ASH 2022 | The impact of sustained undetectable MRD on survival in patients with myeloma treated with ide-cel

We are presenting at ASH data on MRD assessment in the KarMMa Phase II study. I think that these are important results because whereas in all other treatment and disease settings the role of MRD, I think that by now is well established in patients treated with CAR T-cells there were some uncertainty. Uncertainty because of different response kinetics between the M-protein and MRD. Also because of somehow discordant results between very high rates of MRD negativity and the median PFS being achieved by the overall patient population enrolled in these CAR-T clinical trials.

We show in this study that MRD is of value, depth of response is of value in patients treated with CAR T-cells, but there are some nuances. For example, at the very beginning month one, only MRD status is informative, whereas CR is not informative. By contrast, since that moment till month 12, both CR and MRD negativity are critical to identify patients that may enjoy long-term progression-free survival after infusion with ide-cel.

Importantly, we also show that at the beginning, well, I would say throughout the first year after infusion with CAR T-cells, there is a high risk of having hemodiluted samples and this may induce false negative MRD results. We have also shown that detecting MRD at the 10 to the minus six level is important. These patients will relapse soon, so you need high-sensitive methods.

We show for the first time that by using flow, you can monitor MRD, yes, but you can also look to the reappearance of normal plasma cells that express BCMA. We show it that the reappearance of normal BCMA-positive plasma cells is a new marker to predict risk of progression, particularly among patients that are MRD-negative.