Prevalence and Economic Burden of Chronic Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies.

This has been a banner year for developments in the treatment of CLL. In this last week of 2015 on the  CLL Society website, in our  Conference Coverage section, we share an interview from ASH 2015 with Dr. Nitin Jain where he discusses the Prevalence and Economic Burden of Chronic Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies. The success of the latest targeted therapies has increased the number of patients who are living with CLL (prevalence), but what is the economic burden of these therapies? You can view my interview with him here. Last week, we published our second quarterly newsletter, The CLL Tribune. Don't miss this special collection of research news (Dr. Byrd's interview about ACP-196) in Conference Coverage, Dr. Furman's answers to reader's questions in Ask the Doctor, basic CLL information (What is a Lymph Node?), fun facts and a wealth of wisdom and shared experiences from our fellow patients. If you are receiving this information for the first time here, you are missing out on a lot of research news, so please consider signing up to receive it here. That said, all our content is accessible whether you sign in or not If you have questions you like addressed in future newsletters, OR are interested in the results of the Q3 Reader Poll, OR are willing to answer a couple of questions in our current Reader Poll about the CLL Society website, please go to the  Ask & Tell section. Our goal is to fulfill the unmet needs of the CLL community, so we always welcome your feedback and questions. For those of you in the Charlotte or Atlanta areas, we just became aware of 2 patient meetings coming up in February: Thursday, February 4th in Charlotte starting at 5:30 PM at the Hampton Inn & Suites Charlotte (View Charlotte flyer), and Saturday, February 27th starting at 9:30 AM at the Sheraton Suites Galleria-Atlanta (View Atlanta flyer). CLL patients will be sharing their personal stories, and local CLL experts will be providing a talk on the basics of CLL. You can call 844-482-6815 to register. Complimentary breakfast and parking  are provided and you are welcome to bring a guest. I will be at both meetings with an exhibit table and will stay afterwards to meet with attendees who may be interested in participating in a support group in those areas. I look forward to meeting you there. Happy New Year! Stay strong. We are all in this together Brian Koffman

PS: I easily passed my family medicine recertification exams, despite doing little family medicine continuing education and mostly hematology for the last 10 years. Next exams in 10 more years.

This Week in CLL: (chronic lymphocytic leukemia) Chemotherapy, News of the Helios Trial, New Drug Approvals and the High Cost of Cancer Medications

The annual humongous meeting of ASCO (American Society of Clinical Oncology) 2015 in Chicago did offer those of us with CLL ( chronic lymphocytic leukemia) a few interesting abstracts and one excellent education session, but this week we wanted to share some news unrelated to ASCO on our website.

This week on the CLL Society website we are posting news and educational material that relates in one way or another to chemotherapy, alone, in combos, and in trials.

We are adding another of my treatment monologues. This time I discuss what really is chemotherapy and how does it fit into the rapidly changing treatment paradigms for CLL. Spoiler alert: The key point here is that everything is changing, very fast. You can find that link here in the treatment section of the CLL Society website.

This is a good basic primer on what chemo is and isn't. The feedback from the earlier readers has been most gratifying. Please let me know what you think.

Just to emphasize the point of change coming, on June 4, 2015 the results of the final analysis of the Phase III RESONATE-2 were released comparing ibrutinib to chlorambucil in over-65 treatment-naïve patients, excluding those patients with deletion 17p. The big news is not that ibrutinib met its primary endpoint of better progression free survival (PFS) and secondary endpoints of better overall survival (OS) and overall response rate (ORR) as we might have predicted that based on the significant difference in the usual historical efficacy of the two drugs tested in prior trials. What is important about this Phase III trial for patients is that it is an important step towards getting FDA approval of ibrutinib as frontline therapy for those of us over 65.  The official press release can be found here and my commentary will be up on the CLL Society website on Wednesday, June 10, 2015 in the news section.

Finally, we share the good news that Quebec, home to my alma mater, McGill University, and often the leader in new therapies in Canada, is the first province to approve the use of obinituzumab (O) or Gazyva in combination with that same chlorambucil (C). On June 2, 2015, there was similar approval for patients in England and Wales. These two approvals on both sides of the Atlantic were based on the trial reported in NEJM in 2014 that demonstrated the superiority of the C-O over C-R (rituximab) or C alone in frailer patients with co-morbidities. That story and links to the original research can be found in the news section on Friday, June 12, 2015.

