CARTITUDE-4 Cilta-Cel Efficacy in Myeloma | Binod Dhakal, MD | ASCO 2023

My name is Dr. Binod Dhakal. I'm from Medical College of Wisconsin in Milwaukee. I'm here to talk a brief update or summary of the study that was presented at ASCO, the CARDITURE-4 trial. CARDITURE-4 is a phase three randomized study comparing silted capyloid gene or to cell or silted cell versus standard of care treatment in patients with lenalidomide refractory multiple myeloma. Silted cell is a dual binding BCMA detected CARDI therapy and it was tested and approved based on the results of CARDITURE-1 study in which patients had three or more prior lines of therapy. At this ASCO meeting, we presented the long term follow up of CARDITURE-1 where patients were shown to have an unprecedented median PFS about three years in a heavily treated setting. In the phase three CARDITURE-4 study, we aim to test silted cell in earlier lines against two effective standard of care regimens, namely PVD or that is pomalidomide voltage omip and dexamethasone or DPD that is directomap pomalidomide and dexamethasone in patients with lenalidomide refractory multiple myeloma after one, two, three prior lines of therapy. So the study design is the eligible patients are randomized one is to one into either standard of care arm with PVD or DPD and the choice of that regimen is based on physicians and with the prior exposure and prior refractoriness and then silted cell arm undergoes a pharysis, bridging, lympho depletion and receiving a cell to cell infusion. Now the important thing to note is that the bridging therapy is the same as standard of care arm either PVD or DPD based on physician choice. The primary endpoint of the study was progression free survival which is defined as time from randomization to either progression or death whichever occurs first. And a number of secondary endpoints we aim to evaluate in the study in particular the response rates, the MRD negative D rates, the overall survival, the patient reported outcomes and the safety. In the study we included we enrolled 419 patients were randomized into cell to cell 208 patients and standard of care 211 patients. In the cell to cell arm 32 patients had disease progression or died before receiving quality and they are counted as PFS events and 20 of the 32 patients received cell to cell as subsequent line of therapy. So the number of patients who were treated in the cell to cell arm as a study treatment were 176. In the standard of care arm 208 patients received standard of care therapy, majority almost 85 percent patients received DPD as standard of care where the remaining patients received PVD. When you're looking at the two groups, the two groups were well balanced in terms of baseline characteristics including in high risk profile for example patients with the soft tissue plasma cytomers with the high risk cytogenetics with triple trans refractory status. There are 22 percent of patients overall who are refractory to deratoma. So what the study showed? The study showed that it made its primary endpoint that means the cell to cell significantly reduced the risk of disease progression or death by 74 percent when compared to standard of care. The hazard ratio in this study was 0.26 which is very impressive and perhaps the best hazard ratio that has even been reported in this patient population in randomized setting. The median PFS was not reached and it was 11.8 months in the standard of care arm. The 12-month PFS rate was 76 percent in the cell to cell arm and 49 percent in the standard of care arm. At the time the median follow-up of these patients were about 16 months. Now in addition we also showed that the PFS benefit was seen in all patients all subgroups of patients including the patients with high risk subgroups which are difficult to treat patient population. We also showed that the cellular cell lead to improved or higher response rates versus standard of care. Patients in the cellular cell arm had higher overall response rates, complete response and better and the MRD negative rates compared to standard of care. Now when you look at the patients who received cellular cell as a study treatment, 176 patients, 99 percent responded, 86 percent achieved complete response or better and 72 percent with MRD negative. In the 12-month PFS rate was 90 percent. When looking at the safety the data from Cardiote 4 are consistent with the non-profile of citizen. Specifically when you look at the patients who received Cardiote as a study treatment and looking at the Cardiote-related adverse events, we found lower incidence and severity of adverse event like CRS, ICANS, motor and moment and neurocognitive events and other adverse events like cytopenia in much lower rates and severity than what we saw or what we observed in Cardiote 1 patient populations who are kind of more than three prior lines. So in summary, what to take from this Cardiote 4 data? We showed in this study when you compare with the standard of care which are two highly effective standard of care arrangements, cellular cell leads to superior efficacy responses with manageable safety profile. The PFS benefit can be seen in all subgroups including the high-risk subgroups which are difficult to treat patient population. Cellular cell leads to deep response and durable responses compared to standard of care and if you use cellular cell in early lines that could lead to improved tolerability by the patients. So all this data suggests that cellular cell could be a new standard of care for patients who are lenalidomide refractory as early as after the first relapse.