.

ASH 2013: Dr. Jennifer Brown Discusses the New Data on Obinutuzumab (GA-101 or Gazyva)

At ASH 2013, there was much to celebrate for those us with CLL.

This interview was recorded immediately after Dr. Jennifer Brown of Dana Farber had moderated an exciting CLL press conference in that same noisy press room.

While the small molecules that can be taken orally such as ibrutininb, idelalisib, ABT-199 and even the newer IPI-145 and ONO 4059 may have hogged much of the headlines over the last few year in the CLL world, there was important news about a new and better monoclonal antibody or mAb, namely obinutuzumab.

This one, like rituximab and ofatumumab, is directed against CD20, a surface protein found on all B cells, good and bad.

So like its fellow anti-CD20 mAbs, obinutuzumab knocks out all our B cells, leaving us at an increased risk for new infections and reactivation of old ones such as hepatitis B.

A bit of a background on another mAB first.

I have to say after all the excitement following the the approval of the second generation fully humanized CD20 antibody, ofatumumab, I have been disappointed in the results. Its main advantage seems to be for anyone allergic to rituximab, lovingly called "mouse juice" by the thousands of us who have had it dripped into our arms at infusion centers across the world because of its unholy but magic mix of mouse and human proteins (especially strange to think about if you are vegan like me). Despite high doses of pre-medications with steroids and antihistamines, some of us patients just can't get our bodies to stay calm in the presence of the mouse antigen and let the antibody do its important work. That is where ofatumumab has shined. No mouse proteins, so those who could not tolerate "Vitamin R" had an option. But the impressive improvement in efficacy over rituximab that I and many others were hoping for has not really materialized.

Obinutuzumab tells a different story. People are living longer significantly longer as Dr. Brown will detail on camera. The results are clearly better. The bar with rituximab was already set pretty high. Rituximab might be a lousy CLL drug on its own, but as a dancing partner it makes everyone look like a Fred Astaire (or Ginger Rogers). Its addition to FC forming the "gold standard" of FCR was the first time that any therapy was shown to prolong survival in CLL.

Dr. Brown of Harvard now gives us even better news on obinutuzumab.

But first we review how it was engineered to get these strong results and explains why being the first type 2 anti-CD20 antibody is so important to its efficacy.

And she discusses the management of the higher risk of infusion reactions. Please remember that although these new antibodies have no murine proteins, they can still cause rather severe infusion reactions, precisely because the bind so strongly to our B cells and are such potent killers.

Here is Dr. Jennifer Brown:



Remember too that this drug is already approved for CLL. From the package insert: in combination with chlorambucil, is indicated for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).

As I have reviewed in a prior post, this is a very limited indication, and much of its benefit would be expected to come in its use with other more potent combinations than with chlorambucil and for patients who have relapsed or who are refractory to other therapies including other mAbs. I would hope that it appropriate use off label is not rebuffed by the payers.

I expect soon to see a growing number of trials mixing and matching the new TKIs with obinutuzumab to get us that elusive CR. We need more trials. To get to our ultimate goal, a cure, we must first get to and pass CR, and most of the TKIs are leaving stalled on 3rd base with some persistent measurable disease. These new oral wonder drugs still need a teammate to get us home to a cure, and obinutuzumab is a very strong candidate to play that role.

That is the future I want. Rational non-chemo combinations edging us closer to a cure. It can't come soon enough. But we need more creative trials and more brave risk takers to make them happen.

The News about Ibrutinib from My Infusion Chair, The Resonate Trial, and Lancet Oncology

Yesterday, I was at the infusion center for my IVig and got back one of the most normal lab results since my diagnosis. No anemia, normal neutrophils and lymphs and a healthy platelet count. Chemistry panel was fine too. LDH and uric acid  in the healthy range.

I credit my wife's famous cajun gingerbread, full of iron in the guise of blackstrap molasses.

I had stretched out my infusions to every 8 weeks and was rewarded with a very nasty respiratory infection just before ASH. Although I take my IVig for ITP and not for infection prevention, I sure didn't mind if I enjoy a twofer. 