In our ongoing emphasis to consider clinical trials when making treatment decisions, we fielded another survey to explore search functions that CLL patients would want available in a CLL-specific Clinical Trials Search Engine. We're thankful to those patients and caregivers that took the time to complete the survey at the CLL Society booth during the CLL Patient Education and Empowerment Meeting prior to the CLL Clinical Research Consortium held in San Diego, CA from April 22-23, 2015. You can view those results in the Survey Results and Clinical Trials sections of the website on Friday, also.

One last thing: If you want to share your experience about how the high cost of our cancer meds impacts your care in a way that might make a difference, please contact me to discuss how we can get the word out.

On a personal note, I am still waiting for my final lab results form OSU, so I have nothing new to share.

I don't think I can keep up the pace of 4 new posts a week, but we will try to bring you the latest news and fill in the missing gaps as best and as fast as we can.

Thanks

Stay strong

We are all in this together.

Brian Koffman

Volunteer Medical Director of the CLL Society

Blogger 

E- cancer advocate

Husband, father and grandfather

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 trials.gov, 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

BRAMPTON — 

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 .

ASH 2013: Jan Geissler & Giora Sharf Part 2 on Adherence, the High Cost of Cancer Medications, and the Importance of Clear Communication

In the second part of my interviews from ASH 2013 with two smart patient advocates in the CML world, Jan Geissler and Giora Sharf reveal the results of their important study done in conjunction with their non-profit umbrella organization, The CML Advocates Network.

Before I get too far into my analysis of the results, let me first applaud Giora and Jan for doing all the hard work in making this possible.

Not only did they recognize an unmet need, they realized that their opinions would only be respected with valid research backing them up.

Then they had to not only design, develop, and ultimately score, review, interpret, write-up and present the data, they first had to procure the funding, find the doctors willing to help, and have developed over years a strong participating network of patients ready to jump in and help.

As someone in the throes of establishing a new CLL-focused non-profit organization, let me assure you, none of this comes easily. It was earned with hard work and trust.

More news soon on how this nascent disease specific non-profit will benefit anyone touched by CLL in very focused, local, unique and practical ways while not recapitulating what is already being done so well by the LLS and LRF, two great organizations that supply excellent background disease information and much more and also provide high quality large group meetings with top flight reviews of the basics in CLL in their breakout sessions. Here is my report from the last LRF meeting. I was also privileged to be asked to volunteer to speak on self advocacy this past weekend at the LLS Blood Cancer Conference in Los Angeles. I plan to share those slides I developed here and on the LLS web site soon.

Our new non-profit will be working with smaller interactive groups and be strongly focused on the cutting edge of research. More to come. I am so excited. This will make a high difference.

But I digress.

If you haven't seen the first part of the interview or you just want to revisit it, please click here.

If you want to read their fine paper, please click here.

The first few minutes of this section of the ASH 2013 interview identifies some of the high risk markers for skipping our medications.

Later we discuss the issue of the high cost of the medication. Not surprising this is a well recognized risk. Should I eat or take my pills?  For more on this important issue, browse through my blog and take a look at this paper on cost of oral medications and adherence in CML.

Many pharmaceutical companies (see the You & I Access program as an example for ibrutinib) have generous program to help defer the cost. The LLS can be a big help, but properly constructed, well conceived, and revenue neutral oral parity laws (where the percentage of the cost borne by the patient for oral drugs and IV drugs is similar) are not only possible but are desperately needed to avoid all these welcomed but ultimately stopgap measures.

Finally, as Jan says: "Adherence is partnership." The patients, the doctors, and the patient groups getting the word out about the importance of clear communication and understandings.

Ultimately good communication is the most critical and fortunately the most malleable piece of the puzzle.

Here is the video:

Please pardon the abrupt finish. You didn't miss anything but a technical glitch.

More soon from ASH, more on adherence, and more about the new non-profit to help those of us with CLL with better support and communication.

iwCLL 2013: Dr. Byrd Discusses If and When to Stop and the Long Term Use of Ibrutinib

In this last part of my interview with Dr. Byrd from iwCLL 2013 in Koln, Germany, he speculates on the issues of long term risks of using ibrutinib, and the complex concerns about stopping the medication.

This segment's posting was delayed due to some technical issues, so please look back to the prior part one and part two to get oriented.

The updated news from ASH 2013 about the long term safety concerning ibrutinib continues to be encouraging. Most problems, including serious infections, occur most often in the first six months. The longer we take the pill, the fewer the problems.

