Potential benefits of using a different donor for transplantation consolidation after donor-derived CD7 CAR T.

Abstract

6536 Background: Stem cell transplantation (SCT) is often used in patients with relapsed or refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) after CD7 CAR T therapy, in order to consolidate efficacy or promote immune reconstitution to reduce the risk of infection. Previous studies have shown that consolidatory SCT may be able to prolong the survival of patients after CD7 CAR T. However, infections after SCT raise concerns. Here, we explored optimization strategies for SCT consolidation after newly HLA-matched donor-derived CD7 CAR T therapy in r/r T-ALL patients. Methods: This is a retrospective analysis of SCT consolidation following donor-derived CD7 CAR T therapy, based on a phase 1 trial (ChiCTR2000034762) and a phase 2 trial (NCT04689659) approved by the Institutional Review Board (IRB) of Beijing Goboard Boren Hospital, and a phase 1/2 trial (NCT06316427) approved by the IRB of Beijing Goboard Hospital. The analysis was aimed to evaluate the impact of using different donors for CAR T therapy and the subsequent SCT, compared to using the same donor. Results: A total of 19 patients were included in this analysis, including four from the phase 1/2 trial who used different donors for CAR T therapy and SCT consolidation (Group A), and 15 patients who used the same donor for CAR T therapy and SCT consolidation (Group B, 7 from the phase 1 trial and 8 from the phase 2 trial). The median age of the 19 patients was 11 (range 2-43). 16 patients (84%) were male, and three (16%) were female. The median interval from CAR T cell infusion to stem cell infusion was 32 days (range, 26-34) for group A, and 39 days (range 32-48) for group B. After stem cell infusion, all patients in group A had no detectable CAR T cells in the peripheral blood. However, in group B, six of the 13 patients evaluated had detectable CAR T cells in the peripheral blood, whereas the other seven did not. Within three months after stem-cell infusion, no patients in group A had CMV or EBV activation, while nine patients (60%) in group B had CMV or EBV activation. Two patients (50%) in group A and 10 patients (67%) in group B had any type of viral activation. Compared to group B, patients in group A tended to have a higher chimerism rate in the peripheral blood at two months and in the bone marrow at three months after stem cell infusion. Conclusions: In post-CD7-CAR patients, the risk of viral activation (especially CMV/EBV activation) after SCT using the same donor as CAR T was high. This may be partly related to the persistence of CAR T cells after SCT. The results showed that using a different donor from CD7 CAR T for subsequent SCT may contribute to the timely clearance of CAR T cells from patients and simultaneously reduce the rate of CMV/EBV activation after stem cell infusion. In addition, the chimerism rate was slightly increased at some time points. These results will be further evaluated in an ongoing phase 1/2 study at our center. Clinical trial information: NCT04689659 , NCT06316427 , ChiCTR2000034762 .