iwMyeloma 2025 | Important considerations for community oncologists regarding the use of T-cell therapies in myeloma

Damian Green:
All right, well, I’m Damian Green. We’re here at the iwMyeloma 2025 meeting, and I am the director of the Division of Transplantation and Cellular Therapy at the University of Miami and Sylvester Comprehensive Cancer Center. And I’m very fortunate to be joined by one of my Florida compatriots,

Rachid Baz:
Rachid Baz from Moffitt Cancer Center across the state on the west coast of Florida. I’m the myeloma section head in the Department of Malignant Hematology.

Damian Green:
We actually have a consortium together, so we interact, and it’s really a great relationship between the two institutions, I think. And we were just in a session together where we were looking at bispecific antibody therapies in myeloma and new breakthroughs. As part of that session, we also talked more broadly about cellular immunotherapy, CAR T-cell therapy, and there’s a lot of exciting stuff going on. Maybe we could just start by discussing what excites you the most in the bispecific space?

Rachid Baz:
I think the response rate is truly phenomenal. It’s a big step forward compared to some of the other therapies we’ve had. There are obviously some challenges to overcome. To me, the more challenging will be access, but also how do we mitigate infection risk? And then ultimately, how are we going to best use those agents in a different way than what was used in the trials—for example, fixed-duration therapy, etc.?

Damian Green:
Yeah, no, I think that’s a huge issue. And it’s nice to see that people are beginning to look at ways to do this, either by spacing out the drugs or not necessarily needing to have fixed-duration therapies, in the hope that that will be sufficient. I think that’s super exciting because it has been one of the—I won’t say discriminating—but one of the factors when we think about the CAR-T cell space, which I’m also heavily involved in and very excited about. The “one and done” notion of CAR-T cells certainly has broad appeal in that we treat the patients, and yes, they may have to be inpatient, although we are now developing outpatient administration, and I think that’s an exciting advance. But that said, one of the distinctions has been this issue about staying on therapy interminably with the bispecifics. Do you think we’re going to move away from that?

Rachid Baz:
I think so. I’d love to see how we do that. I mean, I think the data is limited. Obviously, when you talk to patients who’ve had CAR-T, one of the things they value the most is that they’re not on any therapy. They feel the best they’ve felt in a long time. And the immune reconstitution happens—you know, after about three months, the risk of infection kind of goes down to a really low level, to what you would see in a myeloma patient on non-immunosuppressive therapy.

You know, I think it would be nice to get to a point where we have patients off therapy. The big challenge is going to be who is the best candidate for that, what type of risk, genomic complexity, depth of response, is going to be required to be able to do that.

Damian Green
Yeah. And I can tell you, I mean, you know, we had early CAR-T cell studies, and one of the things that amazed me the most were patients who really had been told they were out of options at all, including patients who were told that hospice was their only option. And then they came to us on our BCMA CAR-T cell studies. And this is not hyperbole, although it sounds like it would be—some of those patients, one who I remember, was surfing three months – not on our advice, was surfing three months after receiving CAR-T cells, and another was whitewater rafting within less than six months of therapy. And so, truly, the dramatic changes. The problem is the patients are relapsing, but during that window—which, depending on the drug, could be three years or longer—that’s a huge advantage, these folks to be off therapy, especially if they’ve been on Revlimid and Dex and all these things that cumulatively impact their quality of life. Sounds like, though, with the bispecifics, hopefully, we’re getting there.

Rachid Baz:
Yeah, I mean, in terms of—if you subtract out the infection risk—I think some of the other side effects are going to be early on. So CRS, for example, is an early toxicity—we can mitigate it. But then subsequently, it’s infection risk, but there isn’t a tremendous impact on quality of life, I think, in terms of bispecific therapy alone, such as the diarrhea you see with lenalidomide or the cardiotoxicity you see with, for example, carfilzomib. So I think when you look at overall quality of life, those quality-of-life data look really good for those patients, even though they may be on some therapy. So the big challenge is: How do we get them off, right?

