ASH 2012: Dr. David P Steensma: Myelodysplastic Syndrome with a Focus on Secondary MDS in CLL

Dr. David Steensma is a world leader in not only basic laboratory and clinical research on MDS, but also in examining the impact that anemia has on the life of older patients.

MDS or myelodysplastic syndrome is bone marrow failure and in a minority cases, turns into an acute leukemia.

It is not an uncommon complication of CLL, both, as Dr. Steensma explains, secondary to the genetic and epigenetic changes inherent in the disease itself, and to the treatments, especially the alkylating agents that damage the DNA. In CLL, these included chlorambucil (Leukeran), cyclophosphamide (Cytoxan or the C in FCR), and bendamustine (Treanda).

This is a strong argument for younger patients to avoid those drugs known to damage the bone marrow, but Dr. Steensma offers some more subtle analysis and advice.

We also discuss the radiation risk of MDS from all those CT scans we get in clinical trials.

A good friend of mine, Wayne Bortman, is now more than two years out post transplant at MDACC for his CLL/MDS combo one-two knockout punch and he is doing great with no molecular evidence of either disease (MRD negative). And very little graft versus disease.  You can read his story at this link.

This is my last video interview from ASH 2012, but ASCO is just around the corner with more news and interviews.

Dr. Steensma clarifies and explains the risk of MDS in simple terms.

Einstein is quoted as saying: "Make things as simple as possible, but not simpler."

Dr. Steensma does exactly that.

Personal Travels

With ASCO (AmericanSociety of Clinical Oncology) and EHA (European Hematology Association) upcoming, a significant backlog of abstracts to review, promised synopsis of critical issues, important editorials, and still some videos from ASH, I am going to grab this moment at the airport in Orlando to update my crazy spring.

First the biggest most important news:

My oldest daughter gave birth this weekend to our second beautiful granddaughter. Mother and baby are doing great (if you don't consider the sleep deprivation), and I am flying to Alameda to meet the newest member of our happy growing family. I can’t wait to hold her and smell her and kiss her.

Sydney Lilah

It is being alive for moments such as this that remind me why I fought so hard to travel across the country a year ago leaving the California sunshine for an Ohio winter, uprooting my wife and myself for months, and risking a new unproven therapy to knock back my CLL and ITP. But my calculated gamble has been an unmitigated success, offering me chances to see so much more than I could have dreamed possible. And no sight will be sweeter than my new grandchild.

Now that baby has safely arrived after a very quick and natural labor and delivery, my schedule is a little more solid.

This frantic spurt of travel started at the end of April with my trip to Columbus, Ohio for my treatment. I stayed a few extra days due to scheduled CT scans, an opportunity to tour of the new hospital and Dr. Byrd’s wonderful lab (the highlight was meeting the bright and enthusiastic PHDs, MDs, and other lab staff), meals with Dr. Byrd and other friends, new and old, and an amazing Mark Rothko exhibit at the Columbus art museum.

Rothko

When back home, I had time to catch a hockey game (Go Kings Go) where the Kings beat St Louis in the Stanley Cup playoffs, before driving up to the Bay area to help my then expectant daughter and son-in-law with the toddler. That didn’t stop me from flying to Vancouver, Canada for a few wonderful days of a west coast all boys high school reunion (UTS or University of Toronto Schools) that included kayaking in Deep Cove, a gondola ride to the snow and the grizzly bears at the top of Grouse Mountain, and poignant memories.

Deep Cove, British Columbia

Now I am writing this post from a plane leaving Orlando where I attended a two day primary care medical conference.

Once back in the bay area, I will be driving back to Orange County for a day or two, then onto San Diego for one day for more learning.

Before the next week is over, and after spending time at the office, getting trained on a new EHR (electronic health record) module, and visiting the infusion lab for my life saving IVIG and a routine check-up with my local CLL doc, Dr. Sharma, I will be leaving for five nights in Chicago to cover ASCO with Andrew Schorr and Patient Power. So far Drs. Byrd and Wierda are aboard for interviews and several other familiar faces are very likely. I will also be interviewing experts on other hematological malignancies and on some solid tumors for Patient Power.

