B-Cell Lymphomas Coverage from Every Angle

Won Seog Kim, MD, PhD: Early Results on Anbalcabtagene Autoleucel for Large B-Cell Lymphoma

Posted: Friday, July 8, 2022

Won Seog Kim, MD, PhD, of South Korea’s Samsung Medical Center, discusses results from a phase I/II trial of anbalcabtagene autoleucel, a novel anti-CD19 CAR T-cell therapy with dual silencing of PD-1 and TIGIT (an immune receptor present on some T cells and natural killer cells). Anbalcabtagene autoleucel was administered to patients with relapsed or refractory large B-cell lymphoma and seemed to demonstrate activity and tolerability in this dose-escalation study.


Disclaimer: This video transcript has not been proofread or edited and may contain errors.

As you know, in recent years, we are at looking more and more impressive efficacy data with the anti-CD19 CAR-T cells, but there are still a lot of failures after infusion. The most common reason of failure is, firstly, the antigen loss from the tumor cell. And the second reason is exhaustion of the manufacturer of the CAR-T cell through the high expression of human checkpoint proteins including PD-1 or TIGIT, etc. In our anbalcabtagene cells, we put it in two small healthy RNA to interfere with the expression of the checkpoint inhibitor proteins like PD-1 and TIGIT proteins. Therefore we are expecting to reduce and avoid CAR-T cell exhaustion with the cells. So in this trial, we designed those escalation part of Phase I and we are planning to have dose expansion Phase II part. So during our ASCO meeting, I presented a part of Phase I. In this Part 1 part we recruited a patient with a Relapsed/Refractory B-Cell Lymphoma with any histologic subtypes including DLBCL, and some follicular lymphoma and so on. The treatment scheme was escalation from a tenth of the targeted dose and one third of the targeted dose and finally we leached number three, our targeted dose. With that, we enrolled eleven patients. And we saw that majority of the patient experienced tumor shrinkage after the infusion. And the complete response grade was 20-82%. So it is quite the impressive outcome comparing with previous commercialized approved CAR-T cells. And based on the toxicities is quite minimal. The toxical major interest should be cytokine release syndrome and ICANS. We have five cytokine release syndromes out of eleven patients. Two patients had Grade 1 and one patient Grade 2 and two more patient had Grade 3. Interestingly, we had no cytokine release syndrome in Level 1 and we have one Grade 2 tox in Level 2 and in Level 3, we had 2 cytokine release syndrome Grade 3. That means the cytokine release syndrome is really correlating with the infusion cell dose. And we had only one ICANS patient during the trial at Level 3 but all the immune toxicity like cytokine release syndrome and ICANS was quite manageable. Majority of the patients with cytokine release syndrome received tocilizumab because we recommended tocilizumab from Grade 1 cytokine release syndrome. And one patient needed the steroid use because the patient had ICANS at the same time. So right now, we are expanding and recruiting more and more patients for the Phase 2. The Phase 2 trials are ongoing. I hope we can present the interim data of the Phase 2 part again in the next meeting.

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