Inotuzumab Ozogamicin (IO) Is An Effective Salvage Therapy That Allows for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Remission in Patients with Advanced Acute Lymphoblastic Leukemia (ALL)
Authors: Kebriaei Partow , Wilhelm Kaci , Ravandi Farhad , Saliba Rima M. , De Lima Marcos , Ciurea Stefan O , Worth Laura L. , O'Brien Susan , Thomas Deborah A. , Champlin Richard , Kantarjian Hagop M. 
Published: October 2019

Abstract
Abstract 3102
No highly effective salvage therapy exists for patients with relapsed acute lymphoblastic leukemia (ALL). Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody attached to calicheamycin and targets B lymphocytes in early stages of development. A 56% overall response rate was noted in a Phase I study of single agent IO in patients with refractory ALL (Jabbour ASCO 2011), enabling subsequent transplant in remission in a relatively large number of patients. Of note, in the year prior to the availability of IO, we consulted on 13 patients will ALL beyond second remission and transplanted 5 (38%), and after the availability of IO, we consulted on 41 patients and transplanted 27 (67%). Methods: We describe our findings in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) following treatment with IO between June 2010 and May 2011. IO was administered at 1.8 mg/m2 IV every 3 weeks. Results: 19 patients with median age 32 years (range 5–60) received an allogeneic matched sibling (n=6), matched unrelated donor (n=8), mismatched unrelated donor (n=4), or cord blood HSCT (n=1) in complete remission (CR) (n=2), CR without platelet recovery (n=14), and active disease (n=3); 10 patients were MRD negative at time of HSCT as determined by multiparameter flow cytometry. Patients had received 2 (n=3), 3 (n=9), 4 (n=4), 5 (n=2), or 6 (n=1) lines of salvage therapy prior to HSCT, including 3 patients who had received a prior allogeneic HSCT; IO was the last agent in 17 patients (2 patients refractory to IO received other therapy prior to HSCT). Patients received 1 (n=1), 2 (n=9), 3 (n=6), 4 (n=2), or 5 (n=1) courses of IO a median of 35 days (range 18–69) prior to transplant conditioning with busulfan (Bu) and colafarabine (Clo) (n=8), BuClo+ thiotepa (TT) (n=4), fludarabine (Flu) and melphalan (Mel) (n=1), FluMelTT (n=3), or etoposide and total body irradiation (TBI) (n=3); GVHD prophylaxis was tacrolimus-based for all patients, with post-HSCT cyclophosphamide added for patients receiving mismatched unrelated donors. With a median follow-up of 3 months among surviving patients (0.6–8.2), overall and progression-free survival is 59% at 3 months. There were 11 deaths, 6 from relapse, 4 from multi-organ failure involving VOD, and 1 from pneumonia. Transient liver enzyme elevations were noted in all of the patients, with 26% (n=5) patients developing VOD. The development of VOD was associated with greater lines of prior therapy prior to HSCT (3–5 lines prior salvage therapy, including 2 patients who had a prior allo-HSCT) and more intense transplant conditioning regimens (4 of the 5 patients received BuCloTT or FluMelTT). Conclusions: IO is an effective salvage therapy in patients with advanced ALL, allowing more patients to receive HSCT with encouraging response rates. Longer follow-up is needed to more completely assess disease control. Using reduced intensity HSCT conditioning regimens and avoiding multiple lines of prior therapies may result in less hepatic toxicity.

Disclosures:
O'Brien: Pfizer: Consultancy. Kantarjian:Pfizer: Research Funding.