Let me pause here for a minute. If I can go a full 8 weeks with little drop in my platelets, it could be argued that I don't need the IVig. One could question if there enough of it around after almost two months to be doing whatever it does to protect my platelets from destruction? However my blood level go IGG was still >500 at the 8 week mark, lower than normal, but still respectable and suggesting to me that it still may be having an impact on stopping the auto-immune process.

The only way to "test that hypothesis" is to "test that hypothesis", and with my few near death experiences with single digit platelets and bleeding fading into my past, there is no way I am risking a return to that wasteland. That is why I have been so slow and deliberate in extending the time between infusions.

in terms of the other advantage of the IVig, did my first bad infection since my transplant comes as a result of going 8 weeks between getting my IGG topped up? My local oncologist, Dr. Sharma, thinks not and that it was just my bad luck. If he is right, the flip side might mean that my five years of being infection free were also not a result of the infusions of someone else's antibodies. 

I have decided to play it safe and drop back to 6-7 weeks between visits to the infusion chair.

Now let's talk about what's going on not to this single trial rat, but to a whole swath of brave volunteers.

The press release below from Pharmacyclics  (click on the 1st PR) tells us what many of already expected based on our experience and that of fellow CLLers: Ibrutinib is a superior treatment for many of us.

Sure is for me and a bunch of friends.

So positive were the results that when the independent team looked at the data, they decided to stop the trial because it would have been unethical to continue as those getting ofatumumab were not doing as well as those on imbrutinib.

This can only help move the time of approval for CLL closer, but since this trial was on relapsed and refractory patients, those wanting ibrutinib frontline are likely to be left wanting. The FDA works in mysterious ways so but I am hoping for a quick and broad approval in the next two months. 

The second article from Medscape reviews the same study but also reports on the data out of Dr. O'Brien's phase 1b/2 trial of monotherapy  just published in Lancet.  Ibrutinib in treatment-naive elderly patients had a mildly disappointing 71% response rate and an encouraging 13% complete response rate. Side effects were the predictable, with more than two of three in the study having diarrhea. There was one patient who did have a serious drop in the platelet count.

Here is the 1st press release:

SUNNYVALE, Calif., April 18, 2013 /PRNewswire/ -- Pharmacyclics, Inc. (Nasdaq: PCYC) announced today that the enrollment target of 350 patients for its Phase III study using ibrutinib monotherapy versus ofatumumab in patients with relapsed or refractory chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL), (RESONATE™) was achieved on April 3, 2013. As of today, additional 41 patients were screened and are allowed to participate in this study which has now been officially closed to enrollment.

The primary endpoint of this study is to demonstrate a clinically significant improvement in progression-free survival with ibrutinib when compared to ofatumumab. A pre-defined number of progression events will trigger an interim analysis. We would expect to have a read out from the interim analysis during the 1st quarter 2014. If the treatment effect of ibrutinib in comparison to ofatumumab is deemed statistically favorable by an independent review committee a discussion with the FDA and other health authorities for a potential early filing can take place.

"In addition to our outstanding team, we are grateful to the patients, their treating physicians, and the clinical sites for their participation in our RESONATE study and their strong support of the ibrutinib program," said Maria Fardis , Chief of Oncology Operations and Alliances at Pharmacyclics.

Pharmacyclics also announced the completion of enrollment of the planned 110 patients in the Phase II single-arm study using ibrutinib in patients with mantle cell lymphoma (MCL) who progress after bortezomib therapy and have received at least one prior rituximab-containing chemotherapy regimen, SPARK (MCL2001). This global study is conducted by Janssen Research & Development, LLC, and its primary endpoint is overall response rate, which is scheduled to be evaluated 6 months from the completion of enrollment. Further updates to this study will be provided by Janssen.

As previously announced Pharmacyclics expects to file a New Drug Application (NDA) with the FDA for the use of ibrutinib in patients with relapsed or refractory MCL prior to year-end. In the time before a potential U.S. marketing approval Pharmacyclics will strive to provide early access to ibrutinib under an Early Access Program (EAP). EAPs are clinical studies and allowed under certain circumstances by the FDA. They are designed to provide a mechanism for access to an investigational drug to treat patients with a serious or immediately life-threatening disease or condition until the time of an anticipated U.S. marketing approval. A multicenter, open-label EAP, conducted by Janssen, will be initiated in the United States with ibrutinib for relapsed or refractory MCL patients. Information about this program is posted and updated on www.clinicaltrials.gov.

