Inotuzumab ozogamicin as salvage therapy for refractory/relapsed B-cell acute lymphoblastic leukemia following the failure of chimeric antigen receptor T cell therapy and allogeneic hematopoietic stem cell transplantation

Abstract Although inotuzumab ozogamicin (InO) has been approved as an effective agent for patients with refractory/relapsed (r/r) B-cell acute lymphoblastic leukemia (B-ALL), data on safety and efficacy in the context of post chimeric antigen receptor (CAR)-T cell therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) relapse are lacking. We report a retrospective study assessing the safety, toxicities, and outcomes of InO in three heavily treated r/r B-ALL patients who particularly relapsed after both CAR-T therapy (three patients received sequential CD19 and CD22-targeted CAR-T, universal CD19-targeted CAR-T, and bispecific CD20/CD22-targeted and universal CD19-targeted CAR-T therapy respectively) and allo-HSCT. Results showed that all of three patients achieved bone marrow remission with negative minimal residual disease (MRD) after the first InO cycle; of note, one patient with multiple extramedullary involvement before InO treatment experienced a remarkable tumor regression evaluated by PET/CT images. All patients completed two cycles of InO. With a median follow-up of 14.5 months, the 12-month overall survival (OS) rate was 100%. Adverse events were manageable, with no unexpected toxicities observed. Moreover, no sinusoidal obstruction syndrome was developed in any of patients during the whole course of InO therapy and beyond. However, two out of them relapsed 8 and 9.5 months after the InO initiation, respectively. In conclusion, InO is a well-tolerated, effective regimen for patients with B-ALL who relapse after prior CAR-T therapy and allo-HSCT, despite the long-term progression free survival needs improving.