Wednesday, April 30, 2014

ASH 2013: Dr. Furman: Idelalisib in Fragile CLL (Chronic LymphocyticLeukemia) Patients

I am going to be busy posting several videos from ASH 2013 because some of the new data that I will be discussing from ASCO 2014, May 30-June 3 in Chicago will be the longer term follow-up data from the same studies.

Today is a short interview with Dr. Furman on his late breaking abstract presented at ASH 2013.

Dr. Furman was the lead investigator and author in this important NEJM article, arguably the world's  most prestigious medical journal. Dr. Furman, out of Cornell Weil, was deeply involved in the first in human trials of both ibrutinib and idelalisib. This important post from only one year earlier at ASH 2012 seems like ancient history as we have learned so much more about these game changing treatments. Worth reviewing to see just how far we have come in such a short time.

The study that we are discussing in the video (click here for the abstract) is pretty interesting for many reasons.

The first is the the particular population that was targeted.

I have blogged in the past about how we determine whom is fragile and whom is elderly. The CIRS score is one way to quantitate how sick we are besides having the obvious problem of CLL that needs treatment.

The group that was studied here was those of us who were likely not be able to tolerate a full course of chemo-immunotherapy due to our co-mordid conditions.

Turns out this group was also a tough group to treat too. 80% were unmutated and 45% had the dreaded deletion at 17p.  

This combo of fragile and tough to treat patients is a group that until very recently had few options and so I commend the researchers for looking to these neglected group.

The next interesting aspect of this trial was that it was placebo controlled. One arm was just single agent rituximab and isn't rituximab alone a pretty wimpy comparator? Dr. Sharman and I discussed this in some depth in a prior post. I recommend you review it. That way you will have the opportunity to hear from an important CLL researcher and also from the lead investigator about this same study.

And it did build in from the get-go a cross-over for those who progressed which for me mitigates much of the ethical problems with the trial design issue.

The adverse event profile is encouraging. One case of Richter's. As CLL is being better controlled, Richter's is becoming too often the cancer's escape route

Next, take a look at the data itself. It was very very impressive.

Finally, Dr. Furman gives his perspective on how this study and the other news out of ASH 2013 is influencing therapy choices for not just the fragile CLL patient, but for all of us.

Dr. Furman has been a pioneer and visionary in moving away from chemo based therapies of CLL. I am grateful for what he has done and even more so for the brave patients that have entered his and  others' clinical trials, especially the more risky early phase 1 trials. Without their courage, there would be no progress.

Much more to come soon.

I just learned that I will be lecturing on CLL to primary care providers at the Baltimore Convention Center on June 28. This is an introductory lecture with videos from interviews with Drs. Kipps and Wiestner and others. I'll be there June 26-29 and leave from there for Columbus, OH for every 84 day visit to Dr. Byrd in my CLL trial at OSU. Talk about having skin in the game. Please come, hear the lecture and visit. The day before I will be also speaking on gout and CAM. See this link below for my US lecture "tour"  schedule. This will be for CME, continuing medical education, that is intended mostly family doctors but many sophisticated patients find the presentations very helpful. And it's free. I would love if you could drop by and say hello.

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Friday, April 25, 2014

Another CLL (Chronic lymphocytic leukemia) Patient Dies Disease Free from Complications of Her Treatment

I lost another friend to CLL: a kind and powerful woman who so loved her life filled with friends and strong family support and love. She was an important and passionate member of our local support group.

Too young, too alive to be gone so soon.

She was treated at the end at one of the world's best CLL centers, but that transfer of care from a community oncologist might have come too late.

When she passed on, her CLL was nowhere to be found, but her uncontrollable GVHD (graft versus host disease) from her transplant (her sister was the donor) killed her. GVHD can be so unpredictable and so relentless.

Yet another death by treatment.

Transplant is a very blunt tool with huge collateral damage, but when the disease is on the march again and has wised up from former chemotherapy so that it can no longer be lulled back to sleep with the usual drug combos, transplant may be the only option left that offers us another chance. I am glad it's available. It can be a life saver. Or not. Remember that I opted for one for myself almost 6 years ago. That's how this whole blog started.

The issue, however, is not knocking back the CLL. That we can do most of the time. The issue is healing the patient. That is where we fall short.

That is why I am pushing for new therapies.

That is why I am looking at preserving our immunity and our marrow.

That is why we need research to rebuild our damaged B and T cells.

