iwCLL 2013: My Advice to Patients about their Therapy and How to Talk with Your Doctors: Shared Decision Making

It was a delight for me to be asked by Andrew Schorr on behalf of Patient Power to be interviewed in order to share the patient's perspective on how to use all the news from iwCLL 2013 in Cologne, Germany.

I particularly like the way he took the trouble to highlight some of my points with the superimposed text.

Over the next weeks, I will have many more informative interviews to post with Drs. Kipps, Kay, Furman, Hallek and others, but I thought I would first let you hear my counsel on how to best deal with your doctor appointments.

In the meantime, please let me know what you think of my suggestions and please add your own tips and advice to the communal discussion.

This is a tricky time. So many new CLL therapies on the way, but none of them are here today, except of course in clinical trials. The right approach will be different for each and every one of us. I hope this video gives some ideas on how to have the conversations that best inform our decisions.

My recommendations touch on "share decision making" or SDM, a critical and growing part of every patients' and doctors' future. It is even incentivized in the Affordable Care Act. Here one link that has a nice general discussion and video.

iwCLL 2013 Cologne, Germany

Cancer Does Not Define or Limit Us

I read this obituary notice today and it struck a note of defiance and wisdom that I wanted to share:

YAKIMA - “When you write my obituary, do not say I fought a courageous battle with cancer.”

That was the repeated demand made by Dave Clark, who was diagnosed in the 1980’s with Chronic Lymphatic Leukemia (CLL). He wasn’t joking. For once. He nevertheless fought the CLL successfully for more than 25 years.

David Bruce Clark would have completed his 68th year on Sunday, October 13, but passed away the day before on Saturday, October 12, 2013 in a Yakima hospital."

We are all much more than our cancers. When we are remembered, and more importantly, as we walk though our lives, we want to be recognized as life partners and lovers, as parents and children, as family, as friends, as co-workers, as neighbors, as congregants, as citizens, as adventurers and travelers, as helpers, as confidantes, as advisors, as advocates, as teachers, as writers and readers, as speakers and listeners, as sharers, as jokesters and musicians and artists, as the friendly stranger, as the people we are are, and not the mutant clone that wants to take us down.

As did Mr. Clark's family writing his obituary, it is OK to mention our cancer battles, especially if others can learn from our struggles, but I would agree with the late Mr. Clark and so many other patient advocates that came before us fighting their varied chronic morbid diseases, please leave out the words courageous and inspirational. It is what we must do. It is not as if we have a choice of diagnosis.

Cancer is a real and daily part of our lives.

But cancer does nor define or limit us. Never will.

Ups and Downs: Time to Under React Again

My blood count has gone from anemic to normal to anemic and back to normal all in about two weeks.

My platelets remain nice and high near 400,000, my ALC (absolute lymphocyte count) remains nice and low at about 1.0 Even at that low count, the sensitive flow cytometry done six months still showed the cancerous clone at very low levels. My T cells and the CD4/CD8 ratios are all healthy. My neutrophils are normal and my monos are as always a bit high, a potential marker of a recovering from a damaged bone marrow. But more on that story later.

My blood chemistries were all within normal limits. To all but the most astute observer of my labs, there is no hint of leukemia.

My wife says it’s the high iron in the blackstrap molasses that she uses to bake Cajun gingerbread that has cured my anemia.

I say it was lab error that caused it. Or a lab variation. Four different doctors and three different labs in two different states. I am not expecting agreement, even on the basic numbers.

After years of these ups and downs, I am finally practicing what I preach and underreacting to these blips.

My hemoglobin today at 14.2 grams is within one gram of where it has been for the last few years – somewhere in the range of 13 or 14 grams. Long gone are the days of blood counts near the top end of male normal 15-17 grams. I have to go back to August 2009, about one year post-transplant days when I topped out at 16.4.

In 2010 through 2011, while my CLL and ITP were advancing and I was clearly a sicker patient than I am now, my Hgb jumped around 12.7 and 15, but for with a few exceptions, since Dec 2010, it has been mostly hanging in the 13-14 range.

My bone marrow obviously took a hit with the chemo-immunotherapy (FCR) for the conditioning for my transplant in July 2008, but it was only one week and you’d think it would have fully recovered by now.  The lowest it ever got post transplant was an amazing resilient 10.2, to me a sign at the time that I had not been hit hard enough with chemo and ATG (see my prior posts on this topic from the weeks following transplant) to clear out my marrow of my own stem cells to make room for the donor cells to engraft. Sadly my worries turned out to be dead on and I rejected the graft and got none of the benefits or risks of the potent and potentially curative graft versus leukemia, but on the good side, I never had any graft versus host disease, and I have been never transfused. My hemoglobin had started to climb and stay above 12 grams just 60 days post transplant.