"The completion of the enrollment of our first Phase III study with ibrutinib, ahead of schedule, is an important milestone for our clinical development plan and a real achievement for our company," said Bob Duggan CEO and Chairman of Pharmacyclics. "As of today we have initiated 5 Phase III studies together with our partner Janssen and we currently have registered with the US National Institute of Health 28 clinical trials using ibrutinib. Thus far over 1200 patients have been dosed in our studies and we are making excellent progress in the development of this investigational drug, as underscored by the most recent three Breakthrough Therapy Designations we received from the FDA. It is Pharmacyclics' goal to advance science and drug development in the hopes of making a significant difference for the betterment of patients with serious unmet needs, and we are steadily progressing towards that worthy goal."

About Ibrutinib

Ibrutinib was designed to specifically target and selectively inhibit an enzyme called Bruton's tyrosine kinase (BTK). BTK is a key mediator of at least three critical B-cell pro-survival mechanisms occurring in parallel – regulation of apoptosis, cell adhesion, and cell migration and homing.

The effectiveness of ibrutinib alone or in combination with other treatments is being studied in several B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, Waldenström's macroglobulinemia and multiple myeloma. To date 5 Phase III trials have been initiated with ibrutinib and a total of 28 trials are currently registered on www.clinicaltrials.gov. Janssen Biotech, Inc. and Pharmacyclics entered a collaboration and license agreement in December 2011 to co-develop and co-commercialize ibrutinib.

Ofatumumab is manufactured by Glaxo Group Limited and distributed by GlaxoSmithKline.

Bortezomib is marketed and distributed by Millennium Pharmaceuticals, Inc.

SOURCE Pharmacyclics, Inc.

Here is the second article from Medscape. My trial doctor, Dr. Byrd participated as did many whom you have seen interviewed here. The article has links to the publication in Lancet. Thanks you Medscape for this nice overview.  Dr. Brown raises the unanswered questions about timing, combinations (she mentions the combo with rituximab, but I would vote for obinutuzumab myself), and relapse with Richter's.

CLL Trial Stopped as Ibrutinib Shows Significant Benefits

Zosia Chustecka

January 09, 2014

A phase 3 clinical trial in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) has been stopped early after significant benefit was seen with ibrutinib (Imbruvica, Pharmacyclics/Janssen).

The novel drug, a first-in-the class inhibitor of Bruton's tyrosine kinase, is currently awaiting approval for use in CLL (with a decision expected from the US Food and Drug Administration before the end of February); it was approved in November 2013 for use in mantle cell lymphoma.

Ibrutinib has stirred up considerable excitement in hematology circles, with experts describing it as a "turning point" in the treatment of CLL and "a step change" in the treatment of mantle cell lymphoma.

The trial that has just been stopped because of benefit, known as RESONATE, was a phase 3 study conducted at more than 70 clinical sites across 10 countries. It involved 391 patients with relapsed or refractory CLL or SLL who had received at least 1 previous therapy. A head-to-head comparison trial, it pitched the oral drug ibrutinib against the intravenous drug ofatumumab (Arzerra, GlaxoSmithKline), which was approved for CLL in 2009.

According to a press release from Pharmacyclics, an interim analysis of this trial showed that patients on ibrutinib had a statistically significant improvement in progression-free survival (the primary end point of the study), as well as in overall survival (a secondary end point), when compared with ofatumumab.

No further details were given, and the results are due to be presented at an upcoming meeting.

As a result of this finding, the Independent Data Monitoring Committee recommended that the trial be stopped and that any patients on ofatumumab be offered treatment with ibrutinib.

Earlier Trial Now Published

An earlier trial with ibrutinib showing "encouraging" efficacy in elderly patients with previously untreated CLL has just been published in the January issue of the Lancet Oncology.