The pain of these losses motivates what I do here on the blog and out there in the community. Most of the time, I feel so lucky to be able to do blog and share my story and ideas and interviews.

But sometimes, like today, it just reminds me of how vulnerable that we all are and how raw are our  wounds .

Right now, once again, I will just want to stop and stoop my head and say a prayer for her family.

I am so sad.

I hate this cancer.

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Sunday, April 20, 2014

My Chronic Lymphocytic Leukemia (CLL): More Good News


I still have CLL, but less of it.

It's in remission and it's actively retreating, but I still have residual disease.

Today I learned that my flow cytometry showed that I have a few cancer cells floating in my blood stream.

Here's how I know.

Essentially all B cells, good or bad, cancerous or benign, have a CD19 marker but are not supposed to have the CD5+ marker on their surface.  That's usually found only on T cells. Those that have both are my abnormal CLL cancer cells.

Flow cytometry which looks very deeply at thousands of cells was able to find only 28 of such cells per 10,000 cells. That means only 0.28% of my lymphocytes are clonal.

Let's do the math. I am a little shaky on my assumptions here, so please correct me if I'm wrong. Of every 10,000 lymphocytes that I have, only 28 are my CLL clone. That is an amount a microscope could never find, but the flow cytometry lasers can spot easily. If my nodes and bone marrow were clean (not likely but I can hope), I would be in a complete remission (CR), but minimal residual disease or MRD+. How important it is to be MRD- in the era of TKIs is a matter of debate.With FCR, it was very important in terms of prognosis.

There are 1,400 lymphocytes per millionth of each liter of my blood and of course there are a million microliters in every liter. We we all have about 5.6 liters of blood, so 1,400 x 1,000,000 x 5.6 x 0.028 = about 22,000,000 cancer cells lolling around in my blood stream. Sounds like a lot, but it's nothing.

Those millions and millions of peripheral white blood cells are not even the one that are proliferating. That's done mostly in the nodes, so my nodes are pumping out less cancer now. I know that because in October, the same count was 47. That's a 43% drop in the last 6 months, suggesting my CLL is still responding nicely to the ibrutinib.

After nearly two years, it is still working its magic inhibiting the B cell communication pathways needed to survive and reproduce.

That's truly great news.

Reassuring news.

Quite remarkable if we stop and think about it. Almost two years out and this gentle giant of a therapy is still dropping my leukemic cell count.

To get some perspective on my results, compared to my measly 220,000,00 cells in my entire blood stream, some of my friends with active disease can have half a million lymphocytes or more in each and every  millionth of a liter of blood and nearly everyone of those is a part of the evil clone's posse. 500,000 x 1,000,000 x 5.6 is a big number. The counts of almost anyone with active disease is several orders of magnitude greater than mine. My count of CD19/CD5+ cells is trivial in comparison.

The other good news is that my overall T cell count is climbing with appropriate CD4/CD8 ratios. This could mean my ability to fight off infections is improving and more importantly my bone marrow and the rest of my immune system is healing.

My CLL has always been more nodal, hidden in my belly, so the CT scan at the end of June will be critical, but this is a positive harbinger. Makes sense that if I harbored any significantly growing nodes that were resisting the ibrutinib, they would be pumping more cancer out into the blood and the exact opposite is happening. But the relationship between the size of the nodes and the CLL count in the blood is not always so tight. Still it is good news.

I will be posting more videos from ASH soon and am preparing to attend ASCO in Chicago at the end of May.

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Wednesday, April 16, 2014

CLL (chronic lymphocytic leukemia) Treatment Internationally: We Can't Always Get What We Want

Below is an article from the Brampton Guardian.

This unfortunate CLL patient can't even get bendamustine and rituximab in Ontario, Canada, let alone ibrutinib or idelalisib or ABT-199 or obinutizumab. OHIP, the provincial insurance won't pay for any of it.

Here in the USA, she would automatically qualify for ibrutinib as as second line therapy or she could get her BR or enter a trial or a host of other choices. Not so in Canada.

I am so lucky to be able to have received ibrutinib in a clinical trial long before it was approved.

Others, mostly those wanting a non-chemo first line therapy, have been less fortunate. Still on clinical, a quick look found eight open trials for untreated CLL patients with either ABT-199 or ibrutinib or idelalisib or obinutuzumab. And there are many more options using other very promising TKIs and mAbs in development. It's true that you can't be assured that you can get ibrutinib by prescription for frontline treatment, but at least most American untreated patients have many fine options with or without chemo.

