ASCO 2014: Dr. Furman Gives us Perspective on Resistance with Ibrutinib in CLL (chronic lymphocytic leukemia)

More of My Son, Ben's Mural Work

ASCO 2014 was only a few months ago, but happily the CLL world is a fast moving place.

Since this video interview with Dr. Rick Furman of Weill Cornell, recorded and edited by Andrew Schorr and his team at Patient Power, idelasilib has been approved for CLL (see this post for discussion of its labeled indication) as predicted by Dr. Furman, and ibrutinib was approved for frontline therapy in 17p deleted patients (see this post).

YEAH to both!

Also in the intervening months, new mathematical models that consider evolution of resistant sub clones have been published by Dr. Burger out of MDACC and a high powered mathematical team headed by Dr. Natalia Komorova out of UCI. (I plan to interview Dr. Komorova as we are practically neighbors in Orange County, CA). Similar research, but this time using deep genetic analysis of the cancer's evolution over time by Dr. Cathy Wu from Dana Farber was presented at AACR 2014 Hematologic Malignancies Conference last week. (I also plan to post on her important research soon.)

The issue of ibrutinib resistance may be becoming an increasingly important issue. More and more of us are doing great with our BTK inhibited, but we still have residual disease and if you are similar to me with bad markers such as clonal diversity, 17p deletion, 11q deletion, and have a history of having been heavily pretreated (I have the first three for sure and many would say the 4th with my bone marrow transplant), then the fear of a resistant sub clone starting to act out, while still not the case for most of us even with the worst of the worst disease, is based on a growing reality of a droopy Kaplan-Meier (KM) Curve. Below are KM plots from OSU published in NATURE at the start of the year that show the downward drift in progression free and overall survival for those of us that are 17p deleted. As you can see the curves are way better than anything else out there, but they are hardly perfect.

This whole resistance issue might be largely obviated in the future by moving the new therapies up to frontline status. Dr. Furman and I both agree that is the direction we need to encourage with appropriate trials and struggles with insurers to pay for these drugs in all treatment naive patients.

Dr. Furman also mentions two exciting new BTK inhibitors, ACP-196 and ONO-4059. Click on the drugs' names to be linked to their phase 1 trials. We are just in the first chapters, but it is looking that the stories they will tell should have very happy endings. Please consider trials that offer these drugs among your treatment options.

Here is my ASCO 2014 interview with Dr. Rick Furman.



As there is a small but significant cohort of FCR patients that do great for years and years, there is a much much larger cohort of patients taking ibrutinib and other small molecules, now based on more than on more than four years of data, that should continue to do well year after year.

I am so happy for all these patients.

But I worry about the minority who won't do well, who will relapse. I am not giving up on my plea: Don't leave us stranded on 3rd base- Get us to the home plate of a cure with a follow up therapy.

We discuss obinutuzumab and ABT-199 as mop up therapies and I think those are smart choices. Maybe it will be cirmtuzumab, a new ROR1 mAB discussed in my recent post with Dr. Kipps from the very same meeting. We will only find out with clinical trials.

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.

Immunotherapy for Metastatic Melanoma

The big news out of ASCO 2013 was not about CLL, but about metastatic melanoma.

ASCO is well known to be more of a solid tumor meeting and it lived up to its reputation.

The big buzz is that now oncologists are using a new class of immune therapies that takes the brakes off the immune system so that it can aggressively attack the cancer.

Harnessing the immune system has long been an elusive goal in cancer therapy.

Until recently the best durable response rate in advanced melanoma was about 5% with a very difficult interleukin 2 protocol that made patients feel just awful.

Now it is over 70% and quite durable with simple combination of two separate immune therapy. And with a manageable side effect profile.

Moreover, the breakthrough PD- L1 antibody drugs discussed may have potential in a broad range of cancers, including blood cancers. It is important that those of us with CLL follow the developments in other tumor therapy so that we can be aware of any possible application or parallel research for our particular malignancy.

Exciting and hopeful times for those of us with cancer.

I am grateful to Andrew Schorr and the dedicated professional team at Patient Power for providing the support to do these fun interviews with these pioneering doctors. Please check out Patient Power over the next few weeks for more interviews from ASCO 2013.

Here's a link to Patient Power for the the first part of this same interview on the tremendous parallel progress in targeted therapy for advanced melanoma with a specific mutation that until recently had been well known as a fast working assassin for most victims.

Targeted therapy.

Immunotherapy.

Logical and complementary drug combinations.

This is the future not just for the treatment of melanoma, but for all of oncology.

Soon I will be posting my interviews with several CLL experts done in partnership with Patient Power.

Dr. Lynn Mara Schuchter on the Latest News on Immunotherapy for Advanced Melanoma from ASCO 2013