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.

ASH 2012: Dr. John M. Pagel Part 2: Present Trials and Speculations on the Near Future of Ibutinib, GS-1101, ABT-199, GA-101, TRU-016 including Combinations and the Changing Role of Transplants

I am grateful for the thoughtful, caring and careful way Dr. John Pagel tells the evolving story of CLL treatment. But I am also grateful that he is willing to speculate about what the future might hold for us CLL patients and those yet to be diagnosed.

In the follow-up to Part 1 of my interview, Dr. Pagel hypothesizes a possible future of the "game changing" emerging therapies in CLL, their paths to probable approval, logical combinations, available and coming trials, the "boots on the ground" reality of how they will be used on and off label, and the reassessing of the time and place for allogeneic transplants.

His candid observation that drugs such as ibrutinib (PCI-32765) and GS-1101(now idelalisib and formerly CAL-101) will potentially be used extensively "off label" and upfront in therapy is in my opinion, a realistic take on what is coming to the next generation of CLL patients.

When he talks about the shifting role of allogeneic transplants, we hear his wisdom and experience gained from his years of helping patients in both the pre and post imatinib (Gleevec) eras.

He informs of us the logical combinations of agents, many with no cytotoxic chemotherapy to be found anywhere in the treatment protocol, that are available right now in clinical trials and will continue to be explored.

Please be sure to view Part 1 if you haven't already. It will help with the context of this continuation of the same interview. In Part 1, there is more indepth discussion of ABT-199. In Part 2, presented below, I start by asking him about the other two big names out there ibrutinib (PCI-32765) and idelalisib (GS-1101), and he picks up from there. 

There will be a brief Part 3 soon that will deal with transplants exclusively.