Safety and Efficacy of Blinatumomab- Real World Data
Authors: Apel Arie , Ofran Yishai , Ram Ron , Levi Itai , Zektser Miri , Koren-Michowitz Maya 
Published: October 2019

Abstract
Background:
Despite improvement in survival of newly diagnosed adult ALL, the results of relapsed/refractory disease are still poor, with long term survival of < 10%. Blinatumomab, a bispecific monoclonal antibody directed against CD19/CD3 show clinical activity against relapsed/refractory B-ALL as well as in MRD positive patients. Given in a continues 28 days infusion, and its unique side effects profile are potential drawbacks to using blinatumomab in routine care. We report our initial experience with blinatumomab in widespread use, in real-world experience.
Methods:
Data from adult patients with B-ALL/B-LBL treated with blinatumomab in 4 hospitals in Israel was collected. Blinatumomab was given at the standard dose of 9 mcg/day in the first week of the first cycle, and 28 mcg/day thereafter for 28 days cycles, repeated every 6 weeks. Safety data including cytokine release and neurological symptoms was collected. Efficacy outcome included overall and complete response rates, overall survival, and leukemia free survival.
Results:
13 patients are included in this analysis, median age 51.6 years (range 28.9-80.3) 7 male and 6 females. Diagnoses were B-ALL in 10, Ph+ B-ALL in 2, and B-LBL in 1 patient. Median time from diagnosis to blinatumomab treatment was 9.8 months (range 3.4-26.3), and 12/13 patients received blinatumomab for hematological relapse with 1 patient receiving treatment due to severe fungal infection and inability to continue standard chemotherapy or proceeding to SCT. Four patients (30.7%) received blinatumomab after allogeneic SCT. Three patients (23%) had CNS disease at the time of relapse. Blinatumomab was given as first salvage in 7, and after prior salvage in 6 patients. Median number of blinatumomab cycles were 1 (range 1-6), and patients spent on average 18.9 days in-hospital, and 18.8 days as outpatients during the treatment period.
Response was evaluable in 12 patients with 5/12 patients achieving CR and 1 patient maintaining a previously achieved CR. CR was achieved in 2/2 Ph+ ALL patients, 1/4 patients relapsing after SCT and 1/3 patients with CNS disease at relapse. Following blinatumomab, 4 patients received allogeneic SCT, 1 in CR, 2 failing blinatumomab and entering CR after CAR-T therapy within a clinical trial and 1 after combination chemotherapy.
Non-hematological side effects consisted of neurological symptoms in 1 (grade 2), GI symptoms in 1 (grade 3), infection in 1 (grade 3) and cytokine release syndrome in 3 patients (2-grade 2; 1-grade 4).
At a median follow up of 13.3 months (range 1-20.6), 8 (62%) patients are alive, 6 (46%) in CR. Reasons for death included infection in 3 and disease progression in 2 patients. No patient died during blinatumomab administration. Median LFS is 8.7 months and median OS was not reached.
Conclusions:
The current cohort show a slightly higher CR rate and similar OS compared to the TOWER and ALCANTARA trials. Treatment with blinatumomab was safe, with manageable toxicity profiles. This, however, was achieved at a cost of prolonged hospitalizations in the majority of patients.

Disclosures
Ofran: Novartis: Other: Served on a Novartis advisory board.