Real World Data of Inotuzumab Ozogamicin for Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia
Authors: Espinoza Marcela , Rodríguez Nicolás , Conte Guillermo , Samaniego Francisco , Lopez Miguel Nicolas , Aranguiz Natalia , Quinteros Nicolás , Astete Daniel , Carcamo Lucas , Guerrero Gonzalo , Flores Constanza , Huerta Ximena , Flores Yorman , Jerez Joaquin , Chandía Mauricio A , Valenzuela Jorge , Rojas-Vallejos Jorge , Cavada Gabriel 
Published: December 2024

Introduction: Inotuzumab Ozogamicin (InO) is a CD 22 monoclonal antibody that is covalently linked to calicheamicin, a potent cytotoxic agent that causes double-stranded DNA breaks and has shown activity in adults with RelapsedRefractory Acute Lymphoblastic Leukemia. (R/R ALL). There is a scarcity of real-world studies specially in Latin America. Objective: Our objective was analyzing the outcomes of Chilean patients treated with this drug. Primary endpoints: Complete Response (CR), Minimal Residual disease (MRD). Secondary Endpoints: Overall Survive (OS), Progressive Free Survival (PFS), rate of Hematopoietic Stem Cell Transplant (HSCT) after InO. Methods: We obtained clinical records from 35 patients with R/R ALL, older than 15 years old, treated with InO from January 2018 to March 2024. Patients with altered hepatic profile or previous VOD/SOS were excluded. InO was used as monotherapy in 31 patients and mini-HyperCVAD-InO in 4 patients.

Results: 35 patients were included, 27 from private centers and 8 from public centers. 21 (60%) females. Median age at diagnosis 32-year-old (range 15-73), WBC 52.8 per mm3. Philadelphia (Phi) negative ALL in 25/35, Phi (+) 6/35, Lymphoid Blast Crisis 1/35 patient, Mixed-Phenotype Acute Leukemia (MPAL) 1/35, Burkitt Lymphoma-Leukemia phase 1/35, B-ALL t(8:22) 1/35. Mean PB blast cell 32. Mean Aspartate aminotransferase (AST) was 47.4 U/L. 20 patients relapsed and 15 refractory diseases. Flow cytometry: 48% was positive (mostly unreported) for CD 22 and 88,5% CD 19. Mean of cycles: 2, (1-4). Multivariate analysis was not significative for dismal outcome regarding blood cell count, age, gender or Phi (+).

CR/CRi was 77%, MRD was measured in 29 patients, 44% of them was &lt;0.01%. 16 patients received HSCT after InO and had a better median OS (23 vs 8.4 months, p=0.1). 7/35 patients received InO after HCST, 6 of them had refractory disease and died at the end of the study. Median time to transplant was 5.8 months. 77% had Myeloablative conditioning FLU TBI in 66%, 37.1% had Haploidentical HSCT and SOS was observed in 4 patients (8.5%), 2 in InO treatment and 2 in HSCT.

Mean OS from the use of the drug to death was 13.4 months, PFS 12.2 months, 5 patients received blinatumomab at some point of their treatment, there was no difference between two groups (p=0.02). The best results were seen in patients with CR/CRi1 with MRD negative (median OS 33.3 months). Relapsed had a better OS and PFS but not significative (p=0.2)

Conclusion: We present a local experience using InO, we observed similar OS and PFS than other reports. The best outcomes were seen in patients who achieved MRD negative and receive a SCT after InO. Limitations of study is the short time of following and limited number of patients.