CAR T-Cell Therapy in B-ALL Patients

Autologous T Cell Therapy in B-ALL

• Five patients with relapsed B-ALL received autologous T cells modified with a CD19-specific dual-signaling CAR (19-28z).
• All patients with either persistent morphological disease or minimal residual disease (MRD+) at the time of T cell infusion experienced rapid tumor eradication and achieved MRD-negative complete remissions.
• Infusion of CAR-modified T cells was well tolerated, although significant cytokine elevations were observed in patients who had active disease, necessitating lymphotoxic steroid therapy.
• Cytokine levels correlated directly with tumor burden at the time of CAR T cell infusion; lower tumor burden resulted in an improved side-effect profile.
• One patient, relapsed post-CAR therapy and ineligible for additional allogeneic hematopoietic stem cell transplant (allo-HSCT), showed persistent expression of CD19 and sensitivity to the CAR-modified T cells, indicating potential for additional CAR infusions.

Efficacy and Safety of 19-28z CAR T Cells

• The therapy demonstrated marked anti-tumor efficacy, rapidly achieving MRD-negative status, which improves prognosis by making patients eligible for allo-HSCT.
• Without CAR therapy, two patients would have been ineligible for transplantation, while another two would have proceeded with poor prognosis due to remaining MRD.
• Cytokine-mediated toxicities, previously a concern, were minimized by infusing T cells in patients with lower disease burden either in MRD+ setting or soon after initial salvage chemotherapy.

Treatment Protocol and Patient Cases

• Patients underwent leukapheresis to obtain peripheral blood mononuclear cells (PBMCs), which were activated and transduced with the 19-28z receptor using dynabeads.
• Two patient case highlights:
  • MSK-ALL01: A patient treated with preconditioning chemotherapy followed by CAR T cell infusion achieved MRD-negative status and subsequently underwent allo-HSCT.
  • MSK-ALL06: A female patient relapsed after prior consolidation therapies; CAR T cells were administered, leading to MRD-negative status and successful allo-HSCT after infection resolution.

Persistence and Effectiveness Monitoring

• The persistence of the 19-28z CAR-modified T cells was monitored through flow cytometry in both peripheral blood and bone marrow.
• Responses to CD19 were assessed through serial samples, tracking the presence of malignant cell populations versus normal B cells using deep sequencing techniques.
• Data showed a significant reduction in malignant IgH rearrangements post-treatment indicative of treatment efficacy.

Conclusion

• The 19-28z CAR-modified T cell therapy shows promise as a viable treatment option for relapsed/refractory B-ALL, effectively bridging patients to potentially curative allo-HSCT with profound molecular remissions.

Explore the results of a study involving 5 patients treated with autologous T cells expressing a CD19-specific CAR for relapsed B-ALL. This quiz covers the effects of the therapy on persistent morphological disease and minimal residual disease (MRD), highlighting the rapid tumor eradication and remission achieved.