Andrew P. Dalovisio, MD: Right now I would make an argument [that] that’s my general standard of care. I think that’s a good segue into the third portion, which we’ll talk a little bit longer about, the relapse/refractory setting. The [number] of drugs coming out right now is at a backbreaking pace. It’s an embarrassment of riches to have all these new drugs, but it’s also very confusing to wade through all the data, much like it can be in the transplant-eligible patients for induction. But I would like to pose it to [the panel]; when you’re thinking of relapse, do you divide it into late and early relapse? What are the regimens that come to your mind when you think of relapse disease?

Ryan P. Griffin, MD In terms of relapse, I think most important [is whether] patients [are] on maintenance therapy when they relapse. If someone’s on lenalidomide and their paraprotein starts popping up, I think they are Revlimid [lenalidomide] refractory. So then I’m thinking about pomalidomide regimens, carfilzomib-based regimens, like KPd [Kyprolis (carfilzomib), Pomayst (pomalidomide), and dexamethasone], things like that. Of course, definitely using our transplanters for assistance on guidance as well. But that’s where usually my head’s going to, carfilzomib/pomalidomide regimens. If someone had been on VRd [lenalidomide, bortezomib, and dexamethasone] or something like that and hadn’t seen dara [daratumumab], of course, then, [a daratumumab]-based regimen.

Andrew P. Dalovisio, MD: Sure. I think it’s very much the dealer’s choice, especially when you get to later relapses. But one of the few principles I tend to talk to fellows about is that you want to use more than 2 drugs. We have a lot of randomized trials showing that 2 drugs are better than 3 in the relapse setting. I’ll talk about not saving treatments for later. You want to give your best therapies up front in combination because you really only get 1 or 2 chances to make a meaningful progression-free survival [PFS]. However, that’s probably changing with bispecifics and CAR T [chimeric antigen receptor T-cell therapy]. The other principle I talk about is adding in a new mechanism of action or second-generation drug, or even preferably both with subsequent lines of therapy, so like a KPd, say, if they were on dara-VRd [daratumumab, lenalidomide, bortezomib, and dexamethasone]. We know [pomalidomide] works after Revlimid [lenalidomide], [and] Kyprolis [carfilzomib] works after Velcade [bortezomib] and Ninlaro [ixazomib], but Ninlaro doesn’t work after Kyprolis and Velcade. And then [daratumumab] and isatuximab, to me, are pretty much the same; you probably shouldn’t use one over the other if you’re not including something new with it. And then again, retreating patients, if they’ve relapsed 5, 10, 15 years after their transplant, certainly, reintroducing [drugs] like Revlimid and Velcade can be very reasonable. But I tend to break people down into early relapse, so first or second, vs late relapse. And we have all the FDA [United States Food and Drug Administration]-approved drugs, the Kyprolis, Pomalyst, elotuzumab regimens. And then in later relapse, so later than third or fourth line, that’s really where we’ve seen a huge influx of drugs coming in like selinexor, even venetoclax off-label, bispecifics like teclistamab, which has been FDA approved. There are about 3, talquetamab, elranatamab, and cevostamab, they’re about to be approved. And then we have 2 FDA CAR [T-cell therapies] approved, ide-cel [idecabtagene vicleucel] or Abecma, [and] cilta-cel [ciltacabtagene autoleucel], Carvykti. We probably have some other CAR Ts with different targets that are going to be approved in the next year or 2. It’s a waterfall of new drugs. What have been your impressions reading journals or looking at things about bispecifics and CAR T? Do you have some excitement about those drugs?

Kelly Pippin, MD: As far as CAR T goes, I just feel like that’s the edge of medicine. I’m like, this is the edge of where medicine is. It just seems like we’re about to go off the end of the Earth or something. It’s amazing we’re even doing CAR [T-cell] therapy—engineering T cells to be reintroduced back into the body is quite remarkable. I actually wanted to pass that back to you. I have not seen many personal patients go through CAR T with myeloma, and I wanted to see what your experience with CAR T has been with your patients thus far.