Only two days after ASCO, things get real crazy. I will be driving up to Santa Clara to lecture with Dr. Steven Coutre out of Stanford on anemia and MDS (myelodysplastic syndrome), a too common complication of CLL and its treatment. From there, just hours after I finish, I drive to SFO to fly to Stockholm for only three days to share my experience with ibrutinib from a patient’s perspective just before the EHA meeting (European Hematology Association), then rush back to the bay area the day before I leave for Chicago to see my younger daughter, just back from her delayed honeymoon in Spain and Morocco.

After another brief visit with my daughter, son-in-law and the grandkids in Alameda, the drive to SoCal gets me home in time for more doctors’ visits, clinic hours, a local CLL support group, seeing my son Ben off to Stonehenge for the summer solstice with the Druids, all followed by a two days car trip to La Jolla for more medical education conference, this time on heart failure organized by UCSD.

A week earlier, my son, Will is flying to Israel for 10 days, and I hope to arrange a meeting up with my bone marrow donor.

The next weekend I am in Baltimore for more med. ed., and the extra bonus of catching the Max Weber exhibit at the Baltimore Museum of Art.

This is the last year of my CME cycles in Canada and the USA, and I must squeeze in a lot of hours to meet my requirements. Now I have to overload my credits to catch up before the end of June. Poor planning and other priorities lead to this crisscrossing of the country.

July 3, I have been ask to lead a CLL support group for UCSD on their campus in San Diego.

In between, I have scheduling and planning teleconferences and the Stanley Cup Playoffs.

No more travel is scheduled for July until I need to be back in Columbus, Ohio again in the third week, and I am so looking forward to not leaving home for a few weeks.

This frenetic pace is not sustainable or healthy. I nap often at the hotels and on the planes. I wear an N95 mask and gobs of hand sanitizer. I treat myself to the best vegan meals I can find on the road ( which is not saying much) and I always try to see more of the town that I am visiting than the hotel lobby. In Orlando, I hiked though a lush swamp with catfish and egrets and Spanish moss that was just minutes from the silly shopping malls and alligator miniature golf courses near my hotel. No amusement parks for this traveler.

Shingle Trail, Orlando

Then I took a long nap.

I bring my comfort foods (organic raw nuts and fine Japanese green tea), meet old friends, do work that I love, and have a rare opportunity to make a small but meaningful difference in the world.

This schedule was an extraordinary confluence of opportunities and my inability to say no to spread the word about how cancer treatment is changing. I admit there is desperation to all this journeying, but I know my time is limited and I want every moment to matter.

If I was more at peace, perhaps I could sense the gravity and power found in standing still, like a mountain, like a master, but I am still a breezy soul.

Ibrutinib Research from Dr. Wiestner at the NIH

Below is the press release (PR) from the recent meeting in Washington, DC of the AACR (American Assoc. of Cancer Research) concerning the research by Dr. Wiestner's group at the NIH.

There are a number of things to keep in mind when reading the PR.

First that 29 of 53 patients were 17p del and 30 were relapsed or refractory. These were not the easiest patients to treat.

Second remember this was ibrutinib flying solo. No help from bendamustine or an antibody.

Third this is still early data. We don't know the durability of these fantastic results.

Finally , we learn that the drug is active in all lymphocyte compartments, the blood, the lymph nodes, the spleen, and the marrow.

Please take a look of this data in light of Dr. Wiestner's recent plea that we carefully reassess whether we need to continue with business as usual by insisting more is better and pushing for the "ideal chemo cocktail."

Rather I believe that these new targeted therapies demand that we fully reassess how we treat CLL and we don't just add these molecules to the existing mixes, effective as they are, but  rather we see what they can do on their own, and make slow and logical decisions about what combinations (if any) to consider. 

I like the idea of totally avoiding old school chemo if possible, but only time will tell if that is the wisest approach.

Even mixing two pathway blockers, while mechanistically appealing, is totally unknown territory.

