'Armored' CAR T Cells Show Early Promise in Relapsed B-Cell ALL

 At the recent American Society of Hematology annual meeting, phase I data highlighted a next-generation, CD19-targeted, interleukin-18-secreting "armored" CAR T-cell therapy that is designed to enhance persistence and antileukemic activity in relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

In this MedPage Today video, Matthew Connor, MD, of the University of Pennsylvania in Philadelphia, discusses results from the phase I study testing the CAR T-cell therapy, including safety outcomes and early efficacy signals, and how this fourth-generation platform may inform future development across B-cell malignancies.

Following is a transcript of his remarks:

We just underwent a phase I study of patients with relapsed or refractory B-cell acute lymphoblastic leukemia of our homegrown CD19-targeted armored CAR T-cell that secretes interleukin-18.

So this is a fourth-generation CAR T-cell product that aims to improve persistence and functional ability to kill leukemia. This cohort was opened recently after the product's success in the non-Hodgkin lymphoma cohort, which was published earlier this year in the New England Journal of Medicine, Dr. Jakub Svoboda's paper. And we treated thus far five patients on study and showed excellent rates of remission with tolerable toxicity that was similar to other commercially available CAR-T products.

Our primary endpoint was safety, of course, in the phase I study. And so we're specifically looking, as with most CAR-T products, at rates of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome. All patients in the study experienced CRS, all were grade 1 and 2, so manageable and treatable with tocilizumab [Actemra] if needed. And then two of the five patients treated developed immune effector cell neurotoxicity syndrome of grade 2 or 3, which were readily reversible with steroids and anakinra [Kineret], and both patients made full neurologic recovery.

So at this point we have actually stopped enrollment at this point. We've met the enrollment that we had initially planned across the different cohorts of B-cell malignancies. And so in the process now of evaluating the ALL cohort, in addition to a CLL [chronic lymphocytic leukemia] cohort, which is also presented at this meeting, and in addition to the lymphoma cohort that was already presented, with future plans to hopefully expand to more patients in the future.

https://www.medpagetoday.com/meetingcoverage/ashvideopearlsall/119164