Updates From ASH 2021 for Belantamab-based Combinations in Myeloma

Nina Shah, MD: Ola, I want to talk about some of the other belantamab mafodotin [Blenrep]-based combination regimens. We talked about the single agents. Sagar went over those data, and Katja mentioned it as well. But there have been some updated data, especially at the ASH [American Society of Hematology] 2021 meeting, using belantamab in combination with other drugs for relapsed/refractory multiple myeloma. There were 2 abstracts in particular that were important. One was a report from Dr Natalie Callander on the DREAMM-5 cohort using the ICOS [inducible costimulator] inhibitor and belantamab mafodotin, which is a very interesting approach, and then part 1 of the ALGONQUIN study with different dosing regimens of belantamab mafodotin in combination with pomalidomide [Pomalyst] and dexamethasone. Could you give us a brief overview of those 2 studies?

Ola Landgren, MD, PhD: The DREAMM-5 study, as you pointed out, is an inducible T-cell costimulator agonist in combination with belantamab mafodotin in relapsed/refractory patients. These were early preliminary results. It showed encouraging activity and a good safety profile, and it looks like it works even better than belantamab mafodotin, but it’s too early to definitively conclude that. We also have the part 1 results in this dose finding with belantamab mafodotin in combination with pomalidomide and dexamethasone. This was presented by Suzanne Trudel from Canada. It’s similar to what we have seen with all other drugs. If you start combining them, you improve the efficacy. Single-drug belantamab mafodotin has about a 30% overall response rate, and this combination showed 88.9%. You can boost the overall response rate and probably have longer PFS [progression-free survival]. It’s early on, but it looks better, so that’s good.

Nina Shah, MD: Yes. These combination studies are really helpful in helping us understand how to dose belantamab and what we can get away with. I enjoyed seeing this novel approach of targeting ICOS as well. Josh, it’s not just about using belantamab in the relapsed/refractory setting. We can also consider moving it up in the newly diagnosed myeloma setting. There have been several studies exploring that, and a couple of them were updated this past year at the ASH meeting. I was wondering if you could tell us a little more about the DREAMM-9 study, which is a phase 3 study looking at belantamab/RVd [lenalidomide (Revlimid), bortezomib (Velcade), dexamethasone] in transplant-ineligible patients with newly diagnosed myeloma, as well as the study of belantamab/lenalidomide/dexamethasone, or belantamab/Rd [lenalidomide, dexamethasone] in transplant-ineligible myeloma.

Joshua Richter, MD: Whenever we discuss data, we always say that you can’t compare trial to trial, and then the next thing we do is compare trial to trial. It’s a little difficult to talk about studies like DREAMM-9 and belantamab plus Rd [lenalidomide, dexamethasone] without talking about the GRIFFIN study and the MAIA study and adding daratumumab [Darzalex] in there. We’ve gone full circle. It used to be that Total Therapy was the way to go, and then everyone mocked Arkansas for doing Total Therapy, and now we’re back to where we started. This is Total Therapy but with novel agents. When we started to combine more of them as an evolution, the 4 drugs didn’t seem to be better than the 3. But now with the antibody-based therapies, we can enhance efficacy without adding significant toxicity.

Approaches like DREAMM-9 and belantamab plus Rd [lenalidomide, dexamethasone] are very interesting. But these are quite early, so both studies only had about a dozen patients. While it’s extremely encouraging, we need long-term data to follow up. The 1 interesting thing about DREAMM-9, in terms of looking at other dosing strategies, is that belantamab appears to be better tolerated when given at a longer interval, every 4 to 6 or even 8 weeks as opposed to the standard 3 weeks. In the upfront setting, where you have the other drugs doing part of the heavy lifting, I feel a little more comfortable about giving the belantamab every 2 months as long as you’re giving the RVd [lenalidomide, bortezomib, dexamethasone] with it. They’re very interesting studies and part of finding the optimal dose and dosing strategy for the drug, but we need a little more follow-up.

Nina Shah, MD: Yes. I agree. It’s interesting to bring all these things quickly to the front. It’s going faster than you’d ever be able to imagine. Ola, thinking about using belantamab in either the relapsed setting or upfront, how long do you think is the optimal duration? How do you assess response? Is there anything different about it vs other drugs that you have experience with?

Ola Landgren, MD, PhD: It’s not that different in terms of evaluating response. It would be the blood test that we do on a monthly basis when we have patients coming in for injectable infusions. If you have a longer interval with belantamab, if you combine it with RVd [lenalidomide, bortezomib, dexamethasone], as Josh mentioned, you’d still have the patient coming in for the RVd [lenalidomide, bortezomib, dexamethasone], so you’d probably check the labs in between anyway. I don’t think there’s a big difference. When it comes to the optimal duration of response, there’s no book to make the answer clear. The FDA [Food and Drug Administration] historically have probably approved drugs if the clinical benefit is about 6 months compared with whatever the control arm is. But if you pick a weak control, it can be easier to beat that. I don’t think there’s a simple answer to that question.

Nina Shah, MD: Yes. With all the choices, it’s hard to know the best thing to choose, or in which spot.

Transcript Edited for Clarity