Damian Green:
Yeah, because I think I was just thinking about also this notion—you know, academic centers don’t permeate the entire geographic region. And so we obviously need community partners in all these things. Like with CAR-T cells, you know, we keep patients for 30 days, and we send them back home, but we continue to partner, answer calls, and are available, and see patients back usually at 90 days. With the bispecifics, up until this point, I think you’ve, by necessity, right, you’ve had to sort of keep them in close. How do you envision this sort of partnership moving forward?

Rachid Baz:
We’ve been actually fortunate that we’ve had a good connection with the community oncologists, but we recognized early on, a long time ago, that most oncology care in the U.S. takes place at community centers. So we have to figure out a way to deliver the therapy there. So currently, we do the ramp-up at Moffitt, and then we can transition patients quickly to the community with recommendations. We follow those patients every three or so months. So we kind of have a little touch with them, but at the same time, I think there is an uptake in community centers now, even starting to do ramp-ups.

So I think the recognition of how to manage those patients now that these therapies are there for myeloma, lymphomas, and even lung cancer—I think—is going to lead to more usage in the community.

Damian Green
Yeah, I think that’s an ideal model. You know, to my mind, before I came here, I was in Seattle at the Fred Hutch, and I’ve been a transplanter my whole career. And, you know, when we think about autologous transplant in its early days, it was only done at academic centers, and the acuity was high. And as we got better and better at managing toxicities and the capacity to provide that treatment, it became easier and easier for other places to do it. And that just increases access. And I feel like we’re just in the early days of immunotherapy for myeloma, right? Whether it’s CAR-T cells or whether it’s bispecifics, I feel like as we move forward and as we learn how to better mitigate toxicities, the same thing is already happening. I think it’s going to happen faster in this space, but definitely, it’s a critical element to ensure access for patients.

Rachid Baz
Oh, absolutely. And I think more for CAR-T—it’s a little bit simpler to wrap your head around because it’s a fixed duration, like a one-time therapy. Patients could be, say, traveling from Tallahassee, come into town, stay a month, and then eventually go back to their home. The monitoring could be done in the community without, you know, a lot of difficulties, I think. But, you know, a little harder for bispecifics still—you know, there is still some kind of maybe hand-holding that is needed, but we should try to figure out a way to get there. And I think now there is going to be, you know, more interest in looking at even maintenance post-CAR-T, right? Because we certainly have a group of patients who are relapsing soon. And I think I wonder—we would still need to partner even in that setting with the community to figure out how to do it best.

Damian Green:
Yeah. And now also, right, there’s a lot of excitement with combinations with the bispecifics, right? We heard some of that data today. And there again, it almost gets to this question: So ideally, we’re curing patients. If we’re not curing patients as yet with these therapies, then do we necessarily have to keep the pressure on all the time? Or is it actually better not to keep the pressure on their disease all the time and give them more opportunity to be at home and in between cycles of therapy and watch them closely?

Rachid Baz:
Yeah, I think we will need to have more data related to this, but you bring up a great point. It is one also to look at T-cell exhaustion that could be happening with repeated dosing, and maybe a stop-and-go approach might be more beneficial in the long run. So, we don’t know that. And then the second point is infection mitigation could be actually more easily done with a stop-and-go approach. So, I think this is something that would need to be studied further, but I think it would be a very promising way to look at this. And I think there’s been a lot of advances in the treatment, and there’s obviously more of this kind of functional cure rate. We see patients now having a lot better outcomes, and this is very positive. And yet, there is still a subset of patients who have very refractory disease, very distinguished from the bulk of the other patients who are doing wonderfully.

Damian Green:
Yeah. And I think I know you’re… We’re both at academic centers, so I think I know your answer to this question. But from my perspective, clinical trials and the advantage to clinical trials—you know, for community physicians to send their patients for clinical trials at academic centers involves a lot—you know, communication and frankly, often explaining to the patient, convincing them that they should come to us for care, not seeing those patients for a while when they’re on a trial. But to my way of thinking—with the bias of an academic center, but still—I feel like when we have these studies, the ones we heard about today, prior studies, we’re basically working out the kinks in the system that ultimately allow us to move towards a goal of not having to have those. We’re learning how to manage infection. We’re learning how to manage toxicity so that these drugs can get rolled out. But it’s sort of playing the long game, right? In the short game, patients have to be sent to us for us to figure out these things. In the long game, more patients, to my mind, are actually going to stay in the community and get these more effective therapies, as we enroll more rapidly to the studies—I guess the sooner that day comes.

