CARTITIUDE-1: BCMA-targeted CAR T-cell therapy shows high response rates in patients with multiple myeloma
Prof Deepu Madduri - Mount Sinai, New York, USA
I actually presented at ASH 2019 the CARTITUDE-1 study which is a phase Ib/II of JNJ-4528 in relapsed refractory multiple myeloma patients. The primary objective of the phase Ib portion was to characterise safety and confirm the phase II dose as informed by the first in human LEGEND-2 study which also used the same CAR construct. The phase II portion was to evaluate efficacy.
So in the data that we presented today we only talked about the phase Ib portion of the study which enrolled 29 patients with a median age of 60 and half of them were female. All of these patients were heavily pre-treated as their median prior lines of therapy was five. 100% of these patients were triple exposed and 86% were triple refractory. We also saw. 72% of the patients were penta-exposed and 31% of the patients were penta-refractory.
The most common adverse event grade 3 or higher was haematological with non-haematological AEs of grade 3 or higher very uncommon. Two patients had increased AST and one patient had increased ALT and one patient had diarrhoea. All but two patients had what’s called cytokine release syndrome with 86% of the patients having mostly grade 1 and 2 CRS. Neurotoxicity was also very uncommon in this study with 10% of the patients having any grade of neurotoxicity.
In terms of the efficacy, as I mentioned, these patients are all very heavily pre-treated and what we found is that we saw 100% overall response rate. So every single patient on the study had a response, every single person had a reduction in their tumour paraprotein and 27 of the 29 patients are still disease free at a median of six months follow-up.
Another thing we look at for multiple myeloma clinical trials are minimal residual disease, meaning is there any cancer cells left in their bone marrow. We found that 17 patients who were evaluable were all MRD negative at the time of latest assessment.
So, in the end what we found is that the phase Ib portion confirmed the dose so that we could use that moving forward. We also saw that it was safe and had a manageable toxicity profile and patients who were heavily pre-treated disease are having early and deep durable responses with 100% overall response rate. 69% of the patients are in complete remission or better.
Right now we completed the phase II portion of the study which is going to characterise efficacy and so we need to see what the data is going to bring in the long term. We also initiated phase II and phase III studies where we can move the product up to earlier lines of therapy instead of waiting until three lines of therapy and seeing if that will give patients even more benefit.
JNJ-4528 just recently got FDA approval, breakthrough designation, for relapsed refractory myeloma.