Inotuzumab ozogamicin following allogeneic hematopoietic stem cell transplantation successfully rescued relapse of CD19‐negative acute lymphoblastic leukemia after CAR‐T cell therapy

Abstract

To the Editor Anti-CD19 chimeric antigen receptor (CAR)-T-cell therapy is one of the most promising treatment options for patients with relapsed/refractory B-cell precursor (BCP)-acute lymphoblastic leukemia (ALL).1–3 Approximately 30%–60% of patients experience relapse after CAR-T cell therapy, largely due to poor longevity of CART cells and loss or downregulation of CD19 expression by leukemic cells.4,5 The survival rate of these patients is extremely poor; however, there is no consensus regarding the best salvage treatment.1 Here, we report a 5-year-old boywith BCP-ALL harboring the ETV6RUNX1 rearrangement. He experienced a second bone marrow (BM) relapse 1 year after cord blood transplantation using a myeloablative conditioning regimen consisting of melphalan (180 mg/m2) and fractionated total body irradiation (TBI; 12 Gy) in the second minimal residual disease (MRD)-negative complete remission (CR), defined as <0.01% by flow cytometry. He was enrolled in the phase II, multicenter, global trial of CAR-T cell therapy (the ELIANA trial),3 resulting in the thirdMRD-negative CRwithout complications (except for B-cell aplasia). Unfortunately, he experienced a third BM relapse 1 year later at the age of 12. Since leukemic blasts were negative for CD19 but positive for CD22, he received Inotuzumab ozogamicin (InO)monotherapy. The off-label use of InO was approved by the Patient Safety Unit, Kyoto University Hospital. The patient’s family provided written informed consent before administration. Following one cycle of InO (0.8 mg/m2 on day 1, and 0.5 mg/m2 on days 8 and 15), he achieved a fourth MRD-negative CR. After a second cycle of InO (0.5 mg/m2 on days 1, 8, and 15), he underwent T-cell replete haploidentical BMT from his HLA-6/8 allele-matched father, using a reduced-intensity conditioning (RIC) regimen consisting of fludarabine (120 mg/m2), cytarabine (6 g/m2), and melphalan (180 mg/m2). Tacrolimus (TAC), shortterm methotrexate, prednisolone, and rabbit anti-thymocyte globulin (2.5 mg/kg) were used for graft-versus-host disease (GVHD).6 Ursodeoxycolic acid, low molecular weight heparin, and antithrombin