ASH 2013: Dr. John Pagel Discusses the Risks and Benefits of ABT-199 and TRU-016 or otlertuzumab in CLL (chronic lymphocytic leukemia)

In the final segment of my interview with Dr. Pagel from ASH 2013, he discusses ABT-199 and TRU-016 or otlertuzumab (yet another mouthful for us to poor patients to learn and pronounce).

We have heard much already about ABT-199. Here is a link to a trial reported at last year's ASCO meeting and I have an interview pending from ASH 2013 with Dr. Seymour from Australia. At ASCO later this week, there will more news on ABT-199 with a new dosing schedule to reduce the risks of tumor lysis syndrome (TLS).

TRU-016 is another under reported therapy, a potent monoclonal antibody (MAb), much like rituximab, that is as of now only available in clinical trials. In my opinion it has not received the attention it deserves. Unlike rituximab or ofatumumab or even obinutuzumab that all target CD20, TRU-016 targets CD37. But like CD20, CD37 is also found on most mature B cells, both cancerous and benign and much less so on T cells making it is a good choice for fighting CLL. That's an important difference from Campath that binds to CD52 and destroys both B and T cells. With no T  or B cells to fight infection coupled with our already wimpy immunity, we are high risk for life threatening infections. TRU-016 did not increase infection risk in this small trial.

Here is the ASCO abstract that compares bendamustine with or without TRU-016. The number were very small, but for those who received TRU-016 there was responses in the two patients with 17p mutations but not in the two with 17p deletions. As expected, there were no responses to single agent bendamustine.

And here is Dr. Pagel:



I am hoping to sneak one or two more post before I take off for ASCO 2014 later this week.

The line is drawn, the die it is cast

Let's talk CLL. A bit technical again and a revisit to some prior tropes, but it helps me rethink the road ahead.

While in Washington, Dr Kipps' nurse was kind enough to email a PDF of my bone marrow biopsy report that was full of good news. Today Dr. Kipps called to review the findings and help map out our next move.

To start, the biopsy showed nearly normal cellularity of my marrow in all three lines of cells, so despite more than five years of CLL, and a transplant, my marrow that should be full to the 41% line is full to 39%. In other words 39% of the marrow is busy making blood. Pretty good. Plus the precursors for platelets are in the right numbers; not too many (that would suggest increased destruction), and not too few (that would suggest decreased production).

The biopsy also showed the CLL to be in the nodular form, which carries a better prognosis than a diffuse interstitial pattern. The down side is that nodules may not yield their cancer cells to the aspirate, so the flow cytometry that showed 3% cancer is probably a slight underestimate. The more accurate biopsy showed 5-10% CLL.

The fact that I am CD38 negative and there is no 11 q deletion or other FISH abnormality, while good news, is likely a function of the low number of cells that are being screened and doesn't mean much.

So do my doctors agree on where to from here?

There are surprising united on at least my next step, but after that, they diverge. Still, that is more than I expected. The future is hardly certain.

Dr. Kipps is the most reserved about more rituximab now. Drs. Forman and Sharma are ready to push ahead. Kipps is more ambivalent, but ultimately said and I paraphrase, why not give it a shot. While he admits it may shrink my nodes, he does not think it will get me to MRD negative in the marrow. That is not rituximab's strong suit, but with the cyclosporin, anything is possible. R seems to make everything work better. It is the ultimate helper drug. And there is little down side. Some immune suppression, but it is easy on the marrow, and resistance seems to be not much of an issue.

So I plan to start on more Rituxan in a week or so after I return from a 1/2 day visit to Atlantic City to lecture. I am pushing for the slightly higher dose used in the German study of 500 mg/M2 x 6 weeks. The more R, the better the response!

I will continue on my cyclosporine and my IVIG.

Three months after the last dose, it will be time to bite my nails and re-stage with a repeat bone marrow biopsy and CT scan.

If I am CR, MRD negative then, probably sometime in March 2011, I can expect a long glide, a long time until I will need more treatment. If my nodes are shrunk to less than two centimeters, maybe that's the time and place for a Campath chaser to clean up the marrow if it is not already MRD negative. Kipps likes that idea, but I have my doubts due to the infection issues. If I can achieve MRD negativity, the infection risk seems to be less. Maybe any detectable residual CLL screws up the immunity even more.

If my nodes are still up then campath is out (it is lousy with any node > 2 cm), so maybe FCR or PCR a trial or lenalidamide or who knows.

Then nail biting and re-staging again.

If I am not pretty much disease free, we try something else.

Then a second transplant when I am in a deep deep remission. Excellent survival odds and a better than 50/50 shot at a cure.

That's the big picture today. It is feeling more solid, more real, but there are still way too many turns in the road to expect to not have to reroute my path to that cure a few more times.

Still I feel confident of my ultimate success.

One step at a time.