ASH 2013: Dr. John Pagel Discusses Radio-Immune Therapy (RIT) in Chronic Lymphocytic Leukemia (CLL)

The big buzz at the ASH annual meetings for the last few years has rightly been targeted oral therapies such as ibrutinib and idelasib and other, but one therapy that in my opinion that has received short shrift is radio-immunotherapy or RIT.

In fact, it is so rarely used that since this video was recorded in December, 2013, Bexxar (Tositumomab) was pulled from the market in February, 2014 as it was prescribed fewer than 75 times in 2012.

Zevalin (Ibritumomab Tiuxetan) is still available.

At ASH 2013, I interviewed Dr. John Pagel out of the Seattle Cancer Care Alliance (the union of the Fred Hutchinson Cancer Research Center (the Hutch), UW Medicine, and Seattle Children's) who has a very patient friendly way of explaining how these drugs work and what their role might be. Dr. Pagel is also a kind and wise transplanter and as such has extensive experience with conditioning therapies that often include different forms and dosing of radiation to prepare for the transplant and that is another reason why I wanted to hear about his updated research on this important and neglected corner of CLL research. To understand how much or little we have moved forward in the last year, please check out my interview with Dr. Pagel done a year earlier at ASH 2012. As you can read, we are still dealing with the  some of the same old issues that are slowing our progress.

RIT makes most sense to me as a mop up  or "consolidation" therapy and as I have posted before, we desperately need that. I believe RIT should be explored as a final knockout punch to our CLL when it has been decimated and only a few active cells are hiding out in our marrow and our nodes.

I suspect that this research idea won't get much traction.

Dr. Pagel is too kind when he describes why these antibodies with their toxic payload are underutilized.

True they are expensive and tricky to administer, but they are usually a one or two time treatment. 

Sounds good to me. 

The real reason they are not used as much as they could be is that oncologists can not prescribe them. You need to consult a radiation oncologist and even then, the radiation oncologist you see may not offer that option or have much experience with RIT. It requires specialized set up for its administration and management. 

So basically it is a turf issue. 

Here is a link to the abstract that Dr. Pagel presented at ASH 2013.

And here is the interview. As I said as we talked, I love his analogies.

ASH 2012: Dr. Pagel discusses transplants for CLL and the Role of Radioimmunotherapy

In the final short segment of my ASH 2012 interview with Dr. John Pagel, he discusses the approach to hematopoietic stem cell transplants (HSCT) or what were once only bone marrow marrow transplants in CLL. Now, we more often harvest the primitive blood stem cells from the peripheral blood after they have been mobilized. Much easier for the donor who doesn't need multiple bone marrow aspirations.

What Dr. Pagel talks about the real possibility of cure for some patients, especially those who go in to transplant with their disease in a deep remission.

The news is that using a drug such as Zevalin (ibritumomab tiuxetan), a radioimmunotherapy (a radiolabeled monoclonal antibody) or RIT in high doses is getting the necessary deep remissions and improving the odds of that cure. Ibritumomab is similar to rituximab in that it latches onto and destroys any and all CD 20+ B cells (cancerous or not), but it differs in that it carries a radioactive payload to those cells and thus destroys not just the cell, but its nearby homeys. This is especially helpful in shrinking bulky cancerous nodes, but can be dangerous if there are too many B cells left in the marrow as the local radiation delivered can cause lingering damage to the future home of the new donor stem cells. Still, it is a lower dose, more "surgical" way in many settings to get the radiation precisely  to the desired sites (at the cellular level) than is an external ionizing radiation source, no matter how focused. And most CLL, at least to start out, is exquisitely sensitive to radiation, although it always come back, and often comes back meaner. 

There are significant expense and turf issues in the medical world that explain why RIT is a very much underused therapy. Briefly, it is very costly per treatment, but is usually used only once or sometimes twice, so the total cost is comparable to a full course of say FCR. More tricky is the role of the doctors administrating it. It can mean transfer of care from the medical to the radiation oncologist and many doctors are loathe to give up control of their patients. We can argue that it needs the services of both a medical and radiation oncologist and their support teams of pharmacists, nurses, and technicians. More turf issues.

But I digress. RIT is a great choice if we need a transplant and we can get buy in from our doctors and insurance.

And the other news is that the mortality curve seems to plateau around 3, not 5 years. After 3 years, we stop relapsing. The CLL doesn't come back.

In other words, if we can make it three years out with no evidence of the cancer returning, we can be pretty confident that we are, dare I say it, cured.

Transplants are risky business, but are a sensible option for those who are young with aggressive disease, who may not have the time or the option to wait for one of the new magic pills. And they can absolutely be curative.

You can't say that about any other CLL therapy. At least not yet.

Here is Dr. Pagel. Enjoy.