When I advocate for more research on the the multi-drug non -chemo treatments for those of us such as myself not in CR after two years of ibrutinib, it is not meant at the expense of those needing other therapies or better access.

I want to see improved access for all of us. One way that might be possible is by following a path such a Professor Hallek outlined at ASH 2013 to limit the duration of therapy and thus control cost. I would just leave out or at least severely restrict the chemo piece of his protocol. His full article is available and well worth reading. It is a thoughtful discussion and one vision of the possible future of CLL treatment.

This is all new territory and we need the trials on untreated patients and we need the trials on relapsed patients and we need the trials on patients not in CR.

Truth is we are barely at the break of dawn of this new era of treatment and we need so many studies to help guide us. We are making this up as we go along.

What we also need to remember is that we are are all in this together and none of us, myself included, should wish for an option that limits another's choices. At least in the USA, we are not at that point.

Canada may be a different story. There is a petition at the end of the attached article. Her denial of care seems cruel, unjust, unscientific, and just plain dumb to me.

I understand that nearly all cancer treatment is expensive. I understand society must make tough choices about how to allocate limited resources. But making choices based solely on arbitrary protocols and short term dollars signs is not good policy, especially when it clearly stands against both the best evidence based medicine and the specific clinical circumstances of the patient.

Truth is that ibrutinib might be a smarter choice than BR for this patient after relapsing only four years post FR. Truth is we learn nothing in this article about the state of her marrow. Can it handle more chemo? We don't even know her FISH. If she is 17p deleted, BR could be a dangerous waste of time and resources, and might leave her worse off than before the therapy.

In the end with CLL, one has to chose which battles to fight. Anne and her oncologist have made their choice and are pushing for BR, so I am assuming they are on their game and have done their due diligence.

Yesterday, I heard from patients in Turkey and China looking in vain for novel therapies. I quote from the latter email discussing ibrutinib: Indeed the medicine cost is too high, and even if it's approved to be imported to China, the market price in China would be still higher (with extremely high custom rate), and yet any imported medicine is out of the range of medical insurance in China.

It's tough for my friends in Europe too. NICE that regulates new drugs in the EU can be very price sensitive and there seems to be be fewer non-chemo trials.

I know how spoiled I am living in the USA. I know how lucky I am to have nabbed a spot in my trial.

I wish everyone everywhere had access to what they needed to be well.

After all, we are all in this together. 

But there is only one of me and I am spread pretty thin already, so I narrow my focus, and try to make sure that at least those of us in North America get the best possible and smartest treatments out there.

The LLS is doing important work on improving access through its patient advocacy and other efforts. They deserves our support. See the photo below.

Brampton woman denied OHIP coverage for life-saving cancer drugs

Brampton Guardian


Anne Mitchell is fighting an uphill battle.
After four years in remission, the 67-year-old mother of two is gearing up for her second battle with Chronic Lymphocytic Leukemia.
But dealing with cancer isn’t the only obstacle the Brampton woman must overcome. The real challenge now — apart from fighting the illness — is coming up with the money to pay for life-saving drugs.
“My mother can’t receive chemotherapy drugs, purely for bureaucratic reasons,” said Mitchell’s daughter Eleanor Elliott, who has launched on an online petition in a bid to pressure the provincial government to dole out the $52,000 her mother needs for the chemotherapy drugs Bendamustine and Rituximab.
The drugs are covered by OHIP.
Mitchell is being denied coverage based on what family members say is a technicality. Bendamustine is covered for first-time chemotherapy treatments.
But, since Mitchell has undergone chemo before, the drug isn’t covered by OHIP. The other drug, Rituximab, is approved for second line use, but only in tandem with Fludarabine — a drug that Mitchell can’t take because she suffered an extreme, adverse reaction to it during her first bout with chemotherapy.
“The drugs that my mother’s oncologist prescribed are funded by the government. However, in my mother’s case, they have denied her funding,” Elliott said. “If a drug is approved for funding, how can you deny a Canadian citizen access to that drug? How is this possible in our great country that prides itself on universal healthcare?”
In October 2010, doctors treated Mitchell’s cancer with Fludarabine and Rituximab, two very powerful chemotherapy drugs.
Mitchell, who has lived in Bramalea for nearly 40 years, received got through two treatments before the regime was abruptly stopped because of her negative reaction to Fludarabine.
Mitchell was hospitalized for weeks with a severe lung infection that nearly killed her.
Despite that setback, her cancer went into remission and Mitchell and husband John, 68, were looking forward to better days.

