Tandem Meetings 2023 | Survey on the evaluation and management of DLBCL following suboptimal response to CAR-T therapy

In 2021, the Committee on Practice Guidelines for TCT, I collaborated with them to get a survey to see, how do we treat patients who have progressed or have not responded to CAR T-cell therapy? I presented at the meeting our results. We did talk about the demographics of the respondents. It was a survey, so the respondents were all clinicians. They were transplant and cell therapy physicians that were either lymphoma-specific or they were general transplant cell therapy physicians. Anyway, we got their responses, looked at their demographics, and then went straight to discuss the results to see, does the field have a consensus or are there different opinions on certain aspects?

We found that, as far as surveillance imaging, many centers do it at different time points. A lot of centers would doing it at a three-month, a one-month, six-month, 12-month time point. But again, I think the most consistent was the three-month time point where everyone, almost 90% of respondents, wanted to see a scan at three months. So I think there’s some room to look at, how frequently do we need surveillance and when do we cut down on surveillance in the early post-transplant period?

Then we went on to look at, how do we approach failure? What do we consider failure? When would people initiate workup for what they call CAR-T failure? Is it specifically in the scenarios of partial response and stable disease? We found that if patients have partial response at the 30-day or the 1-month mark, then there wasn’t much enthusiasm to do for the workup. Most people would just want to observe them. However, there was much more enthusiasm if it was stable disease at the one-month mark or if it was partial or stable disease at a three-month mark. So that was of interest as to who would approach a failure and when.

Then the survey went on to talk about some of the things, like if we consider that the patient has failed CAR or if we are highly suspicious, then what would be the next steps and workup? Most people would, at this point, not adopt looking for MRD. Most people would want to get a biopsy. If they did get a biopsy, they’d want to know what the CD19 status is, especially if they’re given a CD19 CAR or a CD22 if they’re given a CD22 CAR. So they want to know that. I think some of that stems out of where we are all trying to figure out what is the mechanism of relapse? Is it antigen escape, which could be the loss of the antigen, or is it other mechanisms such as CAR-T persistence or other things? We did find that they wanted to know the CD19 status or the antigen status.

We also wanted to know if they were interested in knowing, is there CAR-T persistence? A lot of the respondents felt that they would like to know. Some did not know if they wanted to know we had that option, also. The thing is that there is no commercially available assay, at least there wasn’t in back in 2021, which is, people wanted to know, but we didn’t have a way of knowing. So then many clinicians would look at B cell aplasia as a surrogate marker for CAR-T persistence. There is no good data supporting that. In fact, there was again, heterogeneity in that approach. Many people felt that this was absolutely not the way to do to this had no correlation and some felt that there was correlation. So if you look at the responses was almost 50/50.

We also wanted to see if, in choosing the next line of therapy post CAR-T cytopenia, how often is that an issue? I would say a lot of people, when I say a lot, I think only 5% said that it’s rarely an issue. Everyone else had experienced this issue or anticipated experiencing this issue at least sometimes, and some of them really always. So I do think that that’s something that has to be taken into consideration and can affect choice of next therapy or enrollment into clinical trial.

Then we looked at salvage regimens. Choice of salvage regimen, depending on the CD19 status, assuming that it was a CD19 CAR that the patient got, CD19-positive relapses, we asked to see the first choice. So we gave a rank order of around 13 choices, 12 to 13 choices, and wanted the respondent to choose what will be their top choice. And then they could rank the second choice, the second one as being whatever they would choose as top. We found that the top three choices were an alternate CAR with a dual or other antigen, the second was a bispecific, and the third was a clinical trial, which would be a non-CAR-T clinical trial, like a non-cell therapy clinical trial. When we looked at the CD19-negative or CD19 unknown, we found similar three choices. It was interesting that, despite CD19-positive or CD19-negative, the top three choices stayed the same, with the most frequently chosen choice being an alternate CAR.

Some of our next questions were about, once the patient goes through the salvage and they get into a CR, what is the role of a transplant? So we asked specifically if respondents would consider an allogeneic transplant, and we had a response, almost 90%, who would consider an allotransplant, unanimous. When it came to an autologous stem cell transplant, we were, again, really at the 50/50 as to whether there is a role for an autotransplant in patients that are transplant-naive that have now achieved the CR after salvage post CAR-T. And this is CAR-T in the third-line setting.

And then lastly, one of our questions was about, what about patients that have a partial response and you watch them for many months and nothing changes? They continue to stay in a partial response, what would be the next steps? Would you want to just go ahead and transplant them or would you want to start salvage? Do you want to observe? Do you want to biopsy? We allowed the participants to actually choose any or all of these options, and we found that not much enthusiasm really for transplant or salvage. Quite a few, many, would want to biopsy or observe. MRD status was also an option and there was, again, it’s not ready in the field yet, so not yet.