One reason I fear that one reason that chemo or biologicals such as rituximab might get added to these trials (especially true for the very potent and active idelalisib or CAL 101 that where the high counts might linger a bit longer) is that the benign spike seen in the absolute lymphocyte count as the B lymphocyte clone cells exit their protective enclaves in the nodes and marrow and enter the blood stream where they can be counted, may last a long time and makes the early data look weak. Those raised numbers suggest the drug is not working to the uninitiated and it takes works to explain the back story. We all know that is not the case and they are in fact potent therapies, but adding chemo or a mAb solves that short term concern and speeds up the data collection. My questions are: Does it really improve outcome? Does it add unnecessary risk?

Truth is we don't know the answers. That is why we need the trials, but the reported 94% event free survival at 1 year as solo therapy is hard to improve on.

Here is the press release from AACR:

Embargoed for Release:                                                    Media Contact:

1 p.m. ET, April 8, 2013                                                      Jeremy Moore

                                                                                               (215) 446-7109

                                                                                               Jeremy.Moore@aacr.org

                                                                                               In Washington, D.C.
April 6-10, 2013:
(202) 249-4005

Ibrutinib Safe, Effective Against Untreated, Relapsed and Unresponsive Chronic Lymphocytic Leukemia

·      Ibrutinib disrupts the CLL-driving B-cell receptor signaling pathway.

·      Phase II trial showed the drug was well tolerated and effective against CLL regardless of del 17p status.

·      The drug was effective against disease in blood, lymph nodes, spleen and bone marrow.

WASHINGTON, D.C. — The novel drug ibrutinib was well tolerated and highly effective in patients with untreated, relapsed and unresponsive chronic lymphocytic leukemia (CLL), according to phase II data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“The degree of tumor reduction achieved by once-daily oral therapy was impressive,” said Adrian Wiestner, M.D., Ph.D., investigator and head of the Lymphoid Malignancies Section in the Hematology Branch at the National Heart, Lung, and Blood Institute at the National Institutes of Health (NIH) in Bethesda, Md. “We have seen patients with more than 90 percent reduction of lymph node disease within just two months.” 

Many elderly patients with CLL are unable to tolerate current aggressive standard therapies, and those with a deletion in the short arm of chromosome 17, referred to as “del 17p,” have particularly poor outcomes with chemotherapy. These two CLL patient populations that are enrolled in the NIH phase II study have the greatest need for novel treatment therapies, according to Wiestner.

Ibrutinib is a selective inhibitor of Bruton’s tyrosine kinase, a component of the B-cell receptor signaling pathway that plays a key role in the development and progression of CLL. This study confirms the single-agent antileukemia activity seen in prior phase I/II studies and extends this experience, particularly in del 17p CLL, according to Wiestner.

He and his colleagues enrolled 53 patients with CLL into two cohorts — 29 patients with del 17p and 24 patients without del 17p who were aged 65 years or older. They assigned all patients to 420 mg of ibrutinib daily and evaluated response to the drug at six months and every six months thereafter, until disease progression.

Most adverse events were mild or moderate and included diarrhea, fatigue and rash, severe events occurred in less than 13 percent of the patients.

At six months, 95 percent of patients showed at least a 50 percent reduction in lymph node disease, and all showed reduction in spleen enlargement, with a median reduction of 55 percent. In 26 patients for whom a bone marrow biopsy was done, tumor infiltration decreased by 82 percent. Absolute lymphocyte count decreased by a median of 62 percent. Using standard CLL response criteria, 52 percent of patients had a partial response. At 12 months, the estimated event-free survival rate was 94 percent.

Using blood and tissue samples of lymph nodes collected from 15 patients before and during ibrutinib treatment, Wiestner and his colleagues showed effective inhibition of B-cell receptor signaling and tumor proliferation, which was reduced by more than 80 percent, as measured by Ki67 staining.

“Ibrutinib was highly efficacious as a single agent in patients with untreated, relapsed and unresponsive CLL, irrespective of their del 17p status,” Wiestner said. “Responses appear to be durable, and the drug is effective against the disease in lymph nodes, spleen and bone marrow. This is important because existing therapies often fail to effectively eliminate cancer cells in these tissue sites. Targeted therapy for CLL is becoming a reality, and this new approach will greatly improve the lives of patients with this disease.”