Andrew P. Dalovisio, MD: Sure. We are in the works of getting Carvykti, or cilta-cel, because that seems to be showing a little bit longer PFS, or significantly more than the Abecma [ide-cel]. Although that’s not randomized, I think that’s generally the consensus. Right now we’ve been referring our patients out. I’ve had a small handful of patients get either BCMA [B-cell maturation antigen], FDA-approved CAR T or investigational CAR Ts looking at other targets like GPRC5D. They’ve actually done really well, and I’ll talk about that data a little bit. I think the big challenge with CAR T in myeloma is that the slots are limited due to production issues. So it’s almost impossible to get these patients onto CAR T in a timely manner because they’re usually relapsing with pretty aggressive disease. The other thing is I don’t think CAR T has really been the home run that we thought it would be with myeloma. With things like non-Hodgkin lymphoma and ALL [acute lymphoblastic leukemia], we’re seeing 40% to 50% long-term acute survival rates, with very likely cure, [but] almost all these myeloma patients are relapsing a year or 2 after they get CAR T. So I think that that’s been a little bit of an upsetting trend to see. But at the same time, you need to look at that in the context of what were the other options. We’re looking at things like selinexor, Blenrep [belantamab mafodotin], melflufen [melphalan flufenamide], which are all taken off the market, or chemotherapy. And if you look at the PFS [rates] and new studies, they were literally 3 to 4 months. So why am I even giving them this drug? I think we’ve made a lot of advancements in that space. I do think, for me, bispecifics are probably going to be the most accessible, at least until we figure out this CAR T accessibility issue. One I wanted to highlight was the teclistamab, which is a BCMA-targeting BiTE [bispecific T-cell engager]. So it binds BCMA and CD3, and then recruits your own immune system. This is actually FDA-approved now based on the MajesTEC-1 trial [NCT05100862]. We’re actually administering this at Ochsner Health [in New Orleans, Louisiana,] if you have patients that need that. It took 165 patients who were heavily pretreated with 5 prior lines, 80% triple-class exposed. And at a median follow-up of 41 months, over 63% had an overall response rate. Of that, 40% had a CR [complete response and of those 40% CR, half of those were MRD [minimal residual disease] negative. So we’re seeing about a 20% MRD negativity rate with a median PFS of about a year. The benefit of these drugs is that you can give them off the shelf. You don’t have to bridge patients; you don’t have to get them a spot. It just requires a 5-day ramp-up dose in the hospital. There’s an additional BCMA-targeted bispecific [called] elranatamab that’s made by Pfizer that will probably be approved in the next 3 months. Pretty much identical safety data and outcome data. So I’m fairly agnostic between these 2 once they become FDA-approved. But I’ve had a lot of good experience with these drugs, just because of the accessibility and the off-the-shelf nature of them. There are a couple of other targets we’re looking at too for bispecifics. One is talquetamab, which targets a different BCMA target, which is the GPRC5D. And then there’s cevostamab, which targets FcRH5. We’re also seeing overall response rates of 60%- to 70%, deep responses lasting a year-plus. These are not FDA-approved, but likely will be pretty soon. So I think [there’s] a lot of exciting stuff. I think that the talquetamab or the non–BCMA-targeting drugs are the ones that really excite me because we’re seeing a pretty high infection signal that’s probably a lot higher in the real-world setting than in the study setting with these BCMA targets. I think that the infection is the one thing that really worries me, more so than any of the cytokine release syndrome [CRS] or ICANS [immune effector cell-associated neurotoxicity syndrome] with the bispecifics. If you look at the studies, while 80% of people [on] most of these drugs are getting CRS, almost none of it is grade 3/grade 4. Almost all can be treated with steroids or monitored or tocilizumab. And it happens in the first 5 days in the hospital, where we can address that. Then after that, those patients are doing fine. I think due to the bispecifics accessibility, things are going to take off in the relapse setting.

Transcript edited for clarity.