Is Obinutuzumab the Drug to Watch in CLL?
Is Obinutuzumab the Drug to Watch in CLL?
Dr. Cheson: There are some other antibodies out there, but nothing that is really catching fire at the moment. But there is some interest, particularly since brentuximab-vedotin, and in having antibody-drug conjugates.
Dr. Czuczman: Genentech Roche (and I have been part of those clinical trials) is looking at CD22 and the CD79B. Those are conjugated with the same agent that is conjugated with brentuximab-vedotin, which is the monomethyl auristatin E, an antitubulin toxin. There will be some updated poster studies on a CD19 antibody that is targeted with DM1, another antitubulin toxin. The antibodies that work best with respect to being able to deliver a drug or other payload to the tumor cell have to internalize when they bind to the target. So, CD19, CD22, and CD79B are all excellent potential targets.
My concern is that as we have seen with brentuximab-vedotin, patients are developing peripheral neuropathy. Physicians ask me whether it is similar to vincristine, but I do not believe so. In these cases we have to be very concerned that if we continue treating as patients develop peripheral neuropathy of grade 1 or grade 2 and beyond, that it might not be as reversible as we typically see with vincristine.
Dr. Cheson: Speaking of brentuximab-vedotin, there are some interesting data at this meeting that this anti-CD30 antibody-drug conjugate actually has caused some fatalities with pancreatitis and other severe and life-threatening episodes of pancreatic problems.
Dr. Czuczman: I haven't seen that in my practice. Have you seen it? I wonder about patient selection. The devil is always in the details. I would like to see more information about that.
Gallery of Potential New Targets
Dr. Cheson: There are some other antibodies out there, but nothing that is really catching fire at the moment. But there is some interest, particularly since brentuximab-vedotin, and in having antibody-drug conjugates.
Dr. Czuczman: Genentech Roche (and I have been part of those clinical trials) is looking at CD22 and the CD79B. Those are conjugated with the same agent that is conjugated with brentuximab-vedotin, which is the monomethyl auristatin E, an antitubulin toxin. There will be some updated poster studies on a CD19 antibody that is targeted with DM1, another antitubulin toxin. The antibodies that work best with respect to being able to deliver a drug or other payload to the tumor cell have to internalize when they bind to the target. So, CD19, CD22, and CD79B are all excellent potential targets.
My concern is that as we have seen with brentuximab-vedotin, patients are developing peripheral neuropathy. Physicians ask me whether it is similar to vincristine, but I do not believe so. In these cases we have to be very concerned that if we continue treating as patients develop peripheral neuropathy of grade 1 or grade 2 and beyond, that it might not be as reversible as we typically see with vincristine.
Dr. Cheson: Speaking of brentuximab-vedotin, there are some interesting data at this meeting that this anti-CD30 antibody-drug conjugate actually has caused some fatalities with pancreatitis and other severe and life-threatening episodes of pancreatic problems.
Dr. Czuczman: I haven't seen that in my practice. Have you seen it? I wonder about patient selection. The devil is always in the details. I would like to see more information about that.
