Emerging Novel Therapies for Relapsed/Refractory B-Cell ALL

Elias J. Jabbour, MD: In addition to the CAR [chimeric antigen receptor] T cells, we had a lot of options presented at ASH [American Society of Hematology Annual Meeting], and I’d like to highlight some of them. For example, at [The University of Texas] MD Anderson [Cancer Center], we’re conducting the blinatumomab-ponatinib study in Ph [Philadelphia chromosome]–positive front line and relapse, which we think is an evolution of the management of Ph-positive ALL [acute lymphoblastic leukemia], where transplant used to be the only way to go. This study was open for frontline patients and relapsed/refractory patients in the front line. We’re reporting a CMR [complete molecular remission] rate of 86% and a survival of 93% at 2 years. In the relapsed setting, we also have a really good response rate—85%—and good survival, better than historical. That’s something to add to our armamentarium.

Inotuzumab was explored as well in a different abstract. We know that CAR T cells and blinatumomab don’t work as well when you have somebody with high tumor burden. There was a presentation at ASH on the role of inotuzumab in patients with extramedullary disease, and inotuzumab seems to be working well in both high and low tumor burden. Therefore, in our practice, we use it as a cytoreduction first and prepare for blinatumomab thereafter or CAR T cells subsequently. We have good data today to show the role of inotuzumab in extramedullary disease. The problem with inotuzumab is veno-occlusive disease [VOD]. We know that it’s dose dependent, especially with patients who are getting a transplant, are older, or are getting double alkylators. This has been shown in the INO-VATE trial.

At ASH, there was a postmarketing phase 4 randomized trial to show if lower-dose inotuzumab is as effective as a full dose. In this study, the first run-in phase was 1.2 mg/m2 of inotuzumab. It’s acceptable. It passed the threshold, and therefore they want to proceed with a randomized trial comparing lower-dose inotuzumab with a full dose of inotuzumab, 1.8 mg/m2. At MD Anderson, we use the lower dose of inotuzumab, and we’re doing great. We use 0.9 mg/m2 for cycle 1 and 0.6 mg/m2 for cycle 2, and we see a reduction of the VOD rate, which is good.

Are there other CD22 antibodies? Were there antibody-drug conjugates? The answer is yes. They’re being explored. The ADCT-602 is unfortunately still in a dose-escalation fashion. At the lower dose, they didn’t see much activity, but we hope that at the lower dose, we’ll see better efficacy. In the relapsed/refractory ALL setting, we have several options. We have blinatumomab. Subcutaneous blinatumomab has also shown efficacy. It’s a small cohort. Nine patients were treated, but 5 of 9 are responding to the drug being given subcutaneously 3 times a week, which is quite encouraging. There’s inotuzumab, the CAR T cells in the first generation, and we’re moving into the novel generation of CAR T cells.

That concludes the first part of the discussion I’d like to have with my colleague, Dr Park. I’ll move on to the second part of the program, which is on measurable residual disease.

Transcript edited for clarity.