Anti-CD19 CAR T-Cell consolidation therapy combined with CD19+ feeding T cells and TKI for Ph+ acute lymphoblastic leukemia.

We conducted a single-arm, open-label, single-center phase I study (Clinicaltrials.gov NCT03984968) to assess the safety and efficacy of multicycle-sequential anti-CD19 CAR T-cell therapy in combination with autologous CD19+ feeding T cells (FTCs) and TKI as consolidation therapy in patients under the age of 65 years with de novo Ph-positive CD19+ B-ALL who are not eligible for allo-HSCT. Participants were given induction chemotherapy as well as systemic chemotherapy with TKI. Afterward, they received a single cycle of CD19 CAR T-cell infusion and another three cycles of CD19 CAR T-cell and CD19+ FTC infusions, followed by TKI as consolidation therapy. CD19+ FTCs were given at three different doses: (2×106/kg, 3.25×106/kg, and 5×106/kg). The phase I results of the first 15 patients, including 2 withdrawals, are presented. Phase II research is still ongoing. The most common adverse events were cytopenia (13/13) and hypogammaglobinemia (12/13). There were no CRS above grade 2 or ICANS, or grade 4 nonhematologic toxicities. All 13 patients achieved CR, including 12 patients with CMR at the data cutoff on Mar 31, 2022. The RFS was 84% (95% CI, 66%-100%), and the OS was 83% (95% CI, 58%-100%) with a median follow-up of 27 months (7-57 months). The total number of CD19-expressing cells decreased with an increasing CMR rate. CD19 CAR T cells survived for up to 40 months, whereas CD19+ FTCs vanished in 8 patients 3 months after the last infusion. These findings merit further evaluation and could form the basis for the development of an allo-HSCT-free consolidation paradigm.