Adult Relapsed Refractory B-cell Acute Lymphoblastic Leukemia: 2021 Updates - Episode 10

B-Cell ALL: Integrating Novel Therapies Into Real-World Practice


Expectations regarding where novel therapies such as CAR T-cell therapies will fit into B-cell acute lymphoblastic leukemia treatment algorithms as data from clinical trials continue to evolve.

Elias J. Jabbour, MD: This has been a great conversation, and I don’t want it to end. But before we conclude, my last question to you goes back to MRD [minimal residual disease]. Do you feel strongly about doing CAR [chimeric antigen receptor] T-cell therapy in patients who are MRD negative? We discussed B-cell aplasia and expansion of the T cells. But for the future, I’d like CAR T to be for MRD positivity, not for multiple relapses. And I’d like CAR T to maybe be a consolidation approach for high-risk patients among the MRD positivity instead of allogeneic transplant. Where do you think we’ll be in a couple of years when it comes to CAR T?

Jae Park, MD: We’re definitely going to be moving. I agree 100% with you. Just like the other therapies, by the time we get to the salvage 3 and 4 settings, they lose their efficacy. Even though these therapies are powerful therapies, as effective they are, they won’t work better than in the first- and second-line settings. The real-world data with tisagenlecleucel is quite interesting. Post-approval, there’s a substantial portion of the patients receiving CAR T with an MRD negative CR [complete response], as much as 30%. The data are quite striking in that those patients do very well. We don’t have a lot of cellular kinetics data, but they are maintaining their response and not relapsing. And those are one of the best groups. That tells me that even in those settings, hopefully we can translate that, and more of these patients may receive them post-approval.

There’s always a question of how many B cells you need for these CAR T cells to expand. If we’re using CAR T as a way to consolidate in a lot of different settings, then this will be the future, certainly for the MRD positive. Even before we get a consolidation, the first thing is that we want to use them in MRD positivity settings before the morphologic relapse. These immunotherapies tend to work better in general, and we have a lot of data to suggest that when you receive them with a low disease burden, your durability of remission is much better and your survival is better. That’s the optimal time. The trick is finding the window to administer CAR T when your disease is low burden, and to keep the burden low for this autologous CAR T-cell therapy. But the future is bright, and we can do this. Hopefully we can avoid many unnecessary transplants for some of the patients.

Elias J. Jabbour, MD: We’re very fortunate to live in a time where we’re making a difference in the outcome of ALL [acute lymphoblastic leukemia]. For years, nothing was available, and today, we have so many options. We can tell our children and grandchildren that we did something, possibly that we cured ALL, which I think we can accomplish in our lifetime.

Transcript edited for clarity.