Treatment of Adults with Relapsed/Refractory Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia with Blinatumomab in a Real-World Setting: Results from the Neuf Study

Background: Blinatumomab is approved in Europe for adult and pediatric patients (pts) with relapsed and/or refractory Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (R/R Ph- BCP-ALL), and for adult pts with minimal residual disease (MRD)-positive Ph- BCP-ALL. Prior to country-specific reimbursement, blinatumomab was made available to pts who met pre-specified criteria via an expanded access program: this included both adult and pediatric pts with a diagnosis of R/R Ph- BCP-ALL, R/R Ph+ BCP-ALL, or MRD-positive Ph-/Ph+ ALL. Here, we describe adults with R/R Ph- BCP-ALL enrolled in this retrospective observational study (NEUF) in specific European countries, with reference to their characteristics, blinatumomab usage and effectiveness. Methods: Eligible pts initiated blinatumomab in the expanded access setting between 1 Jan 2014 and 31 Dec 2016. Data were extracted from medical notes. Pts were followed from blinatumomab initiation until death, entry into a clinical trial, end of follow-up, or the end of the study period (30 June 2017), whichever occurred first. Adverse events were reported separately, according to local regulations. Calculation of percentages excluded patients with missing data, unless otherwise indicated. Results: In total, 253 adult pts were enrolled (113 in Italy, 45 in Russia, 53 in Spain, 33 in France, and 9 in the UK): prior to blinatumomab initiation 106 (43%) had a diagnosis of R/R Ph- BCP-ALL, 32 (13%) had R/R Ph+ BCP-ALL, 109 (44%) had MRD positive ALL (either Ph- or Ph+), and 6 (2%) had diagnosis data missing. Among R/R Ph- BCP-ALL pts (n=106), 47% were female and median age was 36.5 years (interquartile range [IQR]: 24.0, 52.0). Forty-one percent (n=43) had prior allogeneic hematopoietic stem cell transplant ((HSCT). The median number of prior salvage therapies was 1.0 (range: 0.0, 2.0). At blinatumomab initiation, 64 (60%) experienced a relapse and 42 (40%) were refractory. At least half (53%, n=54) of pts were treated with pre-phase and 89% (n=93) with pre-medication with dexamethasone. Within two cycles of blinatumomab, 54 (51%) pts achieved complete remission (CR) with full/partial/incomplete recovery of peripheral blood counts. Among patients achieving CR and who had evaluable MRD (n=33), 85% (n=28) had MRD response (16 with non-detectable MRD and 12 with MRD