Water under the bridge. Eight years with an aggressive CLL and only one week of chemo in that time.

I think of myself as pretty lucky.

Ready to learn a little basic nonmalignant hematology? Don’t fret. It’s easy, logical, and will help you understand your own blood counts.

For a long time I was slightly macrocytic (macro or bigger than normal red blood cells or in medical talk, a greater than normal mean cell volume or MCV for short). They are many causes for that finding including low levels of vitamin B₁₂ and folate, but the one that gets my attention is a damaged marrow that can lead to a too common complication of CLL and its old school chemo treatment, a nasty cancer deceptively named myelodysplastic syndrome or MDS. CLL itself probably increases our risk of this secondary cancer. So does FCR. The macrocytosis has been less of an issue recently, but the reason may be my lowish iron (veggies have lots of iron, but it is not easily absorbed as is the iron in a juicy steak). Anemia from low iron tends to be microcytic (that’s right, micro or small red cells- you see that hematology terminology is not that difficult). So when the red cells go through the automated “Coulter” counter, some are too big and some too small, so the average is normal. Hematologists have a few ways to look for that possibility and one is even automated. They review the RDW, or the red blood cell distribution width, a freebie and part of most CBCs (complete blood counts). When all the RBCs (red blood cells) are the same size the RDW is usually in the normal range. In an anemia of mixed causes, the RDW can be high. Mine is high.

But I am not anemic, so it’s all moot. Just something to keep an eye on. Abnormal RDW and MCV are not often significant and don’t usually deserve a work-up in the absence of anemia.

I walked you through this to help you understand how a doctor thinks about these things, even when there are not “action items”. Just sniffing the air, looking for trends that might portend future dangers.

In the meantime, I under react. Know our options, keep exploring, and have a plan. Don't give up.

On an entirely different scale, for the second week in a row, I have been rerouted on American Airlines coming home. Twice, first time in Atlanta, next in Columbus, I have breezed through the TSA pre-screen security, twice I was upgraded to first class, twice I has thinking this flying ain’t so bad and twice my bubble was burst because twice, my flight was so delayed by mechanical issues that I needed an entirely different route home. Today, due to changing delays and missed connections, I was booked on a total of four different air route to various nearby airports in California as I was informed that there were absolutely no seats left on any flights to Orange County. I didn’t have a ticket home until I left the secure gate and the overworked gate agents who by their own admission were in over their head, walked out past the TSA security zone and went to the American Airline ticket counter where a smart agent nabbed me a seat home though Chicago instead of Dallas. Not first class anymore, but who cares, I get home the same day.

Had I arrived at LAX as I was at one time rescheduled at 5:10 PM on a workday, it would have added at least two hours and $40 for a “stop everywhere on the way home” shuttle, so I am very grateful to the helpful staff at the ticket counter in Columbus. 

Under react. Know our options, keep exploring, and have a plan. Don't give up.

iwCLL 2013: Dr. Jan Burger Discusses More Details on How the New Targets Therapies (TKIs) work in CLL

In the second of my three part interview with Dr. Burger out of MDACC, we get into some of the gritty details about how the new novel agents such as ibrutinib or idelalisib work in the nodes, blood and marrow.

This video interview assumes you know some of the basic of how these kinase inhibitors block homing, anchoring, and communication of our malignant B cells. For a refresher, see my earlier post from iwCLL with Dr. Burger

Here in part two of that same interview, he tackles the thornier issue of the effects of the novel small molecules in terms of clearing the marrow and also discusses what we know and don't know about their ability to directly killing the cancer cells.

We are still in the very early stages of this research, and the old cliches ring true about the more we learn, the more we realize we don't know.

Some may argue that we know that they work great and that's good enough, but until we get a better handle on how they work, what are their weaknesses and strengths, we run the risk that we may not be using them in the optimal way in terms of the combinations, sequencing and duration of therapy.

This is critical stuff, and we need to fill in the details to improve long term outcomes.

We know they are very active (that is medical talk for the fact that they work) and very well tolerated.

We know that they are kinder to the marrow.

What we don't know is how and when to best use them.

We are lucky to have so many fine doctor/scientists such as Dr. Burger interested in CLL research who can translate what they are learning in their labs to help the patients in their clinics.


More soon.