The data on late relapses is still very thin because they are so few and far between, but it is clear that they do occur, mostly in the usual suspects, those of us who have been heavily treated or have high risk and unstable genomics such as deletion 17p or 11q.

Sadly, the Kaplan Meier curves are not longer straight lines going out towards eternal life, but they are still pretty great. Below are the ones from about six months ago from NEJM. The latest data is little changed.

KAPLAN MEIER CURVES FROM DR. BYRD'S ARTICLE IN NEJM 7/4/2013

Will they continue there downward droop? Will it accelerate? We don't know the answers yet.

Because every step down is a lost life, we are not being greedy when we want the great results to be even greater.

Dr. Byrd does make an interesting and important point about going off meds. Most relapses occurred in those who had only been medication for a short time, and without the selection pressure of ibrutinib blocking the BTK pathway, there is no survival advantage to mutating past it and therefore little likelihood that we will see that resistance develop off med. That's good news and if confirmed in clinical trials and hopefully soon, in real life experiences, could have major implications on how we dose the medication and control the cost.

Here is the video:


Since that meeting, we do have some answers to a few of the questions that were unanswered in Germany.

We know what the pills cost. About $91 each retail. About what was expected.

We are seeing some new interesting late side effects. In contrast to the minor annoyance of brittle nails, some of us are enjoying thicker, curlier and darker hair.

Maybe there is a whole new marketing opportunity for Pharmacylics and Janssen. Insurance may be hesitant to pay that kind of cost for control of cancer, but the price of vanity has no limits.

I will let you be the judge on the effects on yours truly.

Selfie from my Balcony 1/19/14

It's All Too Much: The Loss of a CLL Friend and the Approval of Ibrutinib for Mantle Cell Lymphoma

The world of CLL is unrelenting and demanding.

I tried to step away for a few days, but news, good and bad, swirled into the center of my vision, and if that didn't get my attention, it then whacked me off my seat with its wild and blunt force.

Like my six month old granddaughter saying with her fusses and her smiles, PAY ATTENTION TO ME, CLL craves to be the center of the universe.

We lost another CLL warrior today. A member of our Orange County support group, Susie Vercruse passed from complications from a stroke. This was not likely a direct CLL issue, as even with counts of a million or more lymphocytes, we don't get the dangerous hyperviscosity (the blood gets too thick) seen in other blood cancers than can lead to blood clots, but that doesn't ease the pain. I will miss her easy smile and friendly positive ways. Very sad.

And yesterday we gain a new warrior in our CLL battles. Well sorta. 

Ibrutinib or should I say now say Imbruvica was approved for relapsed and refractory mantle cell lymphoma (MCL).

This is very good news. It was as a friend in Houston said: a clean approval: No black box warnings concerning use with blood thinners (an early concern in some trials). 

The label says:

Five percent of patients with MCL had Grade 3 or higher bleeding events (subdural hematoma, gastrointestinal bleeding, and hematuria). Overall, bleeding events including bruising of any grade occurred in 48% of patients with MCL treated with 560 mg daily.

The mechanism for the bleeding events is not well understood.
Consider the benefit-risk of ibrutinib in patients requiring antiplatelet or anticoagulant therapies.
Consider the benefit-risk of withholding ibrutinib for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding 

Importantly patients only have had to fail one prior drug before they can have access to Imbruvica (get used to that name). Often new and expensive treatments are held in reserve only for those who have failed all other therapies, not just one.

Also there are no restrictions as far as I can see on how it used, alone or in combination, unlike the more limited recent approval of obinutuzumab.

MCL is much rarer than CLL, less than 3,000 cases a year in the USA, and is generally a much nastier and faster moving cancer than most CLL, with until very recently, fewer good treatment options.

Both obinutuzumab and ibrutinib could benefit a ton of patient of patients "off label", which is an ethical and legal way that many cancer and other drugs are often used.

Of course, cost will be a big issue. At an estimated more than $90 a pill for Imbruvica, the annual price tag for those of us with CLL would be just a tad under $100,000 a year. It is a full third higher in MCL as they take four 140 mg tablets daily. To their great credit, I have read that Pharmacyclics will be offering some medication free to help patients while the insurance is being worked out and will offer co-pay support for others longer term.

These days, this is the typical cost of many new cancer drugs, and is actually lower than some. Some orphan drugs used to treat very rare disorders can cost $200,000 to $400,000 a year, making ibrutinib look like a bargain.

