Discussion: CAR T-cell Therapy Access and Earlier Referral

Beth Faiman: Good morning, and welcome to this Oncology Learning Network Live updates from ASCO. And so, my name is Beth Faiman. I am from the Cleveland Clinic, Taussig Cancer Institute in Cleveland, Ohio. And I'm joined today by my good friend and colleague, Donna Catamero. 

Donna Catamero: I am from Mount Sinai Hospital in New York City. 

Beth Faiman: Thank you again. My name is Beth Faiman, and I'm so excited to be here in Chicago to share with you some ASCO updates. So, I think we should talk about CAR–T. What do you think? 

Donna Catamero: Yeah. 

Beth Faiman: Okay. So, let's talk about CAR–T delivery access and earlier referral, as immune-based therapies are introduced earlier in myeloma. Efficacy is only part of the story. For CAR–T specifically, the real-world question remains whether appropriate patients can be identified, referred, cells manufactured, treated, and monitored before they lose eligibility or become too clinically unstable. The original, as you know, studies were in heavily pretreated patients, and they could not make it to that CAR–T infusion because they were too sick. And so now we're moving these a lot earlier in the treatment paradigm. What needs to change for myeloma patients to receive CAR–T earlier and more reliably? Donna? 

Donna Catamero: I think referrals, I always say refer early, and now that CAR–T is available in the second line, I always say be one step ahead. So, when it was available in later lines, you should have been thinking about it on the previous line, but now it's on the second line. So, I am looking at the type of patient. If I see that they have high-risk features, I'll consider CAR–T as my second-line option. 

Beth Faiman: And Dara refractory is another one for me, too. 

Donna Catamero: And even if a patient is responding, I might want to get them into a referral center even when they don't need it right away. Just to establish that relationship. So refer a referral, refer even if your patient doesn't need it now, but you think that's an option in the future, and 

Beth Faiman:  Is it an opportunity to collaborate and care, and maybe provide access to clinical trials as well? Correct. You have so many clinical trials at your center as I do in mine, so alright. So, are patients being referred early enough, or only after they've exhausted their options? Have you seen any change in the last few years with earlier referrals, or are they still nothing? 

Donna Catamero: I would say it's a slight uptick again for those high-risk patients. But again, I think we're seeing this still in a little bit of a later line, not the fifth line, but not as much as in the second line, where that approval is. And I think again, when we say cure in myeloma, it was coming out of the CAR–T studies. So, we know that we can achieve long-term remission with CAR–Ts, and this is the best option I can offer a patient. So, I want to refer early. And so, I think that's where I'm seeing a gap. 

Beth Faiman: Yeah, absolutely. So, which patient characteristics should trigger referral now rather than later? I think we talked about high-risk disease, lenalidomide-refractory, anti-CD38-refractory, high-risk cytogenetics, etra, medullary disease, early relapse, and rapid functional decline. You shouldn't wait until you get there. I think it's so important to establish a relationship with a large referral center at the time of diagnosis so you can coordinate and collaborate on care throughout their journey. Right, right. 

Donna Catamero: I think a newly diagnosed patient should always have that referral, whether or not they get treated elsewhere. But you should establish a relationship because we know this is a chronic disease, and there's going to be periods of relapse. So, you need to have that relationship established early so that when the patient does relapse, you refer them right in for cellular CAR–T therapies. 

Beth Faiman: And the complexity of care is such that the larger centers where we work might have more resources to support the patient as well. And so, really collaborating, I think, is super important. So, what are some of the biggest bottlenecks today? Referral timing, manufacturing, slot bridging therapy, inpatient versus outpatient monitoring, toxicity management, caregiver requirements, payer approval? I don't know. In my experience, remember when we used to have waiting lists for who would get a slot for CAR–T? I think there are only 140 CAR–T centers in the United States, and most of them are on the East Coast, some over in California. In my mind, geographic location remains a major barrier to getting a CAR–T or a CAR–T referral. What are your thoughts? 

Donna Catamero: And I don't think there are bottlenecks anymore because manufacturing has improved. There are no wait times. If a patient comes to me today, I can schedule them for apheresis. It's insurance; if anything, it might be a slight delay. But there are still several states in this country without a CAR–T center. So, there are still some access issues. And you're right, it is coastal. We have centers on the West and East Coasts, but several states don't have access. So, I think that is really where the issue is: getting patients access to this therapy. 

Beth Faiman: And if you are of a lower socioeconomic status, and again, the distance from the center makes a difference as to whether or not you're going to get a CAR–T. Now we have this great Majestic Nine data. We have the successor two from the MES e kd. So, there are non-CAR–T options, but what are your thoughts on sequencing a bispecific TEumab? Those are three bispecifics. The other ones are approved later line of therapy after four prior lines, though. So, you can still access taima earlier with Dara. But what are your thoughts on sequencing? Would you give them a TAIMA and then go to CAR–T? 

Donna Catamero: So, we have the long-term data with CAR–T, and we saw that curve, that flattening of the curve in the CAR–T one trial. So, are these patients functionally cured? And that's where I have the data to functionally cure somebody with CAR–T. I don't have that data yet with Bispecifics, and with CAR–T, patients are off therapy. 

Donna Catamero: I have a patient seven years out from CAR–T in remission. So if I have the options, the patient has access, I would…
 
Beth Faiman: Go for a single cellular infusion. 

Donna Catamero: Yeah, I… would do CAR–T. But again, it's not an easy therapy. Patients need time off from work, resulting in lost wages. Not everyone can do that. 

Beth Faiman: But short-term and long-term goals need to be discussed. Yes, it might be a little bit of a burden on your time, but hopefully you'll be off of therapy and just supportive care. So what would make CAR–T more scalable? Shorter manufacturing time, outpatient models, standard CRS, and icans Pathways. What do you think would be the solution to getting more CAR–T to more people? 

Donna Catamero: Outpatient? More and more centers are doing this, but at the end of the day, most patients still spend some time in the inpatient setting. 

Beth Faiman: But just a short stay, usually.

Donna Catamero: A short stay. I think we need more certified centers for access and more trained support staff, such as nursing staff trained in CAR–T therapies. And I think we can, if we have this model where we can shorten the hospital stay, we could potentially have larger access. 

Beth Faiman: Absolutely. So, are we still selecting some patients for CAR–T based on system navigation and access rather than biological appropriateness? 

Donna Catamero: I think so. 

Beth Faiman: If you don't live by a CAR–T center, you can't do a CAR–T. 

Donna Catamero: Yeah. 

Beth Faiman: Yeah. I think we are. Hopefully, more referrals will come soon. This space is like, it's an embarrassment of riches. There are so many great options in early relapse, but I think getting that discussion with an oncologist or cellular physician sooner rather than later is important. So, my practical takeaway is that CAR–T planning should begin before the patient urgently needs it. There are manufacturing time insurance barriers, but we can do this as a hybrid outpatient approach. In my center, they get everything, the cellular infusion, lympho depletion, outpatient, and sometimes only spend a very few days in the hospital now. So that's nice. But thoughtful bridging therapy and proactive, productive toxicity planning are now part of optimal myeloma sequencing.