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)

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.