Oncologists Discuss Obstacles to Referring for CAR T-Cell Therapy in Multiple Myeloma

EVENT REGION Maryland, Pennsylvania, Virginia

PARTICIPANT LIST Jackson Gao, MD | Raj Manchandani, MD | Attique Samdani, MD | Bo Zhao, MD, PhD | George Kannarkat, MD | Boris Darovsky, MD | Arun Bhandari, MD

John L. Wagner, MD

MODERATOR

Professor of Medicine

University of Virginia School of Medicine

Hematology and Oncology Specialist

Emily Couric Clinical Cancer Center

Charlottesville, VA

DISCUSSION QUESTIONS

• What factors should community oncologists consider when deciding whether to refer a patient with multiple myeloma for CAR T-cell therapy or opt for treatment with a bispecific at an academic center?
• Are there certain patients you would not refer for CAR T-cell therapy?

WAGNER: In terms of whether you want to opt for treatment with a bispecific or CAR T, how do you decide between those? Do you have a preference, or do you just leave it up to the academic center?

GAO: I personally send to the academic center and have them decide.

WAGNER: What is your comfort level with continuing the bispecifics in your practice after the initial treatment at an academic center? Is that something you’re embracing now?

MANCHANDANI: We’re not doing it at this point, but it’s a learning curve, like when checkpoint inhibitors initially came in. Especially with the first cytokine release syndrome and the central nervous system adverse events, we prefer the academic center starts it, and once the patient is on maintenance dosing, when they are at low risk of developing those symptoms, maybe we’ll be looking to introduce more in the community setting.

WAGNER: That’s something to think about moving forward, how comfortable that might be.

SAMDANI: Our practice here in Richmond, Virginia, is looking into the bispecifics. We are meeting with people and trying to see if we can do that. We are seriously looking into it…but it’s a team effort. There are so many people involved, so we are trying to get everyone on board: a neurologist, infectious diseases, critical care, and [other specialties].

WAGNER: Are there certain patients you would not refer to CAR T-cell therapy?

ZHAO: Some patients [have frailty], some are reluctant to go, and [some] have limited support. We have to deal with it. But my understanding is the bispecific, at this moment, is only indicated beyond the third line. We have to get them another treatment before going to bispecifics. In my area, the patient either goes to Richmond or starts the program in Virginia Beach, then comes back to the office for a bispecific antibody.

WAGNER: You’re right. Right now, in terms of the bispecifics, you’re slightly more limited, although I suspect like everything else, that indication will be changing relatively soon. One thing we can say in terms of myeloma therapy: Things change extremely rapidly with this disease. What we’re talking about in 6 months could be completely different. In terms of the CAR T, for someone who doesn’t have any support who has an issue for the 8 weeks or so, they need to be under some extra monitoring. But once they get out of that and they get a response, they do have a bit of respite.

Location could be an issue, although that might be an issue for the B-cell maturation antigen [BCMA] bispecifics as well. Age could be an issue. Many centers will do stem cell transplants if the person is in adequate shape, until age 80. We [might not] have a lower [age cutoff] for CAR T at this point; it depends on the [fitness] of the person.

CASE UPDATE

• The patient ultimately proceeded to idecabtagene vicleucel (ide-cel; Abecma) CAR T-cell infusion.
• Patient demonstrated stringent complete response at day 30.

DISCUSSION QUESTIONS

• How does earlier use of ide-cel change your practice?
• At what point in the patient’s treatment algorithm would you consider referral?
• What strategies would you consider for prescreening patients?

KANNARKAT: Comparing this to the pre–CAR T and pre-BCMA therapy eras, thinking about all the treatment options we had, we were feeling lucky when we had daratumumab, isatuximab [Sarclisa], carfilzomib, and all these second-line therapies that we didn’t have before. Now it seems like even those are not as necessary if we’re going to get as many complete molecular responses with CAR T-cell therapy. I’m not at a transplant center, so it takes extra effort to get people to go an hour or 2 hours to do these [therapies]. I’m used to picking a second- or third-line therapy and trying to milk as much time as I can out of those. But for a chance at deeper responses, for some patients, the risk is probably worth the benefit.

WAGNER: I think that’s reasonable. Does anybody else have any other comments on that?

DAROVSKY: I think that earlier use of CAR T is pretty attractive, and I would say it sounds very reasonable. But practically speaking, my guess is that we’re still going to be having some kind of bridging therapy based on the CAR T availability and how soon we can get the patient in. I don’t think it’s happening very quickly based on my personal experience.

I always talk about CAR T-cell therapy with my patients, even understanding that they are not going to end up doing this type of treatment. But I’m trying to send almost everybody, trying to convince everybody to go and talk to the team at the University of Virginia [in Charlottesville] or Virginia Commonwealth University [in Richmond], but the waiting times are still significant. The apheresis schedules are also not optimal in these big [centers], and that’s why we’re still going to end up having some of the bridging therapy anyway.

