Deepu Madduri, MD, of the Mount Sinai Medical Center in New York, NY, discusses outcomes from the phase Ib/II CARTITUDE-1 study, presented at the ASH Annual Meeting & Exposition, that assessed the CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel) in patients with relapsed/refractory multiple myeloma.

DocWire News: Can you give an overview of the study design of the phase Ib/II CARTITUDE-1 study and highlight its findings?

Dr. Madduri: CARTITUDE-1 actually consists of a phase Ib/II portion. The primary objective of the phase Ib was to characterize its safety and confirm the recommended phase II dose, as inferred by the LEGEND-2 study, but in a slightly different population. The primary objective of the phase II portion is to evaluate its efficacy. CARTITUDE-1 used JNJ4528, which now has a name, ciltacabtagene autoleucel or cilta-cel. It’s a structurally distinct second-generation chimeric antigen receptor (CAR) T-cell therapy with two BCMA-binding domains. On this study, the patients had to have progressive multiple myeloma, good performance status, had to have measurable disease, and at least exposed to three or more prior therapies, including a proteasome inhibitor, immunomodulatory drug, and an anti-CD38.

We presented data on the combined phase Ib/II portion, and what I wanted to say is that out of the 113 patients that were enrolled in and apheresed, 97 patients underwent treatment in the end with cilta-cel. What’s interesting with is that the overall efficacy rate, the overall response rate, was 97%, with 67% of these patients having stringent complete response and 93% having very-good partial response or better. We know these patients are quite heavily pretreated, as their median prior lines of therapy was six and ranged anywhere from three to 18 prior lines of therapy. To give a one-time treatment, to get these kinds of response rates, is quite exceptional. What’s actually even more impressive is that 72% of these patients are still maintaining their response at the time of data cutoff.

In addition, we know based on the MAMMOTH study, these patients with relapsed/refractory myeloma have a median overall survival of less than six months, especially if they’re penta-refractory. In this study, we know at the time of data cutoff, so a median duration of 12.4 months, we saw that the median progression-free survival (PFS) is at least a full year, and we still haven’t really reached the full median PFS yet, so it would be quite interesting to see with longer follow-up, what the PFS ends up being for these patients.

DocWire News: What are important take-aways from the study about cilta-cel?

Dr. Madduri: Some of the takeaways from cilta-cel is that it had a manageable safety profile, with 95% of the patients having grade 1 and 2 cytokine release syndrome (CRS). CRS is a very known complication of CAR T-cell therapy. And most of the patients had grade 1 and 2 CRS with very little grade 3 or higher CRS. Another complication that’s known with CAR T-cell therapy is neurotoxicity. We saw about 21% having all-grade neurotoxicity, with about 10% having grade 3 or higher.

DocWire News: How would the potential approval of a CAR T-cell agent impact the treatment of multiple myeloma?

Dr. Madduri: I think having CAR T-cell therapy for multiple myeloma is very, very needed at this moment, because like I mentioned in the MAMMOTH study, the overall survival for these patients who are penta-exposed is under six months. So here we’re giving a one-time treatment, and hopefully getting deep and durable responses. There are a lot of patients right now that are not eligible for clinical trials because they may not meet the blood counts or they have some other comorbidity that can’t get them on a clinical trial. But we’re hoping that once it’s commercially available and it’s readily available for our myeloma patients, we can actually help quite a bunch of people.

DocWire News: Where do you see the future going with cilta-cel?

Dr. Madduri: Right now, CAR-Ts are available for patients who have had at least three or more prior lines of therapy, but a lot of CAR-Ts are moving up front in earlier-line settings. So, cilta-cel is actually currently being investigated in CARTITUDE-2 and CARTITUDE-4 in the earlier-line setting and also as a possibility for outpatient administration. What we’ve actually seen happen with cilta-cel that’s a little different from the other CAR-Ts is that the median time of onset of CRS is seven days, with 89% of these patients having CRS at day four or later, and 74% of these patients having CRS at day six or later, opening up the possibility of outpatient administration, which may really help the patients down the road.