Unleashing the Power of CD19 CAR-T in Relapsed AML: Findings from a Prospective Single-Center Clinical Trial

Purpose: The relapsed t(8;21)(q22;q22.1) acute myeloid leukemia (AML) patients face an unfavorable prognosis and limited therapeutic options. To address this challenge, we evaluated the efficacy and safety of CD19 chimeric antigen receptor T-cell (CAR-T) therapy in these patients. Our recent retrospective study first reported favorable responses in two patients with t(8;21) AML, indicating significant progress in this field ^[]. This prospective single-center clinical trial aimed to assess further the safety and efficacy of CD19 CAR T-cell therapy in CD19-positive relapsed t(8;21)(q22;q22.1) AML patients.

Methods: Ten relapsed CD19-positive t(8;21) AML patients were enrolled in this trial (NCT03896854). Following tumor reduction chemotherapy, all patients received a dose-escalated infusion of 5-20 ×10⁶ CD19 CAR-T cells/kg after lymphodepletion chemotherapy with cyclophosphamide (300 mg/m² for 3 days) and fludarabine (30 mg/m² for 3 days) from days -5 to -3. The dose distribution was 10%, 30%, and 60% over three days. Primary endpoints included hematologic toxicities, non-hematological toxicities, and CAR-T-related side effects, while secondary endpoints were complete remission rate, overall survival (OS) and leukemia-free survival (LFS).

Results: The cohort comprised ten patients (8 males, 2 females) aged 13 to 52 (median age 31). The median CD19 expression in AML blasts was 52.8% (22.6%-97.1%). Hematologic relapses were observed in eight patients, with molecular relapses in two. Two patients relapsed post-allogeneic transplantation. Notably, adverse mutations in the KIT and TP53 genes were identified in the other two patients with multiple relapses (Patients 2 and 3, respectively). As of April 2024, the median follow-up duration was 11.6 months (3.0-76.9 months). In our study of ten patients with relapsed t(8;21) AML, CD19 CAR T-cell therapy demonstrated a high safety profile and efficacy. Grade 3 neutropenia or thrombocytopenia toxicity was observed in three patients and grade 4 in seven patients. The median time for neutrophil recovery was 12 days (1 to 24 days), and 14 days (0 to 30 days) for platelet recovery. Non-hematological toxicities were mild, including fever in three patients, grade 1 liver dysfunction, and hypertension in one patient. Cytokine release syndrome (CRS) was observed in nine patients, with only one case of grade 3 severity managed successfully with steroids. The therapy achieved a 100% response rate, with 60% of patients attaining molecular MRD-negative complete remission and the remainder achieving hematologic complete remission, with a 12-month OS rate of 45.0% and a 12-month LFS of 46.7%. Nonetheless, relapse, predominantly characterized by CD19-negative phenotypes, was a common occurrence within six months post-treatment.

Conclusion: CD19 CAR T-cell therapy is a promising and manageable treatment for relapsed CD19-positive t(8;21) AML, offering a potential new strategy for disease remission with a manageable safety profile. It also highlights the importance of maintenance therapy in sustaining remission and improving long-term outcomes.

[1] Qu C, Li Z, Kang L, Wang Y, Dai H, Yin J, et al. Successful treatment of two relapsed/refractory t(8;21) acute myeloid leukemia patients by CD19-directed chimeric antigen receptor T cells. Bone Marrow Transplant. 2019;54:1138-40.