But the cancer has returned and doctors believe Mitchell’s fighting chances are good if treated with a combination of Bendamustine and Rituximab.
However, the hefty price tag on those drugs now stands in Mitchell’s way.
Mitchell’s latest chemo treatment was to start April 7. Shortly after arriving in the oncology department at Brampton Civic Hospital, she received news that the $8,700 for the Bendamustine and Rituximab would have to come out of her own pocket.
“I felt complete and utter shock,” said an emotional Mitchell, describing her reaction when told OHIP denied her payment.
Mitchell used a credit card to cover the $4,500 cost for the first round of Bendamustine. She needs six treatments in total and can’t afford the cost.
Elliott said the hospital administered the Rituximab at no charge and has put through an appeal to Ontario’s health ministry for the $4,200.
“I sat in shock as my mother had to pull out a credit card to pay for her treatment,” said Elliott, who is concerned that her parents will be forced to spend their retirement savings on cancer treatments.
With her mother facing an uphill fight, Elliott has taken to social media for support. Her online petition has so far garnered more than 600 signatures, She plans to present the petition to provincial health officials.
Bramalea MPP Jagmeet Singh has offered his support in the form of a letter sent to Ontario Health Minister Deborah Matthews appealing for help
Meanwhile, Elliott has also reached out to the manufacturer of Bendamustine.
According to Elliott, Lundbeck Canada has agreed to cover 20 per cent of the cost of the Bendamustine, but the family will have to pay the cost up front and then apply for a rebate.
But, as Elliott noted, that works out to be just about 10 per cent of the total cost of her mother’s required treatment.
Elliott argues that her mother wasn’t able to complete her first round of chemotherapy and therefore should still be considered a first-time patient.
Falling under the category of first-time chemotherapy patient would make her eligible for the Bendamustine. Elliott also wants Ontario to waive the requirement that OHIP will only cover Rituximab if taken with Fludarabine.
She argues that approved chemotherapy drugs be approved “without discrimination and without bureaucratic intervention that could cost Canadians, like her mother, their lives.”
To view the online petition click here .

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Monday, April 14, 2014

Personal Update on my CLL (Chronic Lymphocytic Leukemia): The Good News

It's been a while since I posted on my personal medical news.

Today in Columbus, it was all good. CBC was happily and boringly normal. My Hgb still shows that I am no longer anemic. My ALC (lymphocytes) is 1.4 which is actually a bit high for me, but certainly a comforting level.

My ANC (neutrophils) was healthy. My platelets are a bit higher than normal again, but that is to be expected due my splenectomy. The spleen gleans the aging and decrepit platelets, so counts are higher when it's missing. I will take high platelets any day over the terrors of single digit counts when my ITP was raging. By the way, the accepted wisdom is that the high platelets associated with a splenectomy do not increase the risk of a blood clot, but ironically ITP which ravages the platelets does. You can both hemorrhage and thrombose with the same disease. Seems inflammation is the enemy. I refer you to the 19th century wisdom of Virchow's triad, a trusted nugget carried in the brain of all medical students. 

More on this particular topic soon with some personal revelations, but that is for another post.

My blood chemistries show my liver and kidneys are happy and healthy. The advantages of a vegan lifestyle.

Dr. Byrd would not agree to skipping my next CT scan in three months. The very few late relapses on ibrutinib that he has seen after 24 months (my two year anniversary of living with the TKI magic of ibrutinib aboard will be at 9:30 AM EST on May 7, 2014) are often subtle and begin in the nodes. With my pesky abdominal nodes, that does seem prudent despite my aversion to more diagnostic "radiation therapy". Getting the scan at the newer CT at OSU's Martha Morehouse may cut the rads by as much 60%.

Most relapses occur between 12 and 24 months, so my period of higher risk is thankfully coming to an end. 

Still my clonal instability and my small subclone of 17p deleted cells keeps me forever on alert.

What we really need is a trial for the many patients such as myself that are doing very well on ibrutinib, but are not in a complete remission (CR). How about adding in a PI3K inhibitor such as idelalisib or one of the newer ones following in its footsteps. Hit the cancer clone on two pathways at once. A pincer move. A classic chemotherapy technique, but instead on chemo, we box off the cancer with focused therapies. Next add a potent third generation monoclonal antibody (mAb) such as obinutuzumab once the rascally clonal B cells have been released from the nodes and marrow out into the open spaces of the blood stream where they are easy picking for the antibody. Finally, we add something to mess with Bcl-2, say ABT-199. All this done in a carefully orchestrated and timed dance to maximize efficacy and dodge tumor lysis (TLS) by adding the ABT-199 as the final coup de grâce to make sure the beast will never rise again, but also when the tumor load is low so the risk of TLS is mitigated.