GILEAD TO STOP PHASE 3 STUDY 116 OF IDELALISIB IN CHRONIC LYMPHOCYTIC LEUKEMIA EARLY BECAUSE OF POSITIVE RISK-BENEFIT

The following press release is full of good news and positive details about the trial and Gilead's plan: the expected, and now confirmed "highly significant efficacy" of idelalisib, the access for those who progress in the trial in the placebo arm, the EAP, and the accelerated moving forward with filing in the USA and Europe.

It can only mean greater and quicker access to another powerful arrow in our quiver to fight CLL. I am pleased with every bit of it.

I only have one concern. While the comparator in this trial, rituximab, is a very commonly employed monotherapy by community hematologists for CLL, it is generally not recommended when used alone by most experts due to its low efficacy.  

Long time readers may recall that similar criticism was leveled at the phase 3 trial of bendamustine versus chlorambucil (a rarely used  treatment of limited benefit).

The FDA did accept that data versus chlorambucil and approved bendamustine.  Will they do the same with idelalisib versus rituximab?

And of course, I am dying to see the actual numbers. What was the pre-determined spread that lead to the early trial closure? We may need to wait for ASH to see that.

All in all, very good news. Next year portends to be a banner year for those of us with CLL with a potential plethora of therapeutic riches.

Here's the press release from Gilead:

GILEAD  TO  STOP  PHASE  3  STUDY  116  OF  IDELALISIB  IN  CHRONIC  LYMPHOCYTIC  LEUKEMIA  EARLY  BECAUSE  OF  POSITIVE  RISK-BENEFIT 

Foster City, CA, October 9, 2013 – Following a recommendation by an independent Data Monitoring Committee (DMC), Gilead Sciences, Inc. (Nasdaq: GILD) today announced that its Phase 3 study (Study 116) evaluating idelalisib in previously-treated chronic lymphocytic leukemia (CLL) patients who are not fit for chemotherapy will be stopped early.  This DMC recommendation is based on a predefined interim analysis showing highly statistically significant efficacy for the primary endpoint of progression-free survival in patients receiving idelalisib plus rituximab compared to those receiving rituximab alone.  The safety profile of idelalisib was acceptable and consistent with prior experience in combination with rituximab in previously treated CLL.  Gilead has informed the U.S. Food and Drug Administration (FDA) of the plan to end the study and will engage in a dialogue with the FDA regarding a regulatory filing in CLL.  Data from Study 116 will be submitted for presentation at an upcoming scientific conference. 

“Given the significant unmet medical need in CLL, particularly in this population of patients who are not fit for chemotherapy, we are pleased that idelalisib has shown a clinically meaningful benefit for patients,” said Norbert W. Bischofberger, PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer.  “This is the first Phase 3 study to report positive results for a new class of targeted therapies that inhibit B-cell receptor signaling as a major component of their mechanism of action, an important area of focus in the development of chemotherapy-free regimens in CLL and other B-cell malignancies.  We extend thanks to the investigative sites and to the other research collaborators participating in this study, as well as to the patients who volunteered, and we look forward to sharing these data with the hematology community.”  

Patients from Study 116 randomized to idelalisib will continue receiving idelalisib and patients in the control arm (placebo plus rituximab) will become eligible to receive open-label idelalisib therapy in an extension study.  Gilead is also planning an expanded access program (EAP) for patients with recurrent CLL who are not fit for chemotherapy and require treatment.

A new drug application (NDA) for idelalisib was submitted for refractory indolent non-Hodgkin’s lymphoma (iNHL) on September 11, 2013.  Gilead plans to file for regulatory approval of idelalisib in the European Union later this year. 

About Study 116

Study 116 was a randomized, double-blind, placebo-controlled, Phase 3 study evaluating the efficacy and safety of idelalisib in combination with rituximab.  The study enrolled 220 adult patients with previously treated recurrent CLL who had measureable lymphadenopathy with disease progression less than 24 months following completion of prior therapy, and who required treatment but were not fit to receive cytotoxic therapy.  Eligible patients were randomized to receive eight infusions of rituximab over 24 weeks plus either idelalisib (150 mg) or placebo taken orally twice daily continuously until disease progression or unacceptable toxicity.  Patients who progressed on Study 116 were eligible to receive active idelalisib therapy in a double-blind extension study (Study 117). 

About Idelalisib

Idelalisib is an investigational, highly selective and potent oral inhibitor of phosphoinositide 3-kinase (PI3K) delta.  PI3K delta signaling is critical for the activation, proliferation, survival and trafficking of B lymphocytes and is hyperactive in many B-cell malignancies.  Idelalisib is being developed both as a single agent and in combination with approved and investigational therapies.

