ASCO 2014: Dr. Kipps Discusses ROR1 and Information about a New ROR1 Monoclonal Antibody (cirmtuzumab) Trial in Relapsed and Refractory CLL (chronic lymphocytic leukemia)

Mural Detail by my son Benjamin Koffman

I am just back from a very exciting AACR (American Association for Cancer Research) Hematologic Malignancies Conference that was focused on pre-clinical research pointing the way to better therapies in the future for CLL and all blood cancers.

I will be sharing some of the most promising and clinically relevant research from that meeting in Philadelphia over the next several weeks, but first I wanted to post this timely video from ASCO earlier this year with Dr. Tom Kipps out of UCSD as there is now a chance to see how a new promising therapy using cirmtuzumab, an antibody directed at RORI will work in the real world, converting years and years of research into the first in human clinical trial.

If you haven't seen the lead up to our discussion on this brand new and very specific mAb (monoclonal antibody) targeting ROR1, then please revisit this prior post to catch the first part of our interview done in collaboration with my friend Andrew Schorr and his Patient Power team.

Remember that Dr. Kipps is a cutting edge researcher in the field of immunology and this is an immune  therapy. At the AACR meeting in Philadelphia, when I asked the father of FCR, Dr. Michael Keating out of MDACC how I might cure my own CLL, he quickly said ROR1 therapy (both MDACC and UCSD are working on CAR-T directed at ROR1- See this post with Dr. Wierda from back at ASH 2012). For many blood and cancers in general, the path to a cure means inviting an immune therapy onto the team and ROR1 is a very promising and specific target in CLL.

For more background on ROR1 by Dr. Kipps, see this, also from ASH 2012. It's a ton of long and hard bench science to bring these therapies to the bedside. Dr. Kipps has been excited about this for years and it is finally coming to fruition.

I will let Dr. Kipps tell the update of the story.



I love his push for a cure and I love his pneumonia analogy.

Now the trial for relapsed and refractory CLL patients opened recently, not too much later than the hoped for June start date mentioned at ASCO and this new ROR1 antibody, cirmtuzumab is already being used. A few patients have begun the experimental therapy, and though it is way too early to know much of value, so far so good.

Here's the link at clinical trials.gov and here is a news article on the trial.

What I like about this trial that it is an immune therapy with the promise of very little off target damage. I also like that it is so time limited- you get the 4 infusions over 8 weeks are you are done.

The downside risk. This is a Phase 1 first in human trial. Nuff said!

The dose escalation is also a potential turn off in Phase 1 trials as they are always about safety first. The hope is to find the highest dose that is not toxic called the dose limiting toxicity or DTL.

We know from our experience with the tragedies with too rapid a dose escalation with ABT-199 resulting in fatal tumor lysis syndrome (TLS) that slow and easy is the only way to go. Please see this and this and sadly this if you are not familiar with this tragic and instructive story.

The negative consequence of this emphasis on safety is the risk that those in the first few cohort may get too low or a sub-therapeutic dose.

That's why I like that this trial design. I quote from the trial site: "There is intra-patient dose escalation in the first 3 cohorts, followed by the standard 3+3 design for the next 5 cohorts."

What that means is those in the first three groups get a low dose and if they experience no problems a higher and higher dose. After that the dose is fixed for each three patient cohort.

The whole topic of Phase 1 trial design to minimize risk and maximize benefit is complicated and I am no expert, so I welcome comments from those more savvy. This is a link to a nice review article that will help if you want to dig a bit deeper.

Safety comes first and only then is drug efficacy studied more formally in later trials, but that doesn't mean there can be no measurable benefits from this kind of trial. My ibrutinib trial is sort of a phase 1 trial (1b/2) and I see no reason not to expect that this study with reveal positive results and that cirmtuzumab will eventually become an important new weapon in our arsenal to fight CLL.

For relapsed and refractory patients, admission criteria are pretty standard and there is no mention of prior transplant excluding admission to the trial.

ROR1 has been a long long time in coming.

Is it the future? It looks promising and safe in the lab and animal models, but only the clinical trials will tell us for sure.

As I have said before, the science only advances when one of patients facing a tough therapeutic decision decides that joining a clinical trial makes more sense for a host of potential reasons than standard of care. I did and it turned out to be a good bet.

When Sportswriters Cover the Cancer Beat: The Uneven Reporting of the Bob McNair CLL (chronic lymphocytic leukemia) and Skin Cancer Story

The owners of the NFL team, the Texans, Bob McNair has come out and shared his successful battle with CLL and a very aggressive squamous cell (skin) cancer.  The newspapers in Texas were full of the good news, but they didn't quite get the CLL piece right.