The results come from a phase 1b/2 study, conducted in the United States, of 29 patients with CLL and 2 patients with SLL who had previously not been treated. (This was a part of a larger study — the greater part of this study was conducted in patients who had been previously treated, and these results were reported last year.)

All patients were at least 65 years of age, and most patients (74%) were at least 70 years old. They all received oral ibrutinib once daily at a dose of 420 mg (some initially received the higher dose of 840 mg, but this was discontinued after comparable activity of the 2 doses was shown).

After a median follow-up of 22.1 months, a complete response was reported in 4 patients (13%), a partial response in 17 (55%), and a nodular partial response in 1 (3%). The overall objective response rate was 71% (22 of 31 patients).

The authors, led by Susan O'Brien, MD, from the University of Texas M.D. Anderson Cancer Center in Houston, say the trial shows that ibrutinib is well tolerated and effective in older patients with CLL, and support the continued assessment of this drug in this population of patients.

Notably Good Toxicity, But Questions Remain

In an accompanying comment, Jennifer Brown, MD, from the Dana-Farber Cancer Institute in Boston, comments that the toxicity profile of single-agent ibrutinib was "notably good, with low myelosuppression and few infections," and this makes it "potentially very appealing as a therapeutic option, especially for elderly patients."

An interesting feature of ibrutinib activity is that most patients have prolonged stable remissions (i.e., persistent disease, rather than complete remissions), Dr. Brown comments. However, this persistence of disease does raise the concern that resistant clones can emerge over time, she notes, adding that this has been reported in patients who have relapsed on ibrutinib

An additional concern is that this may result in Richter's transformation, in which CLL is transformed into an aggressive lymphoma, which can be fatal, she adds. This has also been reported in patients who have relapsed on ibrutinib (in 1 patient in this current study, and in 7 of 11 patients in the other part of this trial).

These concerns emphasize some of the remaining questions on how to best use ibrutinib, and in particular if it may be best to use the drug in combination with an agent that produces deeper remissions, Dr. Brown adds.

The only agent so far to have shown an early definitive overall survival benefit in CLL is rituximab (Rituxan, Genentech/Roche), and hence a combination of ibrutinib with rituximab is very appealing — and trials of this combination are in progress, she notes.

Despite the unanswered questions, there is hope that ibrutinib, which is the first of several extremely active novel agents coming out of development, will lead to "striking benefit for patients in the coming years," Dr. Brown comments.

Lancet Oncol. 2014;15:3-5, 48-58.  Abstract

The research is moving forward, but there are still leaves so many questions unanswered and I am so impatient.

Paul Henderson Battles Back Against Cancer

Paul Henderson and me in Niagara Falls

Thank you, Toronto Sun for this good news story in your hockey section.

OK, I am still a Canadian.

OK, I am still a huge hockey fan.

OK, I still remember the goal he scored against the Soviets.

When we met in Niagara Falls in 2012 at CLLPAG conference, I suggested he look into the NIH trial for ibrutinib. At that time, I had not yet started ibrutinib, but was still in the ofatumumab stage of the clinical trial at OSU with Dr. John Byrd where I would eventually get ibrutinib and do so well.

I am glad to see he is having the extraordinary success that I and so many others are enjoying with ibrutinib and the other new medications for CLL.

I am moved but his spiritual response to his cancer challenge. Paul is a man of faith and this is the season of miracles.

I hope and pray that the cost of these medicines will not delay their access in Canada- in every province, for every patient that would benefit.

I salute Paul Henderson for getting on a plane and flying to Bethesda. Not everyone has the resources or the knowledge or guts to do that. Not everyone fits the admission criteria for a trial.

I want to build a CLL community where every patient across all borders has the opportunity for the best possible care.

I am traveling, having met with other blood cancer patient advocates in Greece, so I appreciate the Toronto Sun doing my work for me on this post. Little time to write here.

