CAR T-Cell Therapy After First Relapse of Acute Lymphoblastic Leukemia

Richard M. Stone, MD: Somebody who has KMT rearranged ALL and gets a transplant in first remission, then relapses. If they’re 25 or below, are they eligible for tisagenlecleucel?

Jae Park, MD: That type of patient is eligible. If they’re first relapse they are and then they’re not primary refractory. When I mention CAR [chimeric antigen receptor] T-cell therapy, I was thinking in my mind about the clinical trial.

Richard M. Stone, MD: We’re going to talk about this first relapsed patient after transplant. Would anybody use a CAR T-cell investigational therapy in first relapse without having had a prior transplant?

Bijal Shah, MD: If there were a clinical trial that provided that option, I wouldn’t hesitate. However, there are not any to my knowledge.

Ryan D. Cassaday, MD: We have some of our own investigator-initiated CAR T-cell studies at The Fred Hutchinson Cancer Research Center that are fairly broadly written in terms of eligibility criteria. By the letter to the law, we have that option at my center, at least have in the past. Since these are still phase 1/2 trials, where we don’t have a lot of long-term follow-ups, the fact that we have two FDA [Food and Drug Administration]-approved agents with level 1 evidence, not great in terms of long-term efficacy, particularly for someone who hasn’t had a transplant yet, my usual practice would be to try either inotuzumab or blinatumomab initially and reserve the CAR T-cell therapy, be it on a study or as a standard product for subsequent lines of therapy.

Richard M. Stone, MD: If you were the FDA, you wouldn’t allow any studies to go through that allowed that type of patient to go on?

Ryan D. Cassaday, MD: At least not 1 that was on a registrational path.

Richard M. Stone, MD: Do you think that there are some certain first relapse patients after a transplant who should get it, who would be appropriate to get a CAR T-cell therapy? There were post-transplant patients on the upfront, on the original TOWER and INNOVATE trial.

Jae Park, MD: All 3 drugs have been used in all those settings. It’s more of a matter of what is the long-term goal for the patient, what is the subsequent line of therapy to help us choose between all 3 lines there. All of this, including the CAR T-cell therapy, which is under investigation over the age of 25 at this time, could be an option there. In the original study, and some of the ZUMA studies, some of the patients were allowed to not have to have BLINA and inotuzumab, although they almost always did because they had been mostly used in our trials. This is because it’s older, much before the BLINA-9 exposure or approval, that some of these patients actually received a CAR T-cell therapy ahead of that.

It’s a different era, so we have 2 approved drugs there. Theoretically, all 3 could be an option. It is difficult to study in these BLIN/INO-naїve patients because the current era that we are sitting in is at least 1 exposure. They have yet to be exposed to both. It’s hard to deny approved therapy that we know works well, especially in 80% CR [complete response], CRI [complete remission with incomplete hematologic recovery] rate with inotuzumab. We enroll in investigational therapy, especially if it’s an off-the-shelf in other CAR T therapies where we have less experience with those.

Transcript Edited for Clarity