Tisagenlecleucel as a Potential Option for Adult Patients with R/R B-ALL

Tisagenlecleucel as a Potential Option for Adult Patients with R/R B-ALL

Jae Park, MD: So, ELIANA Study was another single-arm international study, another CD19 targeted CAR T-cells, Tisagenlecleucel. The CAR design and then the way the cells were manufactured is different than Brexucabtagene. This was - ELIANA Study was studied in pediatric and young adult patients up to the age of age 25 in this single-arm study. And there was again, the pretty consistent remarkable result of a high CR and CRi combined rate of 80%, and the vast majority of the responses were MRD negative. Side effect profile [00:12:00] did appear to be a little bit better in pediatric, young adult patients, which we also have seen with other products in different age groups and where patients luckily are able to tolerate the side effects are much better, and then experience less side effects to begin with. So again, consistent results of high response rates. What was also remarkable in this setting, perhaps a little bit different than what we're seeing in adult patients with Brexucabtagene and other CAR T-cells, is the duration of remission, high event-free or relapse-free survival rates. Very few of these patients actually went to transplant after receiving CAR T-cell therapy, and about 50 to 60% of the patients in the initial report, were able to maintain the remission. So that does suggest that in a decision like Rousseau and can serve as a standalone therapy for a subset of the patients, and perhaps a larger subset than we have seen with adult patients. I think the data is certainly encouraging. Why that's the case? Whether it's particular - whether it's limited to their product, or just the age of these patients with the disease differences. I don't - we don't always have great answers to that, but it's encouraging to see the long-term remission duration after a single infusion of a T-cell and with the result that very few of these patients actually go into transplant afterwards. And that is what led to the approval of Tisagenlecleucel in pediatric, and with those patients up to the age of 25.

So, the ELIANA Study strongly support the data is used in that age group that was studied. Again the pediatric, and then for our discussion, the young adults patients we typically see in our clinic 18 to 25. Whether - and because that's what ELIANA data do suggest, and then we do have a much longer-term data than any other CAR T-cell - commercial CAR T-cell therapy that's available for the ALL patients. So I think it makes a clear choice there, but for those patients who are 26 and older, Tisagenlecleucel can be used certainly. And I think similar related compound was studied at UPenn from Dr. Frey et al, and it was published in JCO. That suggested with a split dosing regimen, they were able to get a good, very good response rates in these patients with a better safety profiles, so I think the safety is always a concern. They'll deal with patient populations, because with this product - with CD9 and CAR T-cells in general, adult patients tend to experience higher degree of a severe CRS and neurotoxicity of a quarter of the patients and compared to pediatric young adult patients. So, I think we have to balance the efficacy and safety a little bit more carefully in adult patients, but data does support - although we don't have an approval of its use, Tisagenlecleucel in adult patients. Because there are some phase - in one and two clinical - single-arm clinical trial data to support issues, but right now it's in the investigational use only in adult patients. But there are ongoing clinical trials [00:15:00] actually testing this and related compounds in adult patient population, hoping to get a better safety profiles and higher efficacy.