ASCO 2021 | CARTITUDE-2 trial update and management of neurotoxicities

So, in the CARTITUDE-2 trial, cilta-cel, which is a BCMA-directed CAR T-cell product was actually used in patients with different lines of previous therapy. The data that we really presented was the CARTITUDE A cohort, which are patients with a progressive multiple myeloma after one to three prior lines of therapy, including a PI and an IMiD and being lenalidomide-refractory. And they didn’t, it was not allowed that the patients were exposed to a BCMA-targeting agent and the end points were overall response rate, duration of response. And again, the overall response rate was extremely high 100s, nearly a 100%, a very high rate of complete remissions and beyond 60%. So, again, cilta-cel was shown to be an extremely effective treatment in patients with advanced multiple myeloma.

The follow-up is, is clearly too short too, to actually get a feeling about the potential progression-free survival, but the data look, look also really promising and we’ve known from CARTITUDE-1 that the 12-month progression-free survival is about, is beyond 75% and this was less everywhere, more heavily pretreated patients. So, I think cilta-cel is a, is a very interesting product to be used in the treatment of patients with pretreated relapsed/refractory multiple myeloma.

Another issue was the neurotoxicity that occurred in, in a rather small proportion of patients in the CARTITUDE-1 trial. There were especially some patients that developed delayed neurotoxicities and may have a specific form of neurotoxicity, which was a kind of neurocognitive pro-Parkinsonian like syndrome that developed quite later after the CAR T-cell infusion.

So, there was a new strategy now should use a kind of mitigation strategy, and part of this mitigation strategy was to define patients at high risk of neurotoxicity. These were patients with high tumor load with a higher, with a higher grade two or higher CRS, a prior ICANS and also patients with high CAR T-cell expansion and persistence, and it was introduced that now these patients were allowed to receive a more effective bridging therapy. So, to reduce the tumor node at the time of CAR T-cell infusion, also, there was an aggressive treatment for CRS and ICANS and in patients at high risk, handwriting assessment was performed for early detection of neurotoxicity and an extended monitoring and reporting of neurotoxicity was improved. A specific ICA assessment tool was introduced where the patients were kind of assessed for orientation, naming how they could follow commands, again, handwriting and their attention capacities.

And with this introducing this kind of early screening and early intervention, severe neurotoxicity and this late neuro toxicity that was seen in a few patients in CARTITUDE-1 could be completely prevented in these 20 patients that triggered that the CARTITUDE A cohort, and in addition in other patients also in these different CARTITUDE-2 trials also a sever neurotoxicity and late onset toxicity would be prevented.