CARTITUDE-1 Study in Relapsed/Refractory Multiple Myeloma

Nina Shah, MD: Ola, let’s talk about the abstract that was recently presented by my colleague, Dr Thomas Martin [University of California, San Francisco], which was an update of CARTITUDE-1. Can you give us a little information about the mechanism of action of cilta-cel [ciltacabtagene autoleucel] and then talk about some of the updated efficacy and safety results from this particular abstract and what this means going forward for clinical practice?

Ola Landgren, MD, PhD: First, I echo what Josh said. This is spectacular. I congratulate Tom and the whole team on the spectacular results. Cilta-cel [ciltacabtagene autoleucel] is the second-generation BCMA [B cell maturation antigen]-targeted autologous CAR [chimeric antigen receptor] T-cell. That means that the patient’s own T cells are harvested from the peripheral blood. The cells are induced by a vector that make the cells express a receptor, and this receptor has been designed to go after BCMA. It’s fascinating how quickly the field has moved. It started in mice in Bethesda, Maryland, in Steve Rosenberg and Jim Kochenderfer’s laboratory. They treated mice first, and less than 10 years later, everyone is running after BCMA in humans. It moved so fast.

You asked me for the toxicity data. Tom showed that the most common toxicity for grades 3 and 4 are the impacts on the hematologic counts. Neutropenia was seen in 95% of the patients, anemia in 68% of patients, and thrombocytopenia in 60% of patients. You also see CRS [cytokine release syndrome] happening in the majority—95%—of patients, but importantly, most of this is grade 1 and 2. There are differences between CAR T cells within myeloma when it comes to the median time to onset. With ide-cel [idecabtagene vicleucel] it can happen much sooner compared with cilta-cel [ciltacabtagene autoleucel]. The median time is around 7 days, but it ranges, like everything else. I believe Tom said 1 to 12 days. It resolved within 14 days in the vast majority—about 99%—of patients. Importantly, there’s no new CAR T cell neurotoxicity compared with previous reports.

Nina Shah, MD: These are all really important factors, and you can’t beat the response rate. That sounds like it’s something in first line. Josh, we talked about the devil in the details. Who are the right patients for this? There were some subgroup analyses that have been recently presented, especially this past ASH [American Society of Hematology Annual Meeting]. Who might be the best patient most suitable for receiving cilta-cel [ciltacabtagene autoleucel]? This isn’t going to be cheap, so we want to figure out who are going to most likely benefit. Can you review the subgroup analysis of the CARTITUDE-1 data?

Joshua Richter, MD: I view it a bit differently. I don’t view it as who’s eligible. I view it as, is there anyone who isn’t eligible for it? When you look down the subgroups of high risk, how much exposure, how many lines of therapy, how much plasmacytosis, and how much BCMA expression, they all do very well. If you’re clinically appropriate for a CAR T based on performance status and organ function, the question is something crucial that Sagar pointed out: Is the patient willing to spend a few weeks in the hospital? Does their disease have the time to wait 6 weeks for manufacturing? Everyone should get it. This is even bolstered by some of the CARTITUDE-2 data looking at earlier on where in a previous world we’re a little concerned. If we’re going to scooch it up earlier on, there’s going to be more toxicity. And as Ola pointed out, in the follow-up from CARTITUDE-1, there was no increase in ICANS [Immune effector cell-associated neurotoxicity syndrome] or neurotoxicity, similar with CARTITUDE-2. It’s not that there’s a specific subgroup that should get it. It should be strongly considered in everyone who can.

Nina Shah, MD: Yes. It’s a very interesting approach to say that most patients could qualify. And although there’s a high percentage of CRS, as Ola mentioned, this is manageable and we shouldn’t withhold therapy from a lot of these people.

Transcript Edited for Clarity