Nuances of Using Frontline Daratumumab for Myeloma

Transcript: Amrita Krishnan, MD: When we talk about cost, well, plerixafor, I think it was almost 4 times. And when people need it, that’s not an inexpensive addition to your regimen. The last thing is I’m very torn with the infection risk with adding DARA [daratumumab]. It’s a great regimen and we put a lot of patients on the GRIFFIN trial. There was a lot of respiratory infections. We end up giving a lot of IVIG [intravenous immunoglobulin], and then I mentioned that at one of the ASTCT [American Society for Transplantation and Cellular Therapy] meetings—and immediately had stones thrown at me because in the whole Choosing Wisely Campaign, it’s not the way we do it as myeloma doctors, right? We tend to be much more liberal with our IVIG use, but that’s not really the guidelines.

Paul Richardson, MD: I do agree about that and our experience on the GRIFFIN study was very similar to what you’re describing. I think the IVIG is the important piece of the DARA addition, but, and again, clinical benefit, I think, is very clear. Other thoughts that the panel have before we move on?

Kenneth Shain, MD, PhD: I think DARA—the outcomes that it changes—is remarkable, and we should all be very happy with that. Again, the long-term use of Darzalex or DARA in these patients is the hypogamma [hypogammaglobulinemia] is a different hypogamma. I always think of patients as we’ve always had hypogammaglobulinemia with all of our therapies, but now it’s whether it’s actually numerically or just functionally. I’d say functionally these patients now are the same, but now they’re starting to get infections. We just have to really be prepared with balancing those fantastic results we see with the adding it. I think the long-term part, really, we’re going to start learning about because I think that’s where we might see even better benefit, not just in these acute settings, which means that hypogamma might be more important in our ability to protect our patients from infections, etcetera, will be really critical for us.

Ajai Chari, MD: Just to pick up on that briefly, there’s no question that there is this increased infection signal, but I think that’s the other message of ALCYONE, right? So, if the infection signal did not compromise in PFS, PFS2…

Paul Richardson, MD: That’s well said, Sagar.

Sagar Lonial, MD, FACP: I do think it’s important to think a little bit about duration of DARA if you’re going to bring it up front. When I mentioned that our algorithm is RVd/DARA [lenalidomide, bortezomib, dexamethasone, and daratumumab] for standard risk. We really give it for those first 4 cycles of therapy to deepen the response and, sort of theoretically, an in vivo purge of the product when you collect. I don’t know if that’s true or not, but I’m curious.

Paul Richardson, MD: It’s reasonable.

Sagar Lonial, MD, FACP: But we don’t continue it in the posttransplant setting beyond that.

Nina Shah, MD: It’s 2 years in GRIFFIN.

Sagar Lonial, MD, FACP: Even that’s better than some of the other trials. What I worry about with CASSIOPEIA is that we’re not going to get more information than the depth of response.

Paul Richardson, MD: Yes, because of the maintenance, exactly.

Sagar Lonial, MD, FACP: Because the maintenance is randomized to DARA versus nothing. And, if you look at the curves, they separate at the time that maintenance starts.

Paul Richardson, MD: It makes great sense. I completely agree with you, Sagar, about this DARA, the duration of DARA. What I liked when we designed GRIFFIN was that it’s every 2 months in that maintenance phase.

Nina Shah, MD: Not anymore.

Paul Richardson, MD: The point is that, even so, you go to the monthly schedule and so on. The reality then becomes, obviously, when relapse occurs you can sort of recapitulate, and we’ll come to that in a minute.

Transcript Edited for Clarity