WAGNER: I think those are good points you brought up. We talked about earlier use of CAR T-cell therapy. With CARTITUDE-6 [NCT05257083], which we’re doing now, people are now getting 4 cycles of D-VRd and are then randomly assigned to a CAR T-cell therapy or an SCT and then followed by maintenance. That’s going to [lead to] a whole other talk about moving things up. We’ll see what happens there, but some people are predicting that within 4 or 5 years, we may be doing a lot fewer transplants and more CAR T-cell therapy. That remains to be seen, but we’ve already seen what happened in the lymphoma field where the number of CAR T-cell therapies for lymphoma increased and the number of transplants for lymphoma went down. We may see some of that in the future. I agree that bridging therapy is particularly important though.

DISCUSSION QUESTIONS

• What hurdles or challenges have you faced when referring patients for CAR T-cell therapy?
• How can the CAR T process be improved between the treatment centers and community oncologists?

WAGNER: What do you think can be done to improve the referral process? Where do you find the biggest problem? Is it getting the initial visit? Is it getting follow-up? Is it patient resistance?

GAO: At our practice in York, Pennsylvania, it’s definitely patient resistance. Half of my patients…don’t want to drive over an hour into Baltimore, [Maryland].

SAMDANI: Choosing the right patients [is a challenge] because a lot of them respond very well to first-line [therapy] for a long time and to second-line [therapy] as well. Do we send all the patients in the second and third line to academic centers, or do we select the patients at high risk?

BHANDARI: The biggest problem I see is that these are such expensive drugs, there are adverse events, and it is still not a cure.

SAMDANI: We all have patients whom we have been treating for a long time without CAR T, and they’re doing fine for 5 to 10 years. I don’t think we lose patients from myeloma these days, even without transplants or CAR T.

GAO: For the patients who do choose to go to Baltimore, what’s nice about the academic center is that they oftentimes have these day hospitals where they can house the patient and maybe one of their supporting family members for that period when they’re at risk for developing neurotoxicity, because it’s almost impossible for the patient to go from an hour and a half away to the academic center.

KANNARKAT: Their time away from home is a challenge and [so is] having to have a family member with them when they’re out of town. I think not everybody has the family member that can be dedicated to sticking with them 24/7 throughout their course without having to work or support the rest of the family in some way. Those are all the obstacles. I don’t know that it’s different compared with autologous SCT and allogeneic SCT. How long patients are away from home may not be as long with CAR T therapy, but it still requires an additional person to be with them.

WAGNER: Where I am, it’s typically that they’re required to have a caregiver for 30 days afterward. If they live more than 45 minutes away, they have to be closer to the center [for that period]. That’s our requirement for CAR T and for autologous SCT. For allogeneic SCT, it’s closer to 3 months. Each program will have a somewhat different requirement.

A lot of places provide free housing if the patient [has low income] or relatively [low income]. The problem is for people who need a caregiver and those who do not [have low income] but do not [have high income]. You not only have to have a caregiver who may be working but then you may have to pay for housing. It may be partially subsidized, but you have to pay a certain amount of money, so those are all potential barriers.

ZHAO: It seems like CAR T-cell therapy is a preferred treatment over bispecific antibody if the patients are candidates. Is that your impression?

WAGNER: That seems to be where things are going. One thing is cost, and CAR T isn’t necessarily curative, at least not like the non-Hodgkin lymphoma CAR T-cell therapies are. None of the people in these trials are cured. One of the questions is, if somebody is on maintenance therapy for the bispecific T-cell engagers for a couple of years, what is the cost of that? That’s an alternative, but it may not end up being that much cheaper. From that perspective, that probably bears a little more discussion.

There seems to be a movement in the field to moving CAR T earlier. But I agree, if we don’t start getting some fantastic responses, even more robust than what we saw with the ciltacabtagene autoleucel [Carvykti] data, there are issues about supply, manufacturing capacity, and cost to the system. I think those are all good questions. For example, an autologous SCT might cost $100,000, maybe $150,000, and CAR T is about $450,000. If we’re talking about CAR T up front instead of transplant, the CARTITUDE-6 trial uses lenalidomide as maintenance too. We haven’t been using a lot of maintenance therapy after CAR T, with the idea being that if you were going to give the wrong maintenance therapy, you might destroy the CAR T cells in the process and therefore decrease the efficacy. But with CARTITUDE-6, they’re using the maintenance therapy as early as 21 days after the CAR T with lenalidomide. Those are all big questions that need to be answered.

In terms of general thoughts about efficacy, the preference, at least in the academic centers, is more toward the CAR T. But if someone has disease that’s rapidly progressing and it’s not being controlled by anything, my colleagues would go right to the BCMA antibody. They will not try to go through [multiple] lines of bridging therapy to try to get them to CAR T.

_{DISCLOSURES: The participants had no known relevant disclosures.}