Luciano J. Costa, MD, PhD, on Multiple Myeloma: Subgroup Analysis of CARTITUDE-4 on Ciltacabtagene Autoleucel

We're presenting the results of the CARTITUDE-4 focusing on the patients with one prior line of therapy, with emphasis on the patients with functional high-risk myeloma. Functional high-risk myeloma has long been recognized as those patients who have a progression within 18 months of the transplant or 18 months of the initial therapy. And that's a population that's particularly hard to treat, and is a population that has not been well represented in most randomized clinical trials. CARTITUDE-4 was a trial that compared cellular therapy, cell-to-cell and anti-BCMA autologous CAR-T cell therapy with a standard of care which was DARA-PD, or PVD in patients with one to three prior lines of therapy. And that was a very positive study that actually supported the approval in the U.S. and other jurisdictions of cell-to-cell as a therapy for patients with one to three lines of therapy as long as they were exposed to a proteasome inhibitor and exposed and refracted to lenalidomide. one of the question is I think with everybody's mind is, should we use this powerful therapy even in second line therapy with patients with one prior line? And this abstract helps to answer that. So we had in the overall study, we had 60 patients with one prior line of therapy on the cell-to-cell arm and 60 patients on the control arm. And of those 40 and 39 would meet criteria for functional high risk. And what we saw is for all patients with one prior line of therapy, cell-to-cell greatly reduced the risk of progression or death and led to a much higher rate of response, complete response and MRD negative response. And that effect was also seen. And if anything was magnified on the patient with functional high risk where cell-to-cell led to a more than 70% reduction in the risk of progression and death by leading to deeper and longer lasting responses. Of course, CAR-T cell and cell-to-cell has some unique toxicities such as cytokine release syndrome and ICANS, things that are on the back of everybody's mind as we consider those therapies. And what we saw is for this one prior line of therapy population, including the function of high risk, the rate of grade three or higher adverse events and severe adverse events was very similar between the two arms. When you look at those events of special interest CRS for example, that was very common. About 60% or more of the patients on the cell-to-cell arm developed those adverse events, but very rarely they were of high grade. There was one single case of high-grade CRS. The same thing for ICANs. There was less than 5% among the patients receiving cell-to-cell. And we had essentially one case of Parkinsonism, which is really consistent with the overall safety profile of cell-to-cell. So in general, this abstract give us some very tangible, useful data that patients with one line of therapy who have a lenalidomide refractor myeloma and proteasome inhibitor exposed myeloma do benefit from cell-to-cell over a standard of care. And that benefit is particularly important and robust among the patients with the functional high-risk disease.