Improving Treatment Strategies for Patients with RRMM


Various treatment options for patients with relapsed/refractory MM are discussed.

Jeffrey Matous, MD: How about at your institution? How is the access to commercial CAR [chimeric antigen receptor] T-cell therapy?

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: We are very fortunate that we have both products. But we are limited by our slots every single month, and therefore it puts us in an ethical dilemma. Which patient needs to go first? How long do they have? What does the insurance payer situation look like?

Jeffrey Matous, MD: How do you manage that internally?

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: It’s challenging because we have had the list now for a little over a year. Thankfully, we have other agents such as teclistamab that have helped with some of the delays. But it sometimes boils down to where they are in their disease treatment course, what’s their insurance payer, and how quickly can we get them through the therapy. Now we also have been seeing manufacturer delays and out of spec [specification]. Once you do even get the patient to CAR T-cell therapy, you also have the concern about whether they will receive an out-of-spec product or not? Then don’t even get started on the conversation about bridging therapies.

Jeffrey Matous, MD: But I think it’s important though. I know I’ve taken with patients now to say, “Look, here’s the process, but there’s no guarantee that once we collect your T cells that we know how this is going to turn out. There are a lot of things that need to happen for your therapy to be administered.” What’s your experience with commercial CAR T-cell therapy?

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Honestly, where I am, I’m in community oncology, and CAR T isn’t an option for us.

Jeffrey Matous, MD: If your doctors have identified a patient who needs CAR T-cell therapy, what’s going on?

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Within the state of Minnesota, we have 2 main academic medical centers that can allow for the delivery of CAR T-cell therapy. We have the Mayo Clinic, and we have the University of Minnesota Medical Center. Both can do outpatient administration of CAR T-cell therapy in select areas until they establish further protocols. But that has posed some challenges. What we’re ultimately doing is we’re establishing a referring physician. Our physician will refer them to their physician. They’ll most likely have to get a second opinion. Then those institutions have to evaluate if they have the capacity to do this.

Jeffrey Matous, MD: Are they prioritizing perhaps their own patients?

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Correct. That has posed challenges. I know we’ll talk about teclistamab, which brings in a different nuance to this. I’ll look forward to that.

Beth Faiman, PhD, APN-BC, CM: In my institution, I wrote an editorial that was published in April 2023 in Transplantation and Cellular Therapy based on our experiences at Cleveland Clinic in Ohio. We developed a scoring system, not intended to be prognostic. But just to say, hey, we have this list of 100 people. How are we going to decide with 2 slots of ide-cel [idecabtagene vicleucel] a month? Then eventually cilta-cel [ciltacabtagene autoleucel] came, so there were 2 slots there. Fortunately, the drug companies are now allowing this lottery system where you’ll get 2 slots, but if Kansas doesn’t use theirs, they can open up a slot because that patient is no longer a candidate. We can go into the computer and grab that.

But again, the process of CAR T goes to the selection. First of all, [there is] the referral, then it goes to the selection. Then the patient has to get insurance approval. Then you get the apheresis. Then there’s the bridging therapy because it takes 4 to 8 plus weeks. And patients are heavily pretreated. We’re doing VTd [bortezomib, thalidomide, and dexamethasone]-PACE [cisplatin, doxorubicin, cyclophosphamide, etoposide] and all these old regimens from the ’90s to get them into remission. They’re so sick, and then we have to deal with the cytopenia from that, and hopefully they’ll still be fit enough to get those CAR T cells back.

Jeffrey Matous, MD: I know at our institution when we identify candidates, we have our Excel spreadsheet that we all use.

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: So high tech.

Beth Faiman, PhD, APN-BC, CM: I know.

Jeffrey Matous, MD: We have regular meetings where we go through the patients. At our institution, if someone is eligible for a clinical trial, then that’s where they go. Because the commercial product is in such short supply, we can get them on a treatment faster on a clinical trial than we can with commercial. With commercial right now, we’re getting slots for June collections and shortly for July collections. What am I going to do between now and then? There are delays in there that you have to deal with.

Beth Faiman, PhD, APN-BC, CM: Selinexor helps with T-cell fitness.

Jeffrey Matous, MD: The other question is, what is the best way to get these patients ready for CAR T-cell therapy? We have done a lot of PACE and gone old school a lot with bridging therapy to get patients under control. It’s a big deal. We also have discussions about whether there is an ideal patient for CAR T-cell therapy. I’m not sure we know the answer to that. But we do know about factors that play into toxicities after CAR T-cell therapy. For example, with cilta-cel, we’re pretty familiar with cytokine release syndrome [CRS] toxicity from CAR T-cell therapy, which occurs in the great majority of patients.

Beth Faiman, PhD, APN-BC, CM: Tocilizumab relieves.

