Journal
JOURNAL OF HEMATOLOGY & ONCOLOGY
Volume 15, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13045-022-01308-1
Keywords
Chimeric antigen receptor; Acute myeloid leukemia; C-type lectin-like molecule 1
Categories
Funding
- General Project of National Natural Science Foundation of China [81970180]
- Key Science and Technology Support Project of Tianjin Science and Technology Bureau [20YFZCSY00800]
- Tianjin Key Medical Discipline (Specialty) Construction Project
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This study evaluates the efficacy and safety of CLL-1 CAR-T cell therapy in adults with R/R AML. All patients developed cytokine release syndrome (CRS), but none developed CAR-T cell-related encephalopathy syndrome (CRES). Despite severe pancytopenia in all patients, a 70% complete response (CR) or CR with incomplete hematologic recovery (CRi) rate was achieved.
Relapsed or refractory (R/R) acute myeloid leukemia (AML) has a poor prognosis. In this study, we evaluated chimeric antigen receptor (CAR) T cell therapy targeting CLL-1 in adults with R/R AML patients. Patients received conditioning chemotherapy with cyclophosphamide (500 mg/m(2)) and fludarabine (30 mg/m(2)) for 3 days and an infusion of a dose of 1-2 x 10(6) CAR-T cells/kg. The incidence of dose-limiting toxicity was the primary endpoint. Ten patients were treated, and all developed cytokine release syndrome (CRS); 4 cases were low-grade, while the remaining 6 were considered high-grade CRS. No patient developed CAR-T cell-related encephalopathy syndrome (CRES). Severe pancytopenia occurred in all patients. Two patients died of severe infection due to chronic agranulocytosis. The complete response (CR)/CR with incomplete hematologic recovery (CRi) rate was 70% (n = 7/10). The median follow-up time was 173 days (15-488), and 6 patients were alive at the end of the last follow-up. CAR-T cells showed peak expansion within 2 weeks. Notably, CLL-1 is also highly expressed in normal granulocytes, so bridging hematopoietic stem cell transplantation (HSCT) may be a viable strategy to rescue long-term agranulocytosis due to off-target toxicity. In conclusion, this study is the first to demonstrate the positive efficacy and tolerable safety of CLL-1 CAR-T cell therapy in adult R/R AML.
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