Dr Deepu Madduri: We Are One Step Closer to a Cure for Myeloma

There have been exceptional results seen in CARTITUDE-1, with a mortality rate of just over 14% and mostly grade 1 and 2 cytokine release syndrome, stated Deepu Madduri, MD, assistant professor at the Icahn School of Medicine at Mount Sinai in New York City and associate director of its cellular therapy program.

Transcript

Since your presentation of data on 29 patients at last year’s American Society of Hematology (ASH) meeting, have there been any new patient observations?

At this year's ASH, we presented the CARTITUDE-1 study, which was the combined phase 1b and phase 2 portions of the study, which had a total of 97 patients who were treated. They were heavily pretreated, as their median prior lines of therapy was 5. Despite having this heavily relapsed/refractory population—and as we know from the MAMMOTH study, patients who are penta-refractory have an overall survival of less than 6 months—we saw on the CARTITUDE study, we haven't met the median PFS [progression-free survival]. We haven't reached the median PFS yet. The overall response rate on this study was 97%, with 67% of these patients being in stringent CR [complete response] and about 93% of the patients having VGPR [very good partial response] or better. Even more exceptional is that 72% of these patients were still maintaining their response at the time of data cutoff, which was about 12.4 months.

Why is minimal residual disease (MRD) an important marker for cancer therapy?

MRD has become more of a landmark study that we do for most clinical trials in multiple myeloma, and trying to achieve MRD negativity in some studies is like their primary end point or secondary end point. Here in the CARTITUDE study, it was a secondary end point. Fifty-seven patients were evaluable for MRD, and 53 out of the 57 patients were MRD-negative. And that was about 93%. And this MRD was done by Adaptive [Biotechnologies], and it was 10-5.

What did investigators learn about adverse event (AE) occurrence in CARTITUDE-1 vs CAR T-cell treatment in general?

In the 97 patients that were treated on this study, we had a total of 14 deaths during the study, which 5 of them were due to progressive disease; 3 were due to adverse events unrelated to treatment, such as pneumonia and acute leukemia; and 6 patients had AEs related to the treatment.

With CAR [chimeric antigen receptor] T-cell therapy, one of the known side effects is cytokine release syndrome [CRS], which is the body's reaction after the CAR T cells are infused, and this is a very known complication. And another complication is CAR T-related neurotoxicity. So, looking at the study, we actually saw mostly grade 1 and 2 CRS. And what was interesting is our median time of onset with CRS was about 7 days. And regarding the CAR T neurotoxicity, any-grade neurotoxicity was about 21%, with 10% having grade 3 or higher.

In terms of managing these toxicities, we have a lot of supportive measures we can use, particularly atezolizumab, steroids, and anakinra. And I think as investigators get more and more comfortable in managing CAR T-related symptoms and side effects, we tend to give tocilizumab much earlier now, not necessarily waiting until grade 2 CRS. So I feel like these patients are managed very easily with the supportive care that we have, and particularly, they're not that high-grade CRS that we're managing to begin with.

Have you seen differences in response based on the type or the number of treatments patients have previously received?

In the 97 patients that we treated, we had a median of 6 prior lines of therapy, and it ranged anywhere from 3 to 18 prior lines of therapy. Unfortunately, we didn't see any correlation between the number of lines of therapy that they had, whether less lines of therapy meant that they had more response. I think it's just nice to actually have something to offer to these patients who are heavily refractory who have a median overall survival of less than 6 months. So I think a 1-time treatment to give these deep durable responses is what we need in our myeloma patients. It's one step closer to getting a cure.