One comment:

The hockey great tells the truth when he says what we know is that ibrutinib will work for about two years, but that is only because that is the best data we have. Only a handful of patients have taken it for around 4 years now and nearly all of those are still cruising along with their disease controlled, but the truth is that most of the data is out about two years or less. The curves are very flat for the treatment naive (those whose first treatment is ibrutinib), meaning that nearly all do not develop resistance and are doing great. In the relapsed and refractory population, the great majority also continue to respond, but there is a slightly bigger drop off. There are clearly some late CLL relapses seen after a year or more on drug, mostly seen in those with genomic instability such as those of us with a deletion 17p. More on this with the exact statistics from the papers at ASH when I get back stateside.

When I get home, I promise that I will write more about the news about CLL from iwCLL and ASH.

But first this feel good article.

BY JOE WARMINGTON ,TORONTO SUN
FIRST POSTED: MONDAY, DECEMBER 16, 2013 09:50 PM EST | UPDATED: MONDAY, DECEMBER 16, 2013 10:48 PM EST
TORONTO - 

All Paul Henderson wanted for Christmas was a clean bill of health from his deadly cancer.
It was actually more his wife of 50 years, Eleanor, their three daughters — Heather, Jennifer and Jill — and seven grandkids who were doing the asking.

It was no secret it was wishing for a lot. A miracle may be more what they were praying for.

It was not looking promising.

Just a year ago, the thought that the legendary Canadian hockey hero, suffering from chronic lymphocytic leukemia, would even be around for another Christmas was a dream.
In a column on Henderson in 2012, he was open about his ongoing battle with a rare, often terminal, form of cancer.

“There are signs of it getting worse,” he told me. “I have to admit the tumours are not getting any smaller. The cancer is now in my stomach, chest and lymph nodes.”

He had dropped from 184 pounds to 160 pounds.

The man who scored the winning goal in the final three games of the 1972 Summit Series against the then mighty Soviet Union was running out of both time and options.

The only goal he was focused on was trying to stay alive.

But Henderson has been known to thrive in tough circumstances, including scoring the goal of the century with just 34 seconds remaining in the final game in Moscow.

More than 41-years removed, he has proved his flare of beating the odds once again.
“It’s either chemotherapy or a clinical trial,” he said in 2012.

He chose the clinical trial and with fingers crossed went down to Bethesda, Md.

“The tumour in my stomach was the size of a grapefruit,” said Henderson, who was at the Toronto Sun’s downtown offices for an appearance on Michael Coren’s Sun News Network show, The Arena. “My spleen was double the size and the tumours were all over my body including in my armpits and my lymph nodes were swollen.”

Enter an experimental drug, called Ibrutinib, which is now being referred to as “breakthrough” therapy. “I take two little pills in the morning.”

The tumours began to shrink and now while Henderson can’t say his cancer is in remission, it is as close to that as someone with his form of the disease can ever hope for. “In my bones, they said they were 87% affected and now it’s down to 5%,” he added. “And the tumour in my stomach that was the size of the grapefruit is all but gone.” He has put all his weight back on and is back to 184 pounds.

“I just feel great,” he said. “I feel terrific but I think it’s even better for my family.” Yes, Eleanor, the kids and grandkids’ prayers have been answered.

It’s a Christmas Miracle!

“The Lord be good,” was Don Cherry’s reaction.

Henderson said the good news is also that most of the people in his clinical trial have had similar results and that one day Canadians may be able to gain access to this yet-to-be approved treatment.

He is hopeful it could mean that chemotherapy could become a thing of the past.

“When people say it’s a miracle I just say I will wait until I get to heaven and ask,” teased a smiling and upbeat Henderson.

He feels fantastic and looks even better.

“My wife joked she wants to take some of those pills because they must have Botox in them,” he said.

The Hendersons are realistic that with cancer, every day is special.

“I am told that this drug will work, they think for two years, so we don’t know what is going to happen after that.”

But what he does know is Henderson is feeling positive about enjoying Christmas with his family and even his 71st birthday on Jan. 28.

“I feel blessed because my dad died at 49,” he said. “I have never been worried because when you have hope and peace, you can handle anything.”

Henderson said he wouldn’t change a thing.

“I think having the cancer allowed me to be able to freely talk about my faith,” he said.

And, this Christmas, he is also able to reflect on another remarkable do-or-die moment he pulled out from suspected defeat and turned into victory just in the nick of time.