Saad Zafar Usmani, MD, FACP, MBA, Chief of the Plasma Cell Disorders Division, Levine Cancer Institute, Charlotte, North Carolina, shares 18 months of data from the CARTITUTE-1 study of ciltacabtagene autoleucel, a BCMA-directed CAR-T therapy, in patients with heavily pre-treated relapsed/refractory (R/R) multiple myeloma MM), the data of which are being presented at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Transcript

Hi, my name is Saad Usmani. I'm the chief of Plasma Cell Disorders Division at the Levine Cancer Institute in Charlotte, North Carolina.

Ciltacabtagene autoleucel is a BCMA-directed CAR T cell therapy. The original trial was done by BioLegend in China, which looked at the original efficacy in that patient population.

The objective of the CARTITUDE-1 study was to look at the safety and confirm that the CAR T cell dose that was seen in the population in China in a more relapsed/refractory myeloma patient population is more relevant to the US practice, and then also look at the safety profile, as well as PFS and survival analyses with subsequent follow-up.

The phase IB portion of the study looked at the dose that was being confirmed and that was 0.71 million CAR T-positive cells per kilogram body weight. The patient population in both the phase IB and II portions were folks who had had at least three or more prior lines of treatment or were double-refractory and patients had to have prior exposure to PI, IMiD, as well as anti-CD38 monoclonal antibodies.

A total of 113 patients were enrolled. A total of 97 patients eventually ended up getting the product. Primary reason for patients not making it to the product was disease progression-related events. Of the 97 patients that were dosed, the median prior lines of treatment was about 6, and almost every patient had refractoriness to their last line of treatment—96 out of the 97.

This study has previously been presented at ASH with a 12-month follow-up, and this is the 18-month follow-up that I'm presenting. What we find is an overall response rate of 98 percent. At the 18-month follow-up mark, the stringency rate is gone up to about 80 percent.

Within evaluable patients, the MRD-negativity rate was 92 percent. The 18-month PFS was 66 percent. The 18-month overall survival was 81 percent, so very impressive results. Patients did have CRS and those data haven't changed. There were no new safety signals observed because now patients are in long-term follow-up. There were 5 out of 97 patients who did have neurocognitive movement disorders.

What was discovered is that patients who had high burden of disease, or developed Grade 2 or higher CRS, or ICANS, or they had a high persistence of CAR T cells, those patients were at a higher risk of developing movement or neurocognitive issues.

Doing more aggressive cytoreduction of disease in the subsequent CARTITUDE program along with more aggressive management of CRS and ICANS, led to improvement and mitigation of that kind of side effects.

If I were to summarize, overall, what we're finding is there's no new safety issue that has been observed. The PFS and overall survival at the 18-month follow-up mark appears to be quite impressive. There are ongoing phase II and phase III studies with cilta-cel in earlier relapse setting that we're hoping we're able to report on in future congresses.

Early look data is being shared for early relapse setting in another abstract at ASCO. It's called the CARTITUDE-2 study. I believe that based on the study data, the study sponsor has submitted these data for regulatory approval, and it's under review. We do not have any direct applications of the data to the real-world clinical practice.

What I do want to note is that the CARTITUDE-2 trial and the CARTITUDE-4 trial are ongoing. At the very least, what we can find is encouraging data that support ongoing clinical investigation. In some ways, these data also inform the community at large that this is an option available in clinical trials, and their patients can potentially pursue it.

The ongoing CARTITUDE-2 study has multiple arms. That includes patients who are in their early relapse 1 to 3 prior lines, patients who have high risk disease in the frontline setting, patients who have had prior BCM exposure as well. Many different questions are being asked in those cohorts, and I think that's important.

Then in the CARTITUDE-4 study, it's a randomized phase III study of standard-of-care, triplet regimens compared to cilta-cel. That will be a very important study which may impact our clinical practice in the future. That's the direction that this study is leading toward.

I wouldn't be surprised if we're asking questions and subsequent CARTITUDE protocols even for the newly diagnosed patients.