BLINATUMOMAB + DONOR LEUKOCYTE INFUSIONS (DLI) CAN BE USED TO PREVENT THE RELAPSE OF ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION (HCT)

Abstract

Chimeric antigen receptor (CAR) T-cell therapy is a choice for ALL relapsed post-HCT but is hindered by cost and the required lengthy washout period, emphasizing the need for new strategies to prevent relapse. For those at high relapse risk due to disease characteristics or high pre-HCT residual disease levels, blinatumomab post-HCT to guide the donor lymphocytes could be an effective option to eliminate MRD before relapse occurs. The objective of this study is to evaluate the use of blinatumomab maintenance in pediatric patients with high-risk ALL undergoing HCT. Methods: Children with high-risk ALL received Blinatumomab via a portable pump initiated at discharge from HCT. The full maintenance dose began after a single steroid pre-medication. Results : Eleven patients, 5 females, median age 8 years (1-12), were included. Nine had haploidentical HCT; 10 had pre-HCT blinatumomab. Six were in first remission after primary refractory disease, others in ³ 2nd remission. Five showed 0.01%-0.8% pre-HCT MRD. Conditioning regimens included 1200cGy TBI with fludarabine (5) or etoposide (6). Median CD34+ cell dose was 6x106/kg (4-10x106/kg). Median day of neutrophil engraftment was D+18 and blinatumomab start, D+26 (22-323), median cycles post-HCT: 3 (1-6), interval between cycles: 14 days (13-44). At blinatumomab start, 8 remained on cyclosporine, 2 were reducing steroids. Specific therapies included dasatinib (Ph+), venetoclax, and trametinib (RAS) in 3 patients. Six without GVHD had concurrent DLI to boost T-cell recovery, median 2 doses/patient, 1x106/kg CD3+ (1x105-5x106/kg). Median lymphocytes at 1st blinatumomab cycle: 480 CD3/μL (80-2,450). Adverse events involved hematologic toxicity, viral reactivations (herpes viruses, CMV, BKV, COVID), and fever in 4 patients without signs of cytokine release syndrome; infusions werw paused 24h and resumed at slower rate. No severe infections reported. A Down's syndrome patient had a seizure, causing brief dose reduction. All received IgG replacement. Eight developed acute GVHD, none beyond MAGIC grade II; 4 had mild chronic GVHD. Three relapsed, one recovered with CAR T-cell therapy, two died from disease; one died in remission from unidentified pneumonia. At 20 months median follow-up (2-38), 7/11 extremely high-risk ALL patients remain in remission post-allogeneic HCT with blinatumomab. Conclusion: The study highlights that blinatumomab maintenance post-HCT in pediatric ALL as effective and safe. Despite tough cases, outcomes are promising. Manageable adverse events confirm feasibility as a possible alternative where CAR T-cell access is limited. Adding DLI may enhance therapeutic effects. These results support using blinatumomab maintenance as a strategy to reduce pediatric ALL relapse risk post-HCT, deserving further exploration in larger prospective trials.