P402: INOTUZUMAB OZOGAMICIN TREATMENT IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY PHILADELPHIA CHROMOSOME-NEGATIVE CD22-POSITIVE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA: A REAL-LIFE FRENCH STUDY

Abstract

Background: Inotuzumab ozogamicin (InO) is an antibody–drug conjugate approved in the US and the European Union for relapsed and refractory (R/R) CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL). InO was approved based on the results of the Phase 3 INO-VATE trial where significantly higher rate of complete or incomplete remission and higher probability of bridge to allogeneic hematopoietic stem cell transplant (HSCT) were observed in the InO arm as compared to standard chemotherapy arm. Real-life studies of InO use in adults with R/R BCP-ALL are scarce, notably including patients previously exposed to blinatumomab antibody therapy. Aims: This retrospective study was designed to provide a description of the characteristics and outcome of InO treated adult patients with R/R Philadelphia chromosome negative (Ph-) BCP ALL in real practice in France. Methods: This was a cohort-based, retrospective, multi-center, French observational study collecting patients’ data receiving InO between 15 March 2018 and 30 November 2019. All patients received EMA approved fractionated dosing with InO administered intravenously on days 1, 8, and 15 of each 28-day cycle. Median InO cumulative dosing was 1.8, 3.3 and 5.2 mg/m2 after 1, 2 and 3 cycles, respectively. Safety includes treatment related AEs reported in medical records and all causes of death related or unrelated to treatment. Results: Twenty-two patients (median age 38 years, range 18-71) received InO for refractory (n=4) or relapsed (n=18) disease. All received prior standard chemotherapy while 16 (72%) were previously treated with blinatumomab and 2 had prior allogeneic HSCT. Patients received a median of two InO cycles (range 1-6) as first or second and more salvage therapy in 7 and 15 patients, respectively. CD22 expression at last relapse was <70%, 70-90%, >90% or unknown % of medullar blasts in 6, 4, 11 and 1 patients, respectively. The median time between initial ALL diagnosis and InO initiation was 1.2 years (range 0.2-5.6) while the median delay between last relapse and InO initiation was 18 days (range 3-76). Overall response rate was 68% including 12 complete remission (CR) and 3 CR with incomplete hematologic recovery (CRi). Four were considered as treatment failure and 3 were not evaluated for medullar response. All responders achieved CR/CRi at the end of cycle 1. Eleven patients (50%) (10 responders and one not evaluated) were bridged to HSCT, using standard or sequential conditioning regimen in 9 and 2, respectively (figure 1). In terms of safety, 7 patients had at least one adverse event (5 patients had serious adverse events) reported as related to the treatment. Four patients experienced veno-occlusive disease (VOD) between 15 and 36 days following last InO administration. VOD occurred after bridged to HSCT in 3 of them. Causes of death were disease progression (7), infection (4), VOD (2), and multi-organ failure (2). In the study the median follow-up after InO initiation was 7 months (range 1-22) and seven patients were still alive at the end of study observation period. Summary/Conclusion: This retrospective cohort describes InO results in 22 R/R Ph- ALL patients who were highly pretreated and largely previously exposed to blinatumomab. Treatment was mostly limited to 1 or 2 cycles, and half of the patients were bridged to HSCT. The overall rate of CR/CRi as well as i) the proportion of patients bridged to HSCT and ii) treatment-related AEs and incidence of VOD were all comparable in real life practice with the observations made in the INO-VATE Phase III study. Figure 1: Swimming plots showing the outcome of patients after inotuzumab ozogamicin (INO) for R/R BCP-ALL. Keywords: B cell acute lymphoblastic leukemia, Targeted therapy, Real world data, Relapsed acute lymphoblastic leukemia