PB1674 BLINATUMOMAB AND INOTUZUMAB‐OZOGAMICIN: A “REAL LIFE” EXPERIENCE OF IMMUNOTHERAPY IN REFRACTORY/RELAPSED B‐CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: M. Sciumè, J. Rosa, A. Freyrie, R. Cassin, G. Reda, L. Baldini, N.S. Fracchiolla
Journal: HemaSphere (2019)

Background: The prognosis of refractory/relapsed B acute lymphoblastic leukemia (R/R B‐ALL) still represents a clinical challenge. In this setting, therapy with the bispecific T cell engager blinatumomab or the anti‐CD22 antibody‐drug conjugate inotuzumab‐ozogamicin (IO) showed promising results. Aims: We aimed to describe our clinical experience in the use of blinatumomab and/or IO in a monocentric series of relapsed/refractory R/R B‐ALL. Methods: Adult patients with R/R B‐ALL treated with blinatumomab and/or IO for disease reappearance (morphologic or molecular) were selected from the institutional database. Results: We identified 13 R/R B‐ALL patients who received blinatumomab and/or IO for disease relapse. At diagnosis median age was 61 years (23‐75); 9 patients had a very‐high‐risk disease (4 Philadelphia chromosome–positive‐Ph+ ALL) and 4 patients a standard risk ALL. Five cases received sequentially blinatumomab and IO, while 6 patients were treated with only blinatumomab and 2 with only IO. Blinatumomab was given as continuous IV infusion at a dose of 28 μg/m 2 /d for 4 weeks, with a 2 week break. IO was given IV at a dose of 1.8 mg/m 2 for the first cycle and then 1.5 mg/m 2 , divided in three weekly doses, every 3‐4 weeks. At blinatumomab start, median number of prior therapy lines was 2 (1‐5). Ph+ ALL patients were treated with multiple tyrosine kinase inhibitors, 1 received prior allogeneic stem cell transplantation (allo‐HSCT). Median number of blinatumomab cycles was 3 (1‐5). After 2 cycles 10 patients achieved a complete remission (CR); 8 of them were in complete cytofluorimetric or molecular remission. The remaining one patient was a Ph+ ALL who developed a progressive disease with lymph‐nodes involvement, without bone marrow morphologic or molecular evidence of ALL. Four patients experienced a cytokine release syndrome grade 1/2, while 2 patients experienced a grade 3 neurological toxicity. In 2 cases blinatumomab was used as bridge to transplant. Relapse occurred in 5 cases after CR achievement: 2 molecular relapses (1 after allo‐HSCT) and 3 morphologic bone marrow relapse. CD19 expression was lost in 2 cases. Median progression‐free‐ survival (PFS), time to next treatment (TTNT) and overall survival (OS) from blinatumomab start were 268, 278, 393 days, respectively. Three patients died due to progressive disease and all of them were exposed to IO salvage treatment after blinatumomab. Regarding the 7 patients treated with IO, median number of prior therapy lines was 4 (3‐8), including blinatumomab in all cases except one. The median IO cycles was 2 (1‐6). Only one patient experienced progressive disease during IO, the remaining 6 patients achieved a morphologic CR since first cycle. Negative cytofluorimetric or molecular disease was achieved in 2 patients. IO therapy was safe: one patient had a QT prolongation during concomitant use of IO and amiodarone, while a grade 2 transaminases elevation was seen in another case. Two patients received IO as bridge to transplant; three cases relapsed after a CR achievement and 2 of these relapses occurred after allo‐HSCT. Median PFS, TTNT and OS were all 58 days. Summary/Conclusion: This monocentric survey underlies the feasibility and efficacy of immunotherapy in the setting of R/R B‐ALL, also in a sequential use mode.