Early Trial Suggests that Targeting CLL1-Postive Cells is Effective in Treating Pediatric AML

Findings presented at the 2021 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 of the phase 1/2 study (ChiCTR1900027684), 10 of 11 patients fully responded to anti-CLL1-based CAR-T cell therapy, eliminating CLL1-positive AML blasts within 1 month. Six patients achieved complete remission with minimal residual disease (MRD) negativity, added lead researcher Hui Zhang, MD, PhD, an assistant professor at Shanghai Children’s Medical Center and director of the Guangzhou Women and Children’s Medical Center at China’s 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 cell-associated toxicity for children with R/R AML,” he said. “It is highly effective in targeting CLL1-positive AML cells with a superior overall response (ORR) compared to conventional/novel targeting compounds.”

In this study, 11 pediatric R/R AML patients, ages 2 to 16, were administered second-generation CLL1 CAR-T in Zhang’s lab between October 2019 and January 2021. Investigators administered a single dose of CLL1 or CLL1-CD33 dual CAR-T cells (target dose: 0.3-1×106/kg) after lymph-depleted conditioning with a combination of cyclophosphamide/fludarabine.

Zhang said all 11 patients experienced CAR T cell expansion in vivo during the first month. Five patients showed persistence of T cell expansion.

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

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

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

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

The patient received lymphodepletive chemotherapy for 4 days before CAR T cell transfer to enhance the in vivo expansion of CAR T cells. This was followed by a single dose infusion of anti-CLL1 CAR-T cells. She experienced grade 1 to CRS.

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


Zhang H, Bu C, Pen Z, et al. The efficacy and safety of anti-CLL1-based CAR-T cells in children with relapsed or refractory acute myeloid leukemia: a multi-center interim analysis. J Clin Oncol. 2021;39(suppl 15)::10000. doi:10.1200/JCO.2021.39.15_suppl.10000Tashiro H, Sauer T, Shum T, et al. Treatment of acute myeloid leukemia with T cells expressing chimeric antigen receptors targeting C-type lectin-like molecule 1. Mol Ther . 2017;25(9):2202-2213. doi:10.1016/j.ymthe.2017.05.024Zhang H, Gan WT, Hao, WG, et al. Successful anti-CLL1 CAR T cell therapy in secondary acute myeloid leukemia. Front Oncol. 2020;10:685. doi:10.3389/fonc.2020.00685

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

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