Early Trial Suggests that Targeting CLL1-Postive Cells is Effective in Treating Pediatric AML – www.oncnursingnews.com/

Findings presented at the 2021Annual Society of Clinical Oncology Annual Meeting revealed that targeting CLL 1-Positive Cells showed promise in treating pediatric patients with relapsed/refractory (R/R) AML.

In an interim analysis from the phase 1/2 trial (ChiCTR1900027684), 10 of 11 patients completely responded to anti-CLL1based CAR-T cell therapy, with CLL1-positive AML blasts eliminated within 1 month. Six patients achieved complete remission with minimal residual disease (MRD) negativity, added lead investigator Hui Zhang, MD, PhD, an assistant professor at Shanghai Childrens Medical Center and director of Guangzhou Women and Childrens Medical Center at Chinas Guangzhou Medical University.

From all the research shown, we can say that anti-CLL1 based CAR T-cells is a safe therapeutic candidate with manageable CAR T-cellassociated toxicity for children with R/R AML, he said. It is highly effective in targeting CLL1-positive AML cells with superior overall response rate (ORR) relative to conventional/novel targeting compounds.

In this study, 11 pediatric R/R AML patients aged 2 to 16 years were infused between October 2019 and January 2021 with a second-generation CLL1 CAR-T created in Zhangs laboratory. Investigators administered a single dose of CLL1 or CLL1-CD33 dual CAR-T cells (target dose: 0.3-1x106/kg) following lymphodepleting conditioning with a cyclophosphamide/fludarabine combination.

Zhang said all 11 patients experienced CAR T-cell expansionin vivoduring the first month. Five patients demonstrated persistence of T-cell expansion.

All patients experienced grade 1 to 3 cytokine release syndrome (CRS) but there were no lethal events, Zhang said. All patients experienced myelosuppression, which he said might be due to chemotherapy. Three patients experienced a grade 1/2 hepatic event. No patient experienced cardiac, renal, or gastrointestinal adverse events.

Investigators have suggested that CLL1 is a promising target because it not expressed on normal hematopoietic stem cells (HSCs), but is expressed on 85% to 92% of AML blasts cells and leukemia stem cells.2In a humanized mouse model, investigators demonstrated that CAR Ts specific for CLL-1 exhibit potent cytokine production and cytotoxicity against CLL-1-expressing AML cell lines without disrupting normal HSCs.

Investigators theorized that developing an anti-CLL1 CAR T therapy would help patients avoid the need for HSC transplant.

In 2020, Zhang published a case study of a 10-year-old girl who presented with an elevated peripheral blood blast percentage while undergoing maintenance treatment for a B-cell ALL relapse. Investigators developed a CAR containing a CLL1-specific single chain variable fragment.3

The patient received lymphodepleting chemotherapy for 4 days before CAR T-cell transfer to enhancein vivoexpansion of CAR T-cells. This was followed by a single dose anti-CLL1 CAR-T cells infusion. She experienced Grade 1 to CRS.

After completing CAR T-cell therapy, the patient achieved a complete response and was negative for MRD (<0.1%) on day 29. But the CLL1+ cells were not completely eliminated until 6 months after CAR T-cell therapy. The patient achieved a 10-month response using 1 dose of anti-CLL1 CAR-T monotherapy.

This article was originally published on OncLive as Targeting CLL1-Positive Cells Shows Efficacy in Early Trial in Pediatric AML

Continued here:

Early Trial Suggests that Targeting CLL1-Postive Cells is Effective in Treating Pediatric AML - http://www.oncnursingnews.com/