Sunday, April 28, 2013

ASH 2012: Dr. Adrian Wiestner of the NIH (NHLBI) on his Research Findings with Ibrutinib and Reflections on the Changing Therapy for CLL

Even though the Annual Meeting of the American Society of Clinical Oncologists or ASCO is only a month away, there is still much valuable information to share from the ASH 2012 Annual Meeting six months ago and there is no one better than Dr. Adrian Wiestner from the NIH (NHLBI) to teach us.

At the upcoming ASCO meeting, there will undoubtedly be fresh reports that improve our understanding of the underlying biology and treatment of chronic lymphocytic leukemia (CLL), but let us pause to remember just how quickly the treatment landscape is changing by taking some parting glances at the data from ASH 2012.

Let me explain what I understand to be the main differences between ASCO and ASH, two giant cancer conferences vying to attract the best groundbreaking research papers and the oncology crowds that follow them.

I have been attending the annual meetings of the American Society of Hematology (ASH) for many years. Approximately 15,000 hematologists from around the world meet every December in major American cities offering a convention center big enough to handle the crowds and interesting enough diversions for the docs and their families. Last year it convened in Atlanta; this year we’ll converge on the Big Easy.

ASH emphasizes an exhausting array of exciting basic laboratory research, in addition to the clinical trial data and many practical “how to treat” symposia.

This upcoming conference will be my first ASCO meeting.

ASCO, as the name suggests, is more clinical in its orientation and much bigger. Gimongous! At twice the size of ASH, the 30,000 attendees annually trek to Chicago where the McCormick Place Convention Center has room for them all. Wear comfortable shoes because there will be a lot of walking. Plan your days carefully and pick a track on breast cancer or brain tumors and be prepared to run from room to room.

My chief interest of course remains my personal torch, CLL; but I also plan to expand my reporting on other B-cell lymphomas specifically, and hematologic cancers in general, with some important diversions to cover the latest on a few common solid tumors.

What I don’t yet know is how much will be revealed at the ASCO meeting about the emerging basic lab science related to CLL, especially the importance of clonal evolution and the critical role of the microenvironment.

What I do anticipate is more mature clinical trial data on ibrutinib (PCI-32765), idelalisib (CAL-101), ABT-199, and GA-101 and also a host of preliminary studies on other TKIs (tyrosine kinase inhibitors or small molecules, usually oral meds, that block pro-survival pathways in cancer) and the new mAbs (monoclonal antibodies trying to improve on rituximab) that are in early development.

Concerning the leading TKIs, here are my questions:

What is the durability of the response? 

What have we learned about the significance of the almost universal finding of a low level of residual disease with these new TKIs?

What do we know about the longer term adverse event profiles, including the risk of Richter’s Transformation, secondary cancers, immune function, and infections?

Maybe most importantly, what have we have learned from the few CLLers who have relapsed? Who are they? What are the risk factors? Is there anything we can do to improve the already good odds?

Concerning the newer dugs and the mAbs, I want to hear which pathways offer us the best promise of a lengthy trouble-free survival.

I posed some of these same questions last December at ASH 2012 and there is no one better to teach us than the thoughtful Dr. Adrian Wiestner from the NIH.

His deep, inventive, commercial free, and government-sponsored research includes a focus on non-chemo approaches to CLL.

Ibrutinib specifically, and kinase inhibitors in general, all induce dramatic responses in CLL with a very favorable adverse event profile. That is great news for all with CLL, but especially those with difficult to treat disease, such as those of us with 17p del or refractory disease.

In the first part of my ASH 2012 interview, Dr. Wiestner discusses some of what is known and what questions he is hoping to answer. You get a sense of why he is so exited about these new lines of therapy.

And he correctly predicted the rapid enrollment in the phase III RESONATE trials comparing ofatumumab and ibrutinib. It just closed accrual with its 350 subjects, every one of whom deserves our gratitude.

Enjoy Dr. Wiestner.

On a personal note, I remain with my mild iron deficient anemia. Maybe that explains my increased fatigue. The rest of my lab remains super. I am off to OSU today for yet more lab, more ibrutinib, and radiotherapy also known as CT scans. Only kidding, but CTs every 3 months is excessive!

The treat on this trip besides the Mark Rothko exhibit at the Art Museum in Columbus and seeing old friends and smelling the spring flowers at the Metro Parks, is that I get to tour Dr. Byrd’s lab and the new cancer hospital under construction (again sensible shoes and this time I will need a hard hat), meet some other CLLers, and best of all, have a chance to break bread with Drs. Byrd and Flynn.

More soon from Dr. Wiestner from ASH 2012 and prep for ASCO 2013.

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