Professor Hallek: The micro-environment in CLL(chronic lymphocytic leukemia)

Preparations are underway for the annual meeting of the American Society of Hematology, or ASH as it’s commonly referred. We’re scheduling interviews with CLL experts, scheduling meeting with current and potential supporters of the CLL Society and preparing our poster for the CLL Poster Session on Monday, December 5^th! So much to do, so little time. .

Today in the Conference Coverage section, we’ve posted an interview with Professor Michael Hallek where he discusses the role of the microenvironment in CLL and why it is an important target. You can view my article and see the interview here. http://cllsociety.org/2016/11/prof-hallek-microenvironment-cll/

Patient & Caregiver Support Meetings

November 21st @ 7:00 PM in Duarte, CA, the City of Hope CLL Support Group will be meeting. See more information here. 

Patient Education Meetings

Saturday, December 17^th - Post-ASH CLL Patient Educational Forum at City of Hope. The CLL Society, in partnership with City of Hope Medical Center and the Leukemia and Lymphoma Society will be hosting the 2^nd annual Post-ASH CLL Educational Forum at City of Hope. Dr. Tanya Siddiqi will be presenting on the latest data on Diagnosis and Frontline Treatment and Dr. Steven Rosen will present on Relapsed Disease and Novel Therapies. You can access the flyer here and pre-registration is requested. We look forward to seeing you there.

Wednesday, December 14^th at 6 PM at the Washington Marriott Georgetown in Washington DC: The Lymphoma Research Foundation will be hosting Updates on Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma as part of their Ask the Doctor series. Dr. Chaitra S. Ujjani from Georgetown University Hospital is the featured speaker. You can find out more information and register here. Dinner will be served and there is no charge to attend.

Saturday, December 10^th in Los Angeles, CA. The CLL Society will present at the conclusion of this meeting to assess interest in forming a CLL support group in the west side Los Angeles area. More details in the flyer. Access it here.

In the meantime….

Stay strong.

We are all in this together.

Brian Koffman, MD

11/21/16

http://cllsociety.org

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Stay strong.

We are all in this together.

Brian Koffman

Volunteer Medical Director, CLL Society

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 .

iwCLL 2013: Prof Hallek Discusses a Focused Role of Chemo-Immunotherapy

In this brief second part of a three part interview from iwCLL 2013, Professor Hallek precisely defines the populations that do well with chemo-immunotherapy.

It is important to keep in mind that it was only with the addition of rituximab, an anti- CD20 monoclonal antibody,  to a chemo backbone of FC, comprising together the "gold standard" therapy of FRC, that a survival advantage was first shown. Prior to the German study presented at ASH only a few years ago that proved FCR prolonged lives, no therapy had been shown to help us live a day longer.

At iwCLL 2013, we learn some very important new wrinkles on exactly who it is that benefits from FRC.

There should be no debate that the role of CIT (chemo-immonotherapy such as FCR or Bendamustine -Rituximab or BR) is shrinking. Who benefits is a shrinking pool of CLL patients with very specific demographics and FISH findings and the good news that they are mutated. This argues strongly that we should never consider FCR without first knowing our mutation status and our FISH results.

The debate is whether there is any role at all for CIT even in that select population.

The question how intense the CIT protocol should be or what is best approach may soon be moot with all the new kinase inhibitors changing everything, but at ASH 2013 a few months later we did learn that FCR has deeper longer remissions than BR but at the price of more toxicities, so the answer is as always in CLL: It depends on the patient. More on this ASH abstract later

Listen to Professor Hallek discuss who should consider CIT and who should not.

iwCLL 2013: Dr. Michael Hallek Discusses Clinical Trials in Germany versus the USA and BR versus FCR

Happy New Year.

I am in Alameda, enjoying babysitting my 7 month old and 2 1/2 year old granddaughters. Needless to say, finding a second to get any work done is tough, but the joy of being with them makes my inefficiency a small price to pay.

Today, I am returning to share additional relevant interviews from iwCLL a few months ago.

In the first part of my interview on September 11, the last day of iwCLL 2013, Professor Hallek first discusses some of the differences in clinical trials on either side of the pond.

One subject Prof. Hallek does not mention is the greater willingness of European patients to be randomized in a trial. Canadians and Americans prefer more control in deciding their therapy, and that helps explain the generally lower accrual in North American studies that have two or more randomized arms. I admit that one reason I was drawn to my trial, the official title being,  An Open-label, Phase 1b/2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, and Ofatumumab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Prolymphocytic Leukemia, was that I was assured that I would be getting PCI-32765, AKA, ibrutinib, AKA, Imbruvica. Phase 3 trials rarely offer that certainty, unless there is a cross-over and that is a big ongoing issue.

Keep in mind that the  calculus of accrual is entirely different when we are looking at the new non-chemo agents, where trials offering some of the exciting new drugs have filled at record rates.

Also don't miss the professor's definition of young.

I like it.

Next, Prof. Hallek, presages with great accuracy what was going to be announced a few months later  in at an abstract presented in New Orleans at ASH 2013, namely that BR is gentler on the marrow, but less effective than FCR. His take on what to do with that data is the real gem in our conversation. Listen to how he describes tailoring of the therapy to the individual patient.

Dr. Jeff Sharman whose interviews have and will continue to pop up here, has a nice review of the ASH data on his excellent blog.

Here is Professor Hallek, who was very busy chairing iwCLL, so I very much appreciate his time.  Sadly when my flight to New Orleans was canceled, I had to also cancel my follow-up interview at ASH, but we get the full story here and from the abstract.

Many, myself included, wonder if the whole question of BR versus FCR is moot as the era of chemo-immunotherapy may be ending in CLL. We have spent many blog posts discussing this issue, and we aren't finished yet.

Here is Professor Hallek:



More soon.

iwCLL 2013: Live from Cologne: The Opening Ceremony and Reception

Let me just say that this is going to an amazing conference. An Cologne is old worldly and charming, though vegan food will be a challenge. I am hoping I can find some time to wander the cobblestone streets and visit the Gothic cathedral. It was the tallest building in the word until the Eiffel tower was erected. And it took over 600 years to complete, started in the 1200s.

This is going to be a small but very concentrated conference on one subject only: CLL.

How concentrated?

In one row, attending the opening ceremony was Peter Hillmen, Kanti Rai, Carlos Croce, and Tom Kipps.

Talk about the who's who.

I heard about when to stop FCR (maybe sooner than 6 courses in MRD negative), epigenetics and some surprising and competing theories on clonal evolution, immune therapies, patient friendly clinical trial and this was all at the reception and opening ceremonies, which is not the scientific part of the meeting.

I got to get some sleep for a big day tomorrow.

 Michael Hallek Welcoming US to iwCLL 2013

 Professor Hallek and me

The reception (no vegan snacks, but I did enjoy a taste of the local beer, made only in Cologne)