First report of the GIMEMA INO-first multicenter observational study analyzing infective and non-infective complications in patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with inotuzumab ozogamicin.

Abstract INTRODUCTION. Based on the results of the phase III study INO-VATE, Inotuzumab ozogamicin (INO) has been approved as single agent for the treatment of adult patients with relapsed/refractory CD22 positive B-cell acute lymphoblastic leukemia (B-ALL) and for adult patients with Philadelphia positive (Ph+) ALL who previously failed the treatment with at least one TKI inhibitor. However, even if INO is extensively used in clinical practice, very few real-life data are available regarding the toxicity profile of this drug. METHODS. We report preliminary data from GIMEMA-INO-FIRST trial, a retrospective, observational clinical-epidemiological study (ClinicalTrials.gov ID NCT06025682). The study collects data from about 20 Hematologic Centers of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) Group treating B-ALL patients with inotuzumab-ozogamicin (INO) over the last 5 years (2018-2023), according to the authorized indications and not included in interventional clinical trials (randomized or not randomized). The main objective of this study is to analyze, in a real-life setting, the infective and non-infective adverse events (AEs) in patients with B-ALL treated with salvage INO immunotherapy. The AEs have been graded on a scale of 1 to 5 according to the Common Toxicity Criteria for AEs (CTCAE) Version 5.0. RESULTS. A total of 115 patients were enrolled in the study, of whom 98 (males 63%) are currently evaluable for this preliminary analysis. The median age was 57 years (range, 21–80 years), and 78% of patients had a performance status of 0 or 1. The 77% of cases had a relapsed and 23% a refractory B-ALL. The median pre-INO bone marrow (BM) blasts was 35%. Ph-positive ALL cases were 34% (33/98). INO was administered at the standard dose according to the data sheet, and most patients (80%) received two or more cycles (C) of INO. The overall response rate (ORR) to INO therapy was 66%, with a complete response (CR) rate of 63%. Death during INO treatment was only 2% and treatment discontinuation due to toxicity occurred in only 2 cases (2.8%). Of the 98 patients who received INO, 45 (46%) received a subsequent allogeneic transplantation-SCT (donor: sibling 27%, haplo 31%, MUD 42%). A total of 13 Grade > 2 AEs were reported during INO treatment (6 in C1, 5 in C2, 1 in C3, and 1 in C4) that occurred in 8.2% (8/98) of patients. Specifically, the following grade 2 or more AEs were reported: 3 FUO (3/3 grade 2), 3 pancytopenia (2/3 grade 3 and 1/3 grade 4), 2 intestinal mucositis (1/2 grade 2 and 1/2 grade 3), 1 pneumonia (grade 3), 1 pancreatic toxicity (grade 3), 1 hepato-renal syndrome (grade 4), 1 liver toxicity (grade 2), and 1 oral mucositis (grade 2). After SCT, a VOD was reported in 19% of cases (8/45). CONCLUSIONS. These preliminary data, which will undergo thorough analysis in the coming months, showed that significant (grade 2 or higher) infectious and non-infectious AEs were uncommon in patients with relapsed or refractory B-ALL who received INO salvage therapy. These AEs occurred in only 8.2% of patients and resulted in treatment discontinuation in only 2.8% of cases. These findings support the use of INO as a suitable bridging therapy to SCT or to other cellular immunotherapies.