Rachid Baz:
Absolutely. I mean, the only reason we have all those therapies for myeloma patients now is because of the altruism that a lot of patients have committed to traveling to centers and far from where they live, enrolling on trials, and believing in the science that we do. And I think it’s paid off for some of the patients, but also for the future generation of patients to come. I think it’s an investment that, you know, the community of myeloma physicians, caregivers, doctors in the community—all have to make—so that we can make the future better than it has been.

Damian Green:
And I think also sometimes we don’t give enough credit to the unspoken partnership with those community oncologists and hematologists who are sending us the patients, right? Because they too are kind of engaged in this process that helps us to advance the field and move science forward. But it’s not always directly linear.

Rachid Baz:
I agree, and I think sometimes you’re in clinic, and it’s easy to think about what is the second-line therapy for a myeloma patient. But then, you know, if you start adding the trials that are available, then that makes that discussion potentially longer, and your day in the clinic becomes longer. So the community oncologist is having to bear some of that brunt as well. So I think engaging the patients with those discussions is very important. And I think that’s a lot of the ways that we move this forward.

Damian Green:
And are you guys—so we have now just started to treat patients with CAR-T cells in the outpatient setting. And it took a fair bit of logistical work to set that up because we had to make sure that everything was in place so that nothing fell between the cracks. And we’ve done that now effectively, we’re sort of piloting it out. Are you guys doing that in the CAR-T cell space?

Rachid Baz:
We are. Yeah, we do most of our CAR-T in the outpatient. Still, for ide-cel, we admit the patient. But for cilta-cel, we will plan outpatient management, and usually, they’ll develop CRS around day seven, come in for a couple of days, and then they’ll be discharged back to the outpatient. And we were able to use our experience with outpatient transplant to extend that to CAR-T and now to bispecific ramp-up for the group of patients who live within an hour of the center—or are able to be within an hour of the center—who have a caregiver and have relatively preserved organ function, so we can do step-up dosing on the outpatient. And we use prophylactic toci, and I mean, your data from Miami has been very helpful as well to justify some of the prophylactic toci so that patients can receive it and insurance can authorize it, right?

Damian Green:
Yeah, I think that aligns very nicely with what’s going on here. In fact, I’m thinking—if you have a one-hour perimeter and we have a one-hour perimeter, we get pretty close actually to covering a large fraction of the sort of, you know, our catchment areas without overlapping. It kind of works nicely. So yeah, I think that’s great. And definitely, you know, the experience now, right—with giving safe preventive measures, you know, for folks in the community to know—like with cilta-cel, as you said, it’s really pretty predictable for when we’re going to see some toxicity. And so it gives us much more comfort to allow patients to stay outside of the hospital. And now with the BiTEs, the fact that we’ve learned that you can give prophylactic tocilizumab, that you can take these preventive measures, opens up a huge opportunity.

Rachid Baz:
Yeah, your data shows very nicely that, you know, one out of 10 patients will develop CRS, and then those patients will be hospitalized to manage. But, you know, and our data looks very similar, to be very honest. So as a result, the majority of patients will be able to ramp up outpatient. And I think we have to also get a lot of education out there that CRS is not a very scary side effect. A lot of the time, it is just a fever, and it is not the end of the world. So I don’t think we need to be scared necessarily of CRS. I think it’s more infection prevention down the line that could be the more concerning part that we need to sort out very well.

Damian Green:
I agree, and these speak to the same—I don’t want to harp on this transplant analogy too much—but we used to see mucositis in 70% of our patients until we learned how to prevent it with ice chips and so on. So these things are evolving. It’s early days now, but we’re already evolving quickly. I just expect it’s going to keep evolving more and more such that the community, getting patients out faster or allowing them to stay home, just becomes more realistic because we understand how to manage things. And to your point, I think Ola Landgren here and the Myeloma Group did a terrific job doing pioneering stuff, looking at tocilizumab as a strategy, which worked. And it does take a lot of work upfront to do that, right? Initially, there are questions about insurance, questions about coverage, so you have to sort of do that convincing, but once you get through that bottleneck, if you will, it pays off for sure. It pays off for patients. For the next group of patients, definitely. Any other exciting stuff that you’re working on?

