PS960 BLINATUMOMAB ‐ BASED THERAPIES IN CHILDREN AND ADULTS WITH MRD+ AND R/R B‐ALL, EXPERIENCE FROM A SINGLE CENTER (CIC 725)
Authors: Markova I. , Bondarenko S. , Bondarenko S. , Paina O. , Paina O. , Kozhokar’ P. , Kozhokar’ P. , Frolova A. , Frolova A. , Barkhatov I. , Barkhatov I. , Babenko E. , Babenko E. , Alyanskii A. , Alyanskii A. , Ekushov K. , Ekushov K. , Gindina T. , Gindina T. , Darskay E. , Darskay E. , Aubova B. , Aubova B. , Semenova E. , Semenova E. , Moiseev I. , Moiseev I. , Zubarovskaya L. , Zubarovskaya L. , Afanasyev B. , Afanasyev B. 
Published: June 2019

Background:The prognosis after frontline therapy in B‐ALL patients has improved due to monoclonal antibodies (CD20, CD19, CD22) and approximately 90% of patients achieve complete remission. In relapsed and refractory (R/R) and also in MRD+ B‐ALL outcomes are relatively poor. Disease‐free survival (DFS) in this cohort is 10–20%. Conventional chemotherapy is associated with high failure rate and significant toxicity. Immunotherapy with monoclonal antibodies and CAR‐T are the promising approaches.Aims:The aim was to evaluate the efficacy (frequency of responses, OS, DFS) and toxicity, especially neurotoxicity and cytokine‐release syndrome, of a bispecific monoclonal antibody blinatumomab in patients both children and adults with persistence of minimal residual disease (MRD+) or R/R B‐ALL.Methods:This study included 120 patients with high risk B‐ALL blinatumomab treated in 2013–2018, among them 14 pts (12%) with t (9;22), 10 (8%) with t (4;11), with MLL 11 (9%), 84 pts (70%) who were refractory to previous chemotherapy, 66 (30%) after allo‐HSCT from deferent type of donors. Children (0–18 y.o.) n = 55 (45%), and adults >18 y.o. n = 65 (54%). 63 pts (52%) had R/R ALL, 57 pts (48%) had MRD+, median days of follow up were 227 (18–720). Blinatumomab was applied as 28‐day cycles followed by a 14‐day off‐period before the start of the following cycle. Majority pts received one cycle (N = 94, 78%). In R/R ALL group dose was of 9 mcg/d during the first 7 days and afterwards 28mcg/d. Patients with weight less than 45 kg received 5 mcg/m2/d and 15mkg/m2/d accordingly. In MRD+ group dose was 15 mcg/m2/d.Results:The frequency of responses to blinatumomab was higher in MRD+ pts in comparison R/R ALL pts (85% vs 62 % p = 0.007). In MRD+ pts CR MRD− was achieved in 47 pts (82.5%), 10 pts (17.5%) were MRD+ after blinatumomab. Two‐year OS in this group was 61%. Twenty pts (34%) received allo‐HSCT. In R\R ALL pts CR MRD− was achieved in 30 pts (48%), 9 pts (14%) were MRD+ after blinatumomab, 24 pts (38%) had no hematological response. Two‐year OS in R/R ALL was 43%. Fifteen pts (24%) received allo‐HSCT. OS in CR MRD− patients who received allo‐HSCT was not significantly different in comparison with patients who received blinatumomab as a monotherapy (84% vs 71%, p = 0.08). No significant differences in DFS were observed at two years in CR MRD− pts depending status of the disease before therapy‐ MRD vs R/R (66% vs 59%, p = 0.81).Of the reported adverse events, febrile fever was the most common 91pts (76%), the other complications were neutropenia 43 (35%), thrombocytopenia 46 (38%), infection 32 (26%), neurotoxicity 29 (24%), cytokine‐release syndrome 8 (7%). All complications were reversible.Summary/Conclusion:Blinatumomab is effective option in patients with high risk B‐ALL especially in the group with MRD persistence after previous chemotherapy and facilitates effective bridging to HSCT. Blinatumomab therapy is generally well tolerated.