Hagop m. Kantarjian¹, Anthony s. Stein², Ralf c. Bargou³, Carlos Grande⁴, Richard a. Larson⁵, Matthias Stelljes⁶, Jonathan Benjamin⁷, Catherine Jia⁸, Max s. Topp⁹

¹TX, 1The University of Texas MD Anderson Cancer Center, Houston,, ²City of Hope, Duarte,CA, ³Comprehensive CancerCenter Mainfranken, Universitätsklinikum Würzburg, Würzburg, Germany, ⁴Hospital Universitario12 de Octubre, Madrid, Spain, ⁵University of Chicago, Chicago, Illinois, ⁶University Hospital of Münster, Münster, Germany, ⁷Amgen Inc., Thousand Oaks, CA, ⁸Amgen Inc., South SanFrancisco, CA, ⁹Medizinische Klinik undPoliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany

Objective:Treatment options for older pts with R/RALL are limited. Blinatumomab is a bispecific T-cell engager (BiTE^®) antibody construct that directs cytotoxic T cells to CD19-expressing B cells,and is approved in the US for treatment of Ph- R/R ALL. In two phase 2 adult studies of blinatumomab (Topp MS, et al. J Clin Oncol. 2014;32:4134-40; ToppMS, et al. Lancet Oncol. 2015;16:57-66), 69%and 43%, respectively, achieved complete response (CR) or CR with partial hematologic recovery (CRh*). Wereport pooled data for the combined subsets of older pts (≥ 65 yrs). Method:Pts with R/R B-precursor ALL received open-label blinatumomab by continuousIV infusion (4 weeks on/2 weeks off). Pts achieving CR or CRh* after two cyclescould receive three consolidation cycles. Response was assessed by bone marrow aspiration. CR required blasts <5%, ANC>1000/μL and platelets >100,000/μL. CRh* required blasts <5%, ANC>500/μL and platelets >50,000/μL. Minimalresidual disease (MRD) was detected by ASO-PCR of Ig heavy chain loci. Result: 36 older pts (median age 70 yrs, range 65-79) receive dblinatumomab for amedian (range) of 2 (1-6) cycles. 20 (56%) pts achieved best response ofCR/CRh* within two cycles, including 14 (39%) CR and 6 (17%) CRh*. Among responders, 12 (60%) had complete MRD response and 4 other pts had detectableMRD but < 10‑4. With median follow-up of 18.2 months, median (range) relapse-free survival for responders was 7.4 (1.0-34.0) months. With medianfollow-up of 29.4 months, overall survival was 5.5 (0.3-41.9) months. 10(28%) pts were alive at last follow up; 6 in remission. 2 (10%) responders underwentallogeneic HSCT after blinatumomab. Treatment-emergent adverse events (AE)CTCAEgrade ≥ 3 were reported for 31 (86%) pts, most commonly febrileneutropenia (22%) and neutropenia (19%). Neurologic AE occurred in 26 (72%)pts, including grade ≥ 3 events for 28%. 1 (3%) pt had grade ≥ 3 cytokinerelease syndrome. Of7 fatal AEs, none were considered related to treatment. Conclusion: Older pts (≥ 65 yrs) with R/R ALL in two phase 2studies of open-labelblinatumomab had similar treatment responses and tolerability as pts in theoverall study populations.

Key Words: blinatumomab  older patients  B precursor acute lymp-hoblastic leukemia