Rachid Baz:
Well, I talked a little bit about ABBV-383. So, you know, 383 is an exciting BCMA bispecific. I think what I like the most about it is you can dose every three to four weeks. 60 milligrams, flat dose, every four weeks—you know, it’s very effective. And it actually makes it easier for patients who are driving a distance. You know, the one-day hospitalization cycle, day one, is not, I think, prohibitive. And when you look at, you know, the CRS rate and the neutropenia—which I think a lot of it is a class effect—but, you know, if you compare across, this agent probably has one of the lower incidences of neutropenia and possibly CRS. So I think it’s an exciting compound—it’s still in trials—and hopefully, it’ll come to the clinic soon.

Damian Green:
But that’s tremendously exciting. Those are the kinds of goals we’re actually looking for. I just saw a patient last week who lives further afield, and I think was not eligible to come in for the frequency with which they would need to get current approved BiTEs, but also probably can’t wait for CAR-T cell products. I had to find something to bridge them. And I think if we had something you can give every four weeks, that would be ideal for a patient like that.

Rachid Baz:
Yeah, absolutely. And the same—we still have to answer other questions. For example, you showed amazing data with gamma-secretase inhibitors in the context of CAR-T. The same could be said about GSI use with bispecifics. When is the best time to use it? Maybe a little bit, one or two cycles down the road, I would suspect, right?

Damian Green:
And look, you’re touching on a favorite topic of mine, but we definitely believe in some of the data that I showed—that there are things that can be done to further improve the efficacy of these antigen-targeting strategies, one of which is gamma-secretase inhibitors designed to increase the density by preventing cleavage of that surface antigen. And in fact, when we published the data, one of the things we said is, this is just what we hope is a first demonstration of something that could be done with other antigen-targeting approaches. We need to figure out ways to increase the surface density and do it safely. But maybe even with the bispecifics, soluble BCMA. It’s pretty clear—and these are —that that inhibits the efficacy of a bispecific. And it makes sense—it’s floating around and gums up the works. And if you can prevent that from happening, hopefully, you can effectuate the bispecific more easily and see a deeper effect because it’s not being blocked in any way.

Rachid Baz:
But you would think the timing with the bispecific—I would challenge you—is it early or late?

Damian Green:
Yeah. Well, I think, look, I think taking a strategy that looks at individual patients and makes a determination based on their individual parameters—for example, burden, soluble BCMA—disease burden.. And even, you know, we know not all patients respond to a bispecific. So if they’re having an inadequate response, maybe that’s a good time to say, “Huh, I wonder if either soluble… or if there’s not high enough density—let’s add in a gamma-secretase inhibitor, for example, and see if we can stimulate a better, deeper response.”

Rachid Baz:
I mean, that’s an excellent idea. I think definitely looking at burden, soluble BCMA, but also, as you said, maybe suboptimal responders, you know? We can identify in one way or another, right?

Damian Green:
I think personalizing medicine up to a point, right? There’s a point beyond which I feel like personalized medicine gets too personalized, and it’s impossible to generate something on scale that would benefit patients for anyone to be interested in doing it. It’s just a reality. But if you can personalize it to a degree within a spectrum that is reasonable, I think that’s where we need to go.

Rachid Baz:
Oh, no, for sure. That’s probably actually one of the main reasons that attracted me to come to Moffitt because there was an interest from Bill Dalton to look at personalized medicine for myeloma. And I think that we should definitely figure out a way to personalize our therapies more than the trials allow us to. The trial can give us a framework of what works, but then we have to figure out in academic centers how do we personalize that approach?

Damian Green:
Yeah, and that completely aligns with why I’m at Sylvester, which is the notion that we can be truly translational. Our center, your center, I think, are great examples of places that are conducting research, bringing it to patients, and using that to kind of move the science forward for everyone’s benefit. So it’s great to have partners in the state of Florida, frankly, where we can collaborate together.

Rachid Baz:
It’s been a pleasure also working with you, and hopefully, the partnership keeps growing.

Damian Green:
I think it definitely will.

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