Jeffrey Matous, MD: Mostly grade 1 and grade 2; tocilizumab. But the ICANS [immune effector cell-associated neurotoxicity syndrome] and non-ICANS neurotoxicities, and the movement and cognitive neurotoxicities after cilta-cell I think deserve mention. The FDA agreed and put it on the label. Is there a patient who we treat with cilta-cell where we might worry more about some of these unusual neurologic toxicities? Do any of you have familiarity at all with these toxicities?

Beth Faiman, PhD, APN-BC, CM: Yes. Cilta-cell, arguably, if you look at the duration of response for ide-cel, it’s 8 to 11 months depending on the study. Cilta-cell is longer. The response rate we heard was very high, in the 90% range. If you’re going to have a drug in somebody heavily pretreated who has a poor prognosis, trying to get the cilta-cel might be the best mechanism. But if you’re older, we do the myeloma score calculator, the frailty calculator. But we also ask ourselves just how frail are they? What is their age, and do they have a lot of comorbid conditions? Which is part of that calculator. We’ll offer ide-cel. If we have 2 slots, 1 person is 58 years old, with 6 prior lines of therapy, that’s probably going to go to the cilta-cel vs the 72-year-old who is in the same boat based on the neurotoxicity, the cytokine release, and all those others. It’s a little harder on them.

Jeffrey Matous, MD: Is there anything we can do to mitigate neurotoxicity in our patients?

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: Not really, not that I’m aware of. I think there are different ways, you touched on the tocilizumab in the setting of cytokine release syndrome. I totally agree that we are much more aggressive with our tocilizumab administration in multiple myeloma than we are in LBCL [large B-cell lymphoma]. But in terms of mitigating neurotoxicity, I don’t think there is or I’m not aware.

Jeffrey Matous, MD: With cilta-cel there’s a thought that high tumor burden patients probably have more neurotoxicity. Our ability to deliver better bridging therapy or cytoreductive therapy before we treat patients is critical. I also think early intervention for CRS is important because when CAR T first came out, if it was a grade 2 CRS, that’s when we were using tocilizumab.

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: It’s at time of first fever here.

Jeffrey Matous, MD: We have an itchy trigger finger with tocilizumab at our institution.

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: We sure do, now that there’s not a shortage anymore.

Jeffrey Matous, MD: Because of trying to mitigate that risk of significant neurotoxicity. We’ve definitely seen that. Is there anything else for logistical barriers or hurdles or unusual adverse effects for CAR T-cell therapy that we haven’t discussed?

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: I think the only thing we didn’t touch on is more of the long-term toxicities, to your point Beth, about survivorship as it relates to patients using CAR T. We’re learning a lot more with the patients who have received CAR T about the hypogammaglobulinemia, going back to the discussion about immunoglobulin. The B-cell aplasia, the infections, what vaccine schedule do you use? I know we’re transposing some of our information from autologous transplant, but is that really the right vaccine course? I think survivorship and CAR T is a rich area of exploration and understanding. It is very challenging. The B-cell aplasia, do you or do you not use eltrombopag? How much of it do you use? How much growth factor do you use?

Beth Faiman, PhD, APN-BC, CM: I use it.

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: We do too, maybe a little too much. But we do also use it. There is a lot to be said about the long-term toxicities.

Jeffrey Matous, MD: Has anyone had to infuse autologous stem cells after CAR T-cell therapy?

Beth Faiman, PhD, APN-BC, CM: We have not yet, but we’ve thought about it. We have patients who hang around a hemoglobin level of about 8 g/dL that just won’t get better. But we’re not transfusing them if they’re not symptomatic anymore. If the platelets are around 20,000 or 15,000, we’ll use the platelet growth factors. But we have some patients who have had lots of treatments, 10 or 12 prior therapies, and their bone marrow is sad and it’s not working. Then if you have a plasmacytoma in the pelvis, a large field of radiation, their counts just aren’t coming back. We’ve discussed it, but we have not yet in my institution.

Jeffrey Matous, MD: We’ve done it. We’ve done it because we have cells.

Beth Faiman, PhD, APN-BC, CM: Does it work?

Jeffrey Matous, MD: Yes. I always tell people that you have your seed in the soil. It depends, if the soil is reasonably healthy and you put cells in, you’re going to get some reconstitution of blood counts.

Beth Faiman, PhD, APN-BC, CM: What do you do to prepare them for that reinfusion of stem cells? Do you do any kind of chemotherapy or growth factor?

Jeffrey Matous, MD: Nothing, we just dump them in.

Beth Faiman, PhD, APN-BC, CM: It sounds so scientific.

Jeffrey Matous, MD: …and put them in.

Beth Faiman, PhD, APN-BC, CM: What about reimbursement for that?

Jeffrey Matous, MD: That’s a really good question for our administrators.

Transcript edited for clarity.

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