Anti-CLL1 CAR T Cells Produce Responses in Pediatric Acute Myeloid Leukemia

In a phase 1/2 study, 8 of 11 patients with relapsed or refractory acute myeloid leukemia (AML) achieved a complete response with chimeric antigen receptor (CAR) T cell therapy targeting C-type lectin-like molecule-1 (CLL1) .

These results were presented at the American Society of Clinical Oncology (ASCO) annual meeting in 2021 by Hui Zhang, MD, PhD, of the Guangzhou Women and Children’s Medical Center in China.

dr. Zhang noted that the outcomes of AML in children lag behind the outcomes of acute lymphoblastic leukemia (ALL). Although CAR T cells have an attractive efficacy and safety profile in ALL, CAR T cell therapy in AML has been challenging due to the lack of an ideal CAR-T target.

read more

With this in mind, Dr. Zhang and colleagues developed a CAR T cell therapy targeting CLL1, which is highly expressed on AML blasts and leukemia stem cells, but not on normal hematopoietic stem cells.

From October 2019 to January 2021, 11 pediatric AML patients from two centers received second-generation anti-CLL1 CAR T-cell therapy. Three patients received CAR T-cell therapy targeting both CLL1 and CD33.

The CAR T cells grew in all patients and all patients experienced grade 1 or 2 cytokine release syndrome and severe myeloablation.

Grade 3/4 haematological adverse reactions were observed before and after infusion, but no dose-limiting toxicities occurred. All 3 patients receiving the anti-CLL1/CD33 CAR T cells experienced liver toxicity.

Eight of 11 patients had a complete response within 1 month of infusion, including all 3 patients who received the anti-CLL1/CD33 CAR T cells.

Six patients had a complete response with minimal residual disease negativity. One patient had a partial response, 1 had stable disease and 1 was unresponsive.

Six of the complete responders went on to transplant, and most were alive and responding at the time of presentation. One patient died of graft-versus-host disease.

The patient who achieved a partial response and the patient who did not respond also went on to transplant and was still alive and responding at the time of presentation.

The 2 complete responders who did not proceed to transplant were alive and responsive, but the patient with stable disease had died.

“Anti-CLL1-based CAR T-cell is a safe therapeutic candidate with manageable CAR T-cell-associated toxicity for children with relapsed or refractory AML,” said Dr. zhang. “It is highly effective at targeting CLL1-positive AML cells, with a superior overall response compared to conventional and novel targeting compounds.”

Disclosures: This research was supported by Guangzhou Bio-Gene and one of the authors of the study revealed ties to the company. See the original reference for a full list of disclosures.

Learn more about Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.

Reference

Zhang H, Bu C, Peng Z, et al. The efficacy and safety of anti-CLL1-based CAR T cells in children with relapsed or refractory acute myeloid leukemia: a multicenter interim analysis. J Clin Oncol. 2021;39:(suppl 15; abstract 10000). doi:10.1200/JCO.2021.39.15_suppl.10000

Comments are closed.