Recent Advances in the Treatment of Relapsed/Refractory Multiple Myeloma - Episode 11
Joshua Richter, MD, and Sagar Lonial, MD, FACP, review key ongoing clinical trials with belantamab mafodotin in patients with multiple myeloma and the optimal position for belantamab mafodotin in the myeloma treatment landscape.
Nina Shah, MD: Josh, I wanted to talk a little more about this combination and other upcoming applications of belantamab mafodotin [Blenrep] and maybe briefly describe the DREAMM-5 platform, which is belantamab in combination with 4 novel agents, as well as DREAMM-14 exploring alternate dosing schedules.
Joshua Richter, MD: Every time a drug is approved, despite the fact that it’s taken a decade to get it there, I feel like we all stare at it like the monolith in 2001: A Space Odyssey. It’s there and it’s wonderful, but how do we use it optimally? How do we approach dosing strategies and combinations? This is where we really start to learn about the drug. The DREAMM-5 platform is very interesting, seeking to augment belantamab with T-cell modifying agents: OX40 agonists, PD-1 [programmed cell death protein 1] antagonists, or T-cell costimulators. They’re also evaluating incorporating a gamma secretase inhibitor to upregulate BCMA [B cell maturation antigen] expression. It’s a little unclear how much it’s going to do. It seems that in the CAR [chimeric antigen receptor] T space, BCMA expression hasn’t exactly correlated with response, but I don’t know what that means in terms of ADCs [antibody-drug conjugates] or bispecifics, so it’ll be very interesting to see what those data are going to show.
Malin Hultcrantz, MD, PhD, at Memorial Sloan Kettering Cancer Center in New York, New York, is looking into a variety of different dosing strategies. As Ola mentioned, when we use carfilzomib [Kyprolis], depending on what our partner drug is, we sometimes give it once weekly or twice weekly, at 56 or 36 mg/m2. All of this needs to be ironed out with belantamab because as some of these great novel BCMA therapies are entering the fray, many of them won’t be able to be given in the community, or it will be quite complicated to give in the community. It’s very important to optimize this drug.
Nina Shah, MD: Yes. Speaking of which, Sagar, what do you think is the optimal position of this drug in the treatment continuum for patients with myeloma?
Sagar Lonial, MD, FACP: That’s a good question. BCMA as a target in general is likely going to move earlier, so if CD38 becomes standard in the induction and perhaps consolidation and maintenance phase, then that opens up an opportunity for BCMA to be used in the second and third line. The question is, how do we come up with the right dose schedule and partner if belantamab mafodotin is going to fit in that space or compete with other drugs that might also bind BCMA, whether they’re CARs or something else? These trials that were described by all of our colleagues here are perfect ways to address some of those unmet needs and think about how we transition it from the fifth, sixth, and seventh lines—which is what it was used in the trials—to second, third, and perhaps other lines based on mechanism.
Nina Shah, MD: Yes. That’s a running theme with a lot of our active multiple myeloma drugs.
Transcript Edited for Clarity