Still 99% of us will not able to pay for that, and insurance will likely balk or in the best case scenario, take a good arm wrestle to consent to lay out that kind of cash.

We need to hope from a very broad approval for Imbruvica for CLL, speedily to minimize these issue.

It is a brave new world we are entering, and there are no easy answers. Drugs are very very expensive to get to market and for every single chemical that succeeds in making it to market, scores and scores never make it to the pharmacy. 

We can't afford it and we can't afford not to do it. 

I will post more helpful interviews real soon from iwCLL 2013 (I promise), but as John Lennon said: Life is what happens to you, while you are busy making other plans.

Non-Chemo Approaches to CLL in and out of Trials: Lenalidomide

Avoiding chemo, especially when it doesn't cure any of us with CLL/SLL, has always made good sense. My readers know my mantra of protecting our bone marrow and immune defenses for the long term battles aheads again against infections and secondary cancers.

Now with the promise of the approval of all these new agents in sight, many CLL gurus (Kipps, Keating, Byrd and others) hail the twilight of chemo as frontline treatment. Today there are even more reasons to consider non-chemo " bridge therapies" to buy us time until the magic CLL slayers are approved or there is a trial open that accepts someone with our profile (not always easy).

Besides the short term misery of the side effects in the infusion center and for the weeks that follow, why put ourselves at increased risk for secondary cancers (especially other hematological malignancies), bone marrow damage with resulting cytopenias (low blood counts), infections, and maybe even an increased risk of auto-immune issues. If we can hang on for a year or two, we can get a much less toxic therapy from our drugstore, assuming we can find a way to pay the $10,000 or more a month cost, but that's another subject. See my friend, Dr. Jeff Sharman's blog at http://www.cll-nhl.com/2013/05/how-expensive-are-new-drugs.html?m=0 for a nice discussion of that issue.

The good news is that there are already several good non-chemo options available in trials or in the clinic, for use as single agents or in combinations.

Over the next few weeks I will offer up several for your consideration.

I will start with an old friend, one of the choices that is both on the market already and available in some interesting trials.

Lenalidomide (Revlimid), an immunomodulator, is approved for multiple myeloma (MM) and some special cases of myelodysplastic syndrome (MDS). In CLL, the NCCN recommends it as 1st line therapy for those over 70 or sicker younger patients with co-morbidities. That can help you get it off label and with a little bit of effort, have your insurance to help pay for it. At an estimated $425 for each daily 10 mg tablet at Walmart that translates to more than $150,000 per year, we all need some help.

That is one real unsung advantage to a clinical trial: the trial drugs are free.

And Revlimid is also available in several promising trials for CLL. There are two in particular that are very much alike that have me excited: NCT01766583 and NCT01732861 where it is combined with a very specific BTK inhibitor (CC-292 AKA AVI-292 or AVL-292) that is behind the leader of that pack in development, ibrutinib.  More on that drug later. Both of these trials are for those with relapsed or refractory disease.  Read the details. Call the co-ordinator. Become your own expert.

If you go on to http://clinicaltrials.gov/ct2/results?term=lenalidomide+CLL&Search=Search you'll find an impressive list of 75 different trials with lenalidomide for CLLers. Many of these are closed or not recruiting, many are in combo with chemo, and many have restrictive inclusion and exclusion criteria, but take a look and you may find something that fits your need to control the CLL.

Lenalidomide has several advantages. It is an oral medication. It may work better the longer you take it. It is an IMiD that modulates the immune system, and CLL is a disease of the immune system. It doesn't damage DNA or target rapidly dividing cells as does most chemo. It make sense that it might boost the efficacy of other therapies from vaccines to rituximab (AKA R+R), steroids and more.

And as I said, it's not "chemo.

Not that it a free ride. It can suppress blood counts especially neutrophils and platelets, increase infection risk, cause a nasty and potentially dangerous tumor flare and tumor lysis syndrome, make us very sleepy, increases the risk of dangerous blood clots, should never be taken if you could get pregnant (it is closely related to thalidomide that also works in CLL) and it has been associated with more secondary cancers.

Still, today, I definitely sees many circumstances where I would take it ahead of the gold standard, FCR or the new hottie, BR.


Do your homework and check it out.

More soon on other non-chemo options including new and old TKIs and the next generation of MaBs and others.

Also part two of the Wiestner interview from ASH and more details on my recent visit to OSU.