Key Factors Influence Therapeutic Choices in Penta-Refractory Myeloma

Carol Ann Huff, MD

Associate Professor of Oncology

Johns Hopkins University School of Medicine

Medical Director

Johns Hopkins Kimmel Cancer Center

Baltimore, MD

CASE SUMMARY

Eight years ago, a 63-year-old man received a diagnosis of multiple myeloma (IgG-κ)​. He lives in a rural community​. He now presents with penta-refractory disease progression after 4 prior lines of therapy that included autologous stem cell transplant, 2 proteasome inhibitors, 2 immunomodulatory drugs, and 1 anti-CD38 antibody. He has hypertension controlled with lisinopril​. His ECOG performance status is 1​.

DISCUSSION QUESTION

• What are the key factors that influence your decision making for next-line therapy?​

CAROL ANN HUFF, MD: What about this case would drive you to CAR [chimeric antigen receptor] T cells versus a clinical trial versus teclistamab [Tecvayli]? Some of the possibilities [include]: risk factors, prior treatment, eligibility, safety/tolerability, etc.

JAVIER MEADE, MD: I didn’t recommend CAR T cells. I think that at least the report that came in the New England Journal of Medicine recently [concerning [idecabtagene vicleucel (ide-cel; Abecma) in KarMMa-3 (NCT03651128)] was rather underwhelming,¹ of course considering the fact that those people were heavily pretreated and so on. But that’s essentially this patient. For the expense and the results published, I was very turned off for CAR T cells, so I decided a clinical trial, in my mind, is always the right answer because you’re offering something for which you believe, hopefully, if you have a good scientific background in your study…is better than whatever else is available. I understand that there is nothing in fifth-line therapy that is going to be a home run, but I was disappointed on what I saw CAR T-cell therapy. I still believe teclistamab may be an alternative; at least it is logistically easier than CAR T-cell therapy.

MEHMET KOCOGLU, MD: I voted for CAR T-cell therapy and the primary reason for that was the patient was coming from a rural area. At this point of time when we’re having this discussion, many of our community colleagues do not have teclistamab. I thought it would be a while before it is rolled on to centers and all of the REMS [Risk Evaluation and Mitigation Strategy] trainings dealing with this. It is likely that the patient is going to have a CRS [cytokine release syndrome]…at least. What I like about CAR T cells is they are ‘1-and-done’, for the most part, and not everything is created equal. I know we have some trials that have variable results, but I’m talking about primarily commercial CAR T cells at this point of time.… Everything happens before our eyes in the tertiary care center before the patient returns to their providers.

ARUN BHANDARI, MD: This patient received all different classes of therapies. It’s time to move into a different class of therapy. That’s probably going to give a better response. Although it is still it’s hard for me to justify the cost of therapy [based on the] outcomes.

CHRISTIAN GOCKE, MD: The biggest issue for me is how likely is it going to happen in a timely manner. If you’re giving us a guarantee when you say to refer for CAR T cells [that they will receive them], then yes, [I would choose them].

HUFF: I wish I could give guarantees.

IKECHUKWU AKUNYILI, MD: When we talk about the cost of CAR T-cell therapy, there’s also a cost to teclistamab and other therapies. When you think about the cost, it ends up being about the same, and CAR T-cell therapy is ‘1-and-done’, [whereas you] keep giving teclistamab. Selinexor [Xpovio] plus dexamethasone is reasonable. I voted for CAR T-cell therapy because of the fact that if you have somebody coming from a rural area, I think the main challenge for CAR T-cell therapy is the time to production and whether the patient needs something to hold them. But if they have the ability to get their treatment on the 1-off schedule, then it’s probably better for them. They go to the transplant center, stay for some time, then come back, and they don’t have to shuttle back and forth for a long time. Whereas if they are getting teclistamab, they might have go to there for a long time and it’s challenging. Now, there are some rural areas where most patients are elderly and they don’t even want to travel out of the place to begin with. Otherwise, a clinical trial is the ideal answer. Of course, we know that is always the ideal, but I think CAR T-cell therapy is reasonable. If the patient does not want to travel, I would usually do selinexor.

HUFF: The data for the CAR T-cell therapy and teclistamab…[have] much higher overall response rates [ORR] than the selinexor data, which is about a 25% response rate and definitely does have a challenging adverse event profile to get selinexor combinations into patients.^1-4 The dosing of selinexor that came from the original trial, which we were a part of, is too high and patients don’t tolerate that dosing, so you have to give it more on a weekly schedule. But the ORR is [approximately] 25% with a duration of a few months at best, generally speaking.¹ The BCMA [B-cell maturation antigen]-targeted therapies are much better.

The cost isn’t substantially different when you take it in totality of CAR T cells versus bispecifics for an ongoing period of time. Although it might sound counterintuitive to some patients for somebody from a rural area to get CAR T, I agree that if you had it available, it might be easier for the patient to come for a period of time and get it. There is the challenge that patients don’t always want to travel out of their rural environment for any of these therapies. All of the points that everyone has made are excellent points as to why one therapy might be preferred over another.

_References:

_{1. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023;388(11):1002-1014. doi:10.1056/NEJMoa2213614zz}

_{2. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478}

_{3. Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314-324. doi:10.1016/S0140-6736(21)00933-8}

_{4. Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381(8):727-738. doi:10.1056/NEJMoa1903455}