Work

Safety of Addition of Inotuzumab Ozogamicin to One Alkylator-Containing Reduced-Intensity Conditioning Regimen in Hematopoietic Cell Transplantation (HCT) for Patients with Acute Lymphoblastic Leukemia and CD22 (+) Aggressive Lymphoid Malignancies: A Prospective Trial

Year: 2025

Type: article

Abstract: Background Inotuzumab ozogamicin (INO) has been associated with an increased risk of veno-occlusive disease in patients receiving hematopoietic cell transplantation (HCT). Risk factors included the use a two-alkylator containing regimens, prior use of INO and elevated liver function tests. In this study, we prospectively studied the safety of INO in patients receiving HCT after one-alkylator containing conditioning. Patients and Methods The eligibility criteria were age 18-70 years with CD22(+) disease requiring HCT. In addition, patients were required to have adequate liver function and a 6/6 HLA-compatible sibling donor or an HLA-A, HLA-B, HLA-C, and DRB1-matched unrelated donor (MUD) INO was infused intravenously (IV) on day -13 outpatient, at a dose of 0.3 mg/m 2 . Fludarabine 30 mg/m 2 IV daily on days -5 to -2 and melphalan 140 mg/m 2 IV on day -2 were given prior to HCT. Tacrolimus and methotrexate were used for graft versus host disease (GVHD) prophylaxis. Results The study included 9 patients with a median age of 54 (range, 27-64) years. Disease types included B-ALL (n=7 [6 in first complete remission (CR1) and 1 in CR2]) and lymphoma (n=2; 1 with Richter's transformation and 17p deletion). Risk factors for patients with ALL included the presence of TP53 mutation with complex cytogenetics (n=3), KMT2A mutation (n=2), and IKZF1 mutation (n=1). Key prior therapies in ALL patients included blinatumomab (n=5) and INO (n=5). The maximum doses of INO received prior to HCT were 1.2, 1.5, 2.7, 2.7, and 2.7 mg/m 2 . Six (67%) received their transplants from sibling donors and 3 (33%) from MUDs. All patients experienced 100% donor engraftment. Neutrophil counts recovered to more than 0.5 × 10 9 /L a median of 12 days after HCT (range, 9-19 days). Platelet counts recovered to more than 20 × 10 9 /L after a median of 13 days (range, 0-27 days). None of the treated patients developed veno-occlusive disease. Treatment-related mortality at 2 years was 14%. With a median follow-up of 13 months (range, 1-36), the 2-year overall survival and progression-free survival rates were 60% and 62%, respectively. Two patients experienced a relapse: 1 with initial primary induction failure with TP53 mutation and 1 with KMT2A mutation who had extramedullary sarcoma at relapse after HCT. The 2 other patients with TP53 mutation and complex cytogenetics remained alive and in molecular remission at 18 and 36 months. The incidence of grade II-IV GVHD was 48%. One patient had chronic extensive GVHD. Conclusions Our conclusions are limited by the small number of patients due to slow accrual. However, our data suggest that INO is safe when combined with a melphalan plus fludarabine HCT conditioning regimen. The survival outcomes are encouraging and need to be validated in a larger number of patients. Currently, post-transplant cyclophosphamide has been implemented to lessen the risk of GVHD.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.287