Please take a look at this news report:

Texans owner McNair gets clean bill of health after cancer fight

Or check out:

Texans owner McNair healthy after 10-month cancer battle

where you will read:

"McNair's remarkable recovery has included ground-breaking experimental treatment for chronic lymphocytic leukemia (CLL)…"

I want some of whatever that is.

Here is my published comment in response to the article:

Good news. While Mr. McNair's skin cancer may be curable, not so with his blood cancer, CLL. At least not yet, however, it is often controllable with therapy. Since CLL weakens the immunity, it can make skin cancers more aggressive. The message here is that anyone with CLL and many other cancers needs to be particularly careful about their sun exposure and vigilant in checking their skin for any suspicious lesions. Sadly one cancer, especially CLL, can lead to another.

Turns out a few of the sportswriters got a bit scrambled in their understanding of the management of his slow moving CLL versus his aggressive skin cancer that spread well beyond the skin requiring extensive and repeated surgeries, radiation, chemotherapy and eventually skin grafting.

The press conference with Dr. Michael Keating out of MDACC (MD Anderson Cancer Center) tells a clearer story with the full transcript at this link. Dr. Keating has a long and broad view of what we CLL patients need and I am glad he is a leader on our Team CLL. I also love the way he can generated much needed publicity about our cancer that seems to spend most of its life in the shadows, avoiding the bright lights and headlines.

The ground-breaking experimental treatment mentioned in the report was pheresis or more commonly called apheresis and its experimental use is to increase our wimpy immune response and lower our high risk of secondary cancers and their reoccurrence. 

Dr. Keating explains it at the press conference:

"You’re all aware that there’s an increased instance of melanoma that occurs because of tanning beds and things like this, but the most common forms of skin cancers are Basil Cell cancer and Squamous Cell cancer and many people like Mr. McNair have more frequent visits to their dermatologists than to the other members of their families sometimes because they keep on coming back. So the one element of Chronic Lymphocytic Leukemia or CLL, which is the most common leukemia that we see in the western world, is that there is a complex suppression of the immune system and the only non-AFDA approved activity was part of an extension of a protocol where we could take immune cells out by a process called apheresis, where you go through a machine and you take white cells out and separate the immune cells and then stimulate them up a thousand fold so they go to one-hundred-million to one-hundred-billion and give them back and rebuild the immune system to try and prevent these events from occurring."

Looks as if the transcribers may have missed a few key words and phrases.

A few reflections on what we can learn from the news.

1: Another celebrity, Bob McNair, the owner of a proud NFL team, tells the world he has CLL and skin cancer. Of course I wish he had shared the CLL news earlier, perhaps even at the time of diagnosis in order to help remove the cancer stigma and demonstrate how well he continued to live his active life for many years post diagnosis. I recognize that sharing a cancer diagnosis is a complex and very personal decision. Still I wish he had told the world when he was in the battle and not after it was at least partially over, but still I am grateful for his thoughtful and generous comments to the media about his two cancers and the treatment. I have posted extensively on this subject and received many lively comments on the decision to share the news or shut up. This link will get get you started if you wanted to revisit that topic.

2: We CLL patients are all at heightened risks for skin cancers and even the usually well behaved ones can become very nasty with our suppressed immunity. We get more cancer and the cancers we get are more aggressive. We need to use our sunscreen and our hats and have a full body skin check (and that really means full body) at least once or twice a year. See this prior post on secondary cancer risk with CLL (and CT scans).

3: MDACC and others are working hard on ways to improve our immunity. We need that. Dr. Wierda talked about his immune boosting research last year in this post. Remember that it is secondary cancer and infections that kill the majority of us that arise as a result of our weakened immunity from the disease itself and its old school chemo treatments. No point of knocking the CLL back and then dying of a secondary problem.

4: Sportswriters should stick to covering sports. Or if not, get some help and fact checking. Many otherwise fine reporters when covering cancer go for the feel good story. I guess they get tired of writing about the bad news and dirty laundry the rest of the time. That's nice, but it is not the whole picture. I promise I won't write on sports (except maybe a little about my beloved LA Kings and ice hockey) if they won't write on CLL. You don't need a medical degree to be a good medical reporter, but it sure helps. If not, then please do your research or ask for help and please tell the whole story, the good and bad.