You can't get to cure without first passing by CR and MRD (minimal residual disease) negative.

For me, this is not a theoretical discussion. This is my blood and marrow and proliferative centers in my node that are at stake.

The same applies to many others that are in similar circumstances with ibrutinib and other TKIs.

It may even make long term financial sense in that it may also be a way to limit the duration of therapy with this initial treatment intensification, but with a predicted end of treatment baked into the plan.

I don't want to wait until it's too late so I am hoping such a trial may come to pass, speedily, in my time.  

These and similar concepts are beginning to percolate out there.

What do you think?

I am wondering about bouncing such a plan off the powers that could make it happen. Right now it is a small population that would qualify for such a trial, but our numbers are growing fast.

Please give me your feedback.

"You may say I'm a dreamer, but I am not the only one."

More news, personal and general soon.

I wish a meaningful Passover to all my Jewish friends. May we all leave our personal Pharaohs behind and cross dry shod into the promised land.

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Friday, April 11, 2014

ASH 2013: Dr. Claire Dearden Discusses CLL Treatment in the Elderly

One of the nicest doctors in the world of CLL is the English hematologist or should I say haemotologist, Dr. Claire Dearden of the Royal Marsden in London.

At ASH 2013, Dr. Dearden and I reviewed the new studies on the treatment of the most common group in CLL but the most underrepresented in clinical research, namely the elderly patients.

At ASH 2013, several papers made significant progress addressing this gap and that is what we discussed.

We can hear echoes of my discussions with Dr. Jeff Sharman in a recent post on the trial of idelalisib with and without rituximab. In that interview, we focused on the ethics of that placebo controlled trial.

We may also recall that Dr. Jennifer Brown and I discussed in another ASH 2013 post the very exciting trial of chlorambucil alone, with rituximab or with obinutuzumab that Dr. Dearden mentioned.

There was also important information of relevance for this population group in the long awaited study comparing FCR versus BR. For another thoughtful discussion on this, check out Dr. Jeff Sharman's excellent blog post. Here is a link to the actual study data presented at ASH. In the over 65 group, there was no progression free survival (PFS) advantage for FCR over BR despite the former's greater toxicity, especially in this age group. This is news we can use.

But before we get started in deconstructing the data, one of the first issues we must address is exactly how to define old. Turns out there is much research on looking at the biological versus chronological age. The CIRS scale is commonly used to look at co-morbidities, but as Tait Shanafelt out of Mayo Clinic pointed out in his important educational paper at ASH on this topic, we need to look at quality of life, life expectancy (approximately 20 years for those us 65 years old), and frailty. It's not just calendar years.

This is the biggest reason I push for a healthy lifestyle. It is not that a plant based diet and regular exercise will cure our cancer, but we are sure to do better if we have fewer co-morbidities, and living healthy helps with that. We don't need to add diabetes or renal disease or heart trouble to our list of woes that come pre-packaged with CLL. More problems unrelated to CLL lead to more problems related to the CLL.

Here is the interview with Dr. Dearden.

The news is good. Options are improving. I am not thrilled with chlorambucil as the backbone of the therapy, an admittedly gentler but still old school alkylating agent in the same class as bendamustine or cyclophosphamide (cytoxan or the C in FCR) or mustard gas. Just because it's a pill, doesn't mean that it's safe. Moreover, I am sure that the heavy lifting in this trial was done by the immunotherapy agents, rituximab and especially obinutuzumab. But chlorambucil is cheap (as little as $1.50 a day for the lowest dose) and easy to take.  It is very popular in Europe and was a favorite of the late great Dr. Hamblin.

One more point.

As we hear from the end of our discussion, the choices are complex and nuanced. As I have said before and as has been proven in a study out of Mayo, we do better with a CLL expert as part of our team guiding us through our therapeutic decisions.

Finally, Dr. Dearden reminds us of the many unanswered questions and that's why we need more research.

I have been traveling and meeting with fellow CLL friends, but I am back and trying to catch up on a backlog of videos and personal stories and adventures to share.

Stay tuned. Posting should be more frequent over the next month.

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