Ciltacabtagene Autoleucel Maintains Deep and Durable Responses in MM With Longer Follow-up: CARTITUDE-1

Thomas Martin, MD, University of California, San Francisco, discusses an updated analysis of the CARTITUDE-1 trial, in which ciltacabtagene autoleucel (cilta-cel) yielded deep and durable responses in heavily pretreated patients with relapsed/refractory MM, which were maintained at a follow-up of 28 months.

At follow-up, the overall response rate was 97.9% (95% confidence interval [CI], 92.7 to 99.7) and 82.5% (95% CI, 73.4 to 89.4) of patients achieved a stringent complete response. The 27-month progression-free survival and overall survival rates were 54.9% (95% CI, 44 to 64.6) and 70.4% (95% CI, 60.1 to 78.6), respectively. These longer-term data from CARTITUDE-1 in triple-class exposed patients with relapsed/refractory MM demonstrate deep and durable responses to cilta-cel over time, including in high-risk subgroups.

Transcript:

Hello there. I'm Dr. Thomas Martin from the University of California, San Francisco. We're going to talk today about the 2-year update of the CARTITUDE-1 study. The CARTITUDE-1 study was a phase 1b-2 study assessing ciltacabtagene autoleucel, or cilta-cel, a BCMA \-targeted CAR T-cell therapy for the treatment of patients with relapse and refractory multiple myeloma.

In this study, patients who were heavily pre-treated, had 6 prior lines of therapy, were treated with a single infusion of cilta-cel following lymphodepletion chemotherapy. After infusion of cells, patients were followed for toxicity and response. At early follow up of about 1 year, patients had deep and durable responses with overall response rates over 90% and [complete response] (CR) rates of over 60%, and the median PFS and OS were not reached.

Now, recently we did a 2-year update of this study. At 2 years, the results are essentially showing amazing responses in patients receiving cilta-cel in the relapsed/refractory setting. The key eligibility for this study is patients had to have progressive multiple myeloma. They had to have good performance status. They had to have measurable disease and they had to have received at least three prior lines of therapy, or be double refractory.

In general, patients received apheresis. The cells were sent for manufacturing. They received bridging therapy as needed, and then received cyclophosphamide and fludarabine as lymphodepletion chemotherapy. And then they received a single infusion of cilta-cel. The dose was right around 0.7 times 10 to the 6 CAR positive cells per kilogram, which translated to about 50 million cells for the cell infusion.

Now, 97 patients were treated and the median follow up that we reported was about 27.7 months. Again, these were a heavily pretreated population. About a quarter of them had high risk cytogenetics, 20% had plasmacytomas and 13% of that was extramedullary disease. 88% were triple class refractory and 99% were refractory the prior line of therapy. The results with overall response rates remain quite high at 98%. The stringent complete response (CR) rate increased to 82.5%, a very high stringent CR rate. In my mind, stringent CR is really the type of response you want to see after a CAR T-cell therapy that will translate into long term remission.

Of 61 patients who are measurable for [Minimal residual disease] (MRD), 92% were MRD negative at 10 to the minus fifth. In terms of progression-free survival (PFS), the median PFS and the overall survival (OS) were not reached. At 27.7 months of follow up, 54.9% of patients were progression-free, meaning that more than half of the patients were still in remission at the 28-month mark. Pretty amazing actually, and the results were better in those patients that achieved stringent CR and even better in the patients who were achieved MRD negativity, especially sustained MRD negativity.

Overall, the therapy was quite safe with manageable side effects. Cytokine release syndrome (CRS) occurred in about 95% of the patients. The majority of that was grade 1 to 2 and responded to measures including administration of steroids or tocilizumab or anakinra. Those drugs basically treated this quite well and in fact, the median duration of CRS was right around 4 to 5 days.

20% of patients developed neurotoxicity, most of it was [immune effector cell-associated neurotoxicity syndrome] (ICANS). Six patients developed late neurotoxicity and those patients had symptoms of Parkinsonism. They also had some cogwheeling, some tremors. Most of those were grade 1. Some of the tremors were up to grade 3. Risk factors for having that late neurotoxicity was CRS and also ICANS. And those symptoms tend to get better over time.

Our conclusion from the study was that cilta-cel had a very impressive overall response rate, 98%, again, with 83% of patients achieving a stringent complete remission, and more than half of the patients remaining progression-free at 28 months of follow up. We hope to have further follow up and further updates in the future and we're still trying to see what the median PFS and the median OS will be in this heavily pretreated population.

Source:

Martin T, Usmani SZ, Berdeja JG, et al. Ciltacabtagene Autoleucel, an Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up. J Clinl Oncol. Published online June 4, 2022. doi:10.1200/jco.22.00842