This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute at the NIH.

 

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers: www.aacr.org/PressRegistration.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research

Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org. 

On a personal note, I am just back from a wonderful, meaningful high school reunion held in Vancouver, BC  though we all went to an all boys school in Toronto (UTS) three thousand miles away. I am hoping to do one of my personal reflective posts soon, but  because of the important breaking news and backlog of interviews, I have been weak on telling my CLL and life story that is happily boringly stable these days. 

Later this week I will be lecturing in Orlando, Florida. 

No rest.

ASH 2012: Dr. Adrian Wiestner: Final Thoughts

The thoughtful Dr. Wiestner of the NIH has some provocative things to say in this brief 2 minute wrap up of our interview.

He says that there may be a significant role for chemotherapy in the future for some carefully selected CLL patients.

He reminds us that these new drugs should force us to re-examine our bedrock views about cancer cocktails. They should force us to revisit all our traditional approaches.

That is a hard thing to do, but a good thing. Doctors are by nature conservative and slow to change.

But there is a sea change coming and Dr. Wiestner suggests that this is a time to really consider what  old baggage can be tossed and what we might need on this voyage.

IMPORTANT: Dr. Wiestner's trial at the NHLBI still has openings for treatment naive 17p del patients. Check out http://www.clinicaltrials.gov/ct2/show/NCT01500733?term=CLL+17p+Ibrutinib&recr=Recruiting&rank=2 . This is a great opportunity at the NIH for those who qualify and I understand a number of fellow Canadians have already enrolled.

Soon I will share his updated data on this research.

Right now, here is the second part of the ASH 2012 interview:



I still have a few surprises from ASH 2012, before I start posting from ASCO 2013 later this month.

I am happy to share that my good friend and fellow CLL survivor and patient advocate, Andrew Schorr of Patient Power and I will be combining forces to offer up several interviews on CLL and other blood and solid cancer from ASCO in Chicago.

I am looking forward to working with Andrew and his professional and pro-patient team.

I have so much I want to share here: more on non-chemo approaches, important discussions on the place of cross-overs in clinical trials, new data from the AACR meeting, what we can learn from the death and autopsy of those who didn't make it, new trials starting up and old trials closing down.

So much to share.

On a personal note, May 7th marked my one year anniversary of my taking ibrutinib. I still remember my disbelief that my nodes seemed to be shrinking in those first few days, but they were. And still are. a year later, albeit, in a less dramatic fashion.

So much has happened in this last year. My mission here and elsewhere is push that we patients can get the best possible care, and that involves more research, great doctors, and wise and brave patients.

We have all those and we sure have moved the bar forward in the last year!

Will Your Insurance Cover a Clinical Trial?

This important information is from the CLL ACOR list.

I am one lucky dude to live in California, for many reasons, including clinical trial coverage. 

A quick look at the link below suggests that coverage is pretty good in most states, and even better with private carriers compared to government plans.

Thank you Liz for sharing this:

Subject: Will Your Insurance Cover a Clinical Trial?

Whether an insurance company pays for routine care costs in a clinical trial varies by state law. In some states, only clinical trials for children are covered. In others, only costs associated with phase III trials are covered. There are many variations. Under the Affordable Care Act (Obamacare), all insurance carriers must pay for routine care in clinical trials in all states starting January 1, 2014. 

Until 2014, here is a link to current clinical trial coverage laws by state: http://bit.ly/CTStateLaws

Many drug manufacturers also offer financial assistance to make investigational (not yet FDA approved) drugs available to patients in need for off-label use by certain doctors, usually principal investigators. As Karni writes below if you have concerns about costs, ask the research coordinators on the trial. They often have their own strategies and billing tactics to help a patient get coverage and afford a trial.

Liz Hart McMillan

Director, Hope for Lymphoma

P.O. Box 5096

East Hampton, NY 11937