Clinical Case 3: A 56-Year-Old Man With Multiple Myeloma

Nina Shah, MD: We’ll now move on to module 3, “CAR T-cell Therapies in Multiple Myeloma,” and talk about recent advances. Before we do that, we’ll start off with another case. This is a 56-year-old man who was diagnosed with IgG kappa myeloma in January of 2016 and at the time presented with R-ISS [Revised International Staging System] and ISS [International Staging System] stage II with a free kappa of 129 mg/L and an LDH [lactate dehydrogenase] of 156 U/L. The cytogenetics were normal. There were lytic lesions detected on PET [positron emission tomography] and his past medical history is fairly unremarkable.

He received VRd [bortezomib (Velcade), lenalidomide (Revlimid), dexamethasone] induction therapy followed by high-dose chemotherapy and autologous stem cell transplant, and then went on to lenalidomide maintenance therapy. Two years later, he had a serologic progression, and upon further staging had evidence of new lytic lesions. He then received daratumumab [Darzalex]/carfilzomib [Kyprolis]/dexamethasone, but developed hypertension during follow-up, which was fairly well managed with medication. He was able to be on daratumumab/Kd [carfilzomib, dexamethasone] for 17 months, and then ultimately had progression. After that, he was started on pomalidomide [Pomalyst]/cyclophosphamide/dexamethasone. He received 3 cycles and had a PR [partial response], but very quickly progressed on treatment.

Given that he had these 3 lines, he was enrolled in the CARTITUDE-1 trial and received a single infusion of cilta-cel [ciltacabtagene autoleucel] and achieved a CR [complete response] by about 3 months following treatment initiation. He tolerated the treatment well and is doing well, so this is 1 of the success stories of CAR [chimeric antigen receptor] T-cell therapy. Let’s do a little round robin again. Josh, do you agree with this treatment approach?

Joshua Richter, MD: Of course, I’m going to say yes. At the recent ASH [American Society of Hematology Annual Meeting], your partner Thomas Martin, MD, from University of California, San Francisco presented some absolutely amazing data from CARTITUDE-1. What’s amazing to me isn’t just the depths of responses, but the durability, especially in heavily relapsed patients. We still need to work to figure out who needs a bispecific and who needs CAR T. But some type of T cell redirection needs to be part of an approach to a patient like this, and this is a great way to go. I couldn’t agree more.

Nina Shah, MD: Great. Ola, what do you think? Would you have done a similar thing?

Ola Landgren, MD, PhD: It’s an excellent idea. I agree with Josh. It’s the right thing to do in 2021 and beyond.

Nina Shah, MD: Great. Sagar?

Sagar Lonial, MD, FACP: Yes. What’s really interesting is that even though they didn’t have high-risk genetics, they clearly had high-risk myeloma, with relapse within 2 years on pretty good therapy. This is a nice result. The real question is, how long is it going to last? We don’t know the answer to that.

Nina Shah, MD: Right. Katja, what do you think about this approach?

Katja Weisel, MD: I agree. It would even be in label for ide-cel [idecabtagene vicleucel] here, because with 3 prior lines that would be a decent approach for even the second CAR T-cell construct. This is absolutely the way to go, especially in such a clinically high-risk patient. I would have done the same, with that potential and the great data we recently saw with cilta-cel [ciltacabtagene autoleucel].

Nina Shah, MD: Yes, and you make a really good point that this patient had 3 lines of therapy and there are different approval structures. In the United States, the patient would have had to have 4 lines of therapy for standard of care. Although cilta-cel [ciltacabtagene autoleucel] isn’t approved at the time of this filming, we think that it might be similar to ide-cel [idecabtagene vicleucel]. There are some things you’ve got to work out, but I agree that this is a perfect approach for this particular patient.

Transcript Edited for Clarity