A roundtable discussion, moderated by Thomas Martin, MD, of the UCSF Helen Diller Family Comprehensive Cancer Center, focused on CAR T-cell therapy considerations in the treatment of multiple myeloma, including data on approved CAR-T options and a look at the pipeline. Dr. Martin was joined by a panel that included Sagar Lonial, MD, FACP; Peter Voorhees, MD; and Shambavi Richard, MD.
In the next segment of the roundtable series, the panel discusses allogeneic CAR T-cell therapy and how it stacks up against autologous options.
Dr. Martin: I’m curious of what your experiences have been, Peter and Shambavi, in terms of allogeneic chimeric antigen receptors (CARs). Have you guys done any allogeneic CARs or do you think there’s an ideal space for the allogeneic CAR T-cell therapeutics?
Dr. Voorhees: I don’t have personal experience with the allogeneic CAR T-cell products, but certainly in the relapsed/refractory, more heavily pretreated patient population, I think that’s the niche where they make the most sense. As Sagar pointed out, the starting product in our myeloma patients may be compromised in a number of different ways. I also think that these patients are very difficult with regard to controlling their disease in the lead up to their apheresis, as well as during the period of manufacturing for the autologous CAR T-cell therapy. In the relapsed/refractory scenario, having access to something that you can give right away has a lot of merit.
Dr. Richard: We have the ALLO-715 trial at our institution. We’ve done a few of these patients. I completely agree with what Sagar was saying earlier in terms of seeing those, first of all, quite tolerable, great vein-to-vein time, essentially off-the-shelf product. It’s really not even a vein to vein, but essentially we are able to turn around and give the drug very quickly after enrollment. That’s a pro. Pretty tolerable and able to handle; the response rates are pretty comparable as well. But I think the issue is in the duration of response and so still got to work on that.
The other big thing is with the anti-CD52, because that does increase the infection risk considerably. We’ve seen one of our few patients that we have done on this trial who literally got hit with shingles and then cytomegalovirus, it was just back-to-back viral infections. This is well known from this anti-CD52 from previous studies in CLL and other disease entities. But I think these are some of the things to kind of pay attention to just to improve the persistence and to avoid graft rejection or the product rejection, we are having to intensify this lymphodepletion therapy and that is not without its cost.
Dr. Martin: Yeah, completely agree. The more intense lymphodepletion certainly lines them up unfortunately for more infection and this is being used in a more, I would say, challenging patient population, even though all these patients are very challenging because they’re multiply relapsed, but these are the ones because it’s off the shelf, these are the ones that potentially could have rapidly progressive disease and now we’re trying this therapy with them. The response rates may actually be lower with allogeneic CARs just because of the patient population versus what we do with autologous CARs.