How early have you been able to detect a response with CAR-T in patients with relapsed DLBCL?

Responses to CAR-T cell therapy is generally very rapid. As seen in the ZUMA-1 trial median time to response was 30 days. Having said that there are patients in whom continued responses can be seen as late as 5-6 months post therapy, so patient who are in a PR at 1 month, it may be reasonable to just observe them for few more months and await the maturation of response to possibly CR.

Response to effector cellular therapies are fast due to the rapid in vivo expansion of these cells since they are armed with specificity and costimulation for rapid proliferation. The average time is a month from published clinical trials. Responses however are expected to continue to mature with time and for as long as these cells survive after infusion, the average of this survival is in excess of 12 months. Their survival is derived by their target and the type and number of the engineered costimulation. Weather this response can lead to cure over years of response is to be decided.

The earliest reported time to response is approximately 30 days (although this is only because this is when most post infusional restaging is conventionally performed across trials). However, anecdotally based on personal experience with over 100 CAR T infusions across several tumor types/cellular constructs, there are patients who exhibit abrupt disease shrinkage just several days after CAR T infusion. While this effect is confounded by the presence of peri- cellular infusional lymphodepletion with cytoactive agents, it is plausible that CAR T mediated cytoxicity plays a synergistic/primary role with inducing this prompt response in select cases.

Most importantly, however, is the well demonstrated possibility of pseudoprogression and even...