In addition to a Phase 2 study in double-refractory iNHL, Gilead’s clinical development program for idelalisib includes two Phase 3 studies of idelalisib in patients with previously treated iNHL and three Phase 3 studies of idelalisib in patients with previously treated CLL.   Combination therapy with idelalisib and GS-9973, Gilead’s novel spleen tyrosine kinase (Syk) inhibitor, also is being evaluated in a Phase 2 trial of patients with relapsed or refractory CLL, iNHL and other lymphoid malignancies.

Additional information about clinical studies of idelalisib and Gilead’s other investigational cancer agents can be found at www.clinicaltrials.gov.  Idelalisib and GS-9973 are investigational products and their safety and efficacy have not yet been established.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need.  The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide.  Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility of unfavorable results from clinical trials involving idelalisib, including in combination with GS-9973 or other product candidates.  Gilead may also be unable to file for regulatory approval for idelalisib for CLL with the FDA or for CLL and iNHL in the European Union in the currently anticipated timelines.  In addition, the pending new drug application for idelalisib for iNHL may not be approved by the FDA, and if marketing approval is granted, there may be significant limitations on its use.  As a result, idelalisib may never be successfully commercialized.  Further, Gilead may make a strategic decision to discontinue development of idelalisib if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline.  These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements.  The reader is cautioned not to rely on these forward-looking statements.  These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2013, as filed with the U.S. Securities and Exchange Commission.  All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

iwCLL 2013: Dr. Jan Burger Discusses the Role of the Micro-environment in CLL: Part 1

On the first day of iwCLL 2013 in Koln, Germany, Dr. Jan Burger presented important basic science lab based research on how our CLL cells survive and grow in their protected niches and why it is so difficult to rid us of all the cancer calls, especially those hiding deep in our marrow and nodes.

His strong research along with the pioneering work of Dr. Tom Kipps and others helps us better understand the power of the new small molecules such as ibrutinib and idelalisib, and why we sometimes see the wild rise and slow fall of the absolute lymphocyte counts with treatment, particular with mono-therapy.

Without understanding the factors that influence the vulnerabilities and strengths of the evil clones that we are battling, we would never be enjoying the promise of the emerging targeted therapies. Instead. like the chatter for so many years at past ASH and iwCLL meetings, we would still be studying the best mix of chemo cocktails, admittedly often extremely effective, but coming packaged with all their collateral damage and long and short term risks.

We owe a great debt to all the bench scientist who are finding biological answers with potentially revolutionary clinical implications.

Here is the first of my three part interview with Dr. Burger from MD Anderson, Houston, Texas.

On a person note, today I saw Dr. Steve Forman, my transplant doctor from City of Hope for my twice a year follow-up. He agrees with the plan to taper the IVIG to every eight weeks and we have a plan to reduce my cyclosporin. More on all this later, after I get Dr. Byrd's sign off next week when I am back in Columbus.

iwCLL 2013: The Patient's Perspective

My friend and fellow CLLer, Andrew Schorr, asked to interview me to give  patient's perspective for his helpful website, Patient Power when we were both at the iwCLL meeting in Koln, Germany. I was happy to help.

When I attend these meetings I attend first and foremost as a patient, trying to learn what's new for myself and others with CLL, perhaps most importantly as an advocate, pushing patients' needs and priorities to anyone who will listen and who may have the influence to make a difference, as a doctor, gathering information to help my personal patients and to better understand the CLL disease state and its therapy as it relates to other similar medical conditions, as a reporter and blogger, bringing the latest news and interviews, and finally as an "on air" talking head in the video interviews.

No wonder I get tired.

Here's my interview with Andrew on my take from iwCLL. Enjoy.

News from the Infusion Center: Taking a Normal CBC for Granted

I went seven weeks between blood draws and my infusion of IVIG to coat and protect my platelets.

The CBC is usually reported back within minutes at the oncology suite.

The fact that it was all basically normal is not the news.

What is new is that I didn't ask to see it immediately. My oncologist didn't review it before walking in the room.

Both of us have grown to expect that it would be boring, and boring it was.

Hgb. which goes up and down for no reason was back to a normal 14.2.

Platelets were staying high and dry at 381,000.

My ALC was only about 1.0.

Blood chemistries were all good too except for a slightly low protein level. Uric acid was nice and low at 5.6 despite being on cyclosporin, infamous for causing accelerated gout. My LDH was stable and normal. Still waiting for my immunoglobulins.

It wasn't all that long ago that I dreaded these lab tests and waited anxiously to see if the results would land me an unplanned visit to an infusion chair or an urgent hospital admission.

How times have changed.

Thank you ibrutinib.

Now I will go eight weeks between visits for IVIG. It was needed every two weeks for years. My veins and I are truly living in gratitude.