PS960 BLINATUMOMAB ‐ BASED THERAPIES IN CHILDREN AND ADULTS WITH MRD+ AND R/R B‐ALL, EXPERIENCE FROM A SINGLE CENTER (CIC 725)

• Published in: HemaSphere 2019-06, Vol.3 (S1), p.432-n/a
• Main Authors: Markova, I., Bondarenko, S., Paina, O., Kozhokar’, P., Frolova, A., Barkhatov, I., Babenko, E., Alyanskii, A., Ekushov, K., Gindina, T., Darskay, E., Aubova, B., Semenova, E., Moiseev, I., Zubarovskaya, L., Afanasyev, B.
• Format: Article
• Language: English
• ISSN: 2572-9241; 2572-9241
• DOI: 10.1097/01.HS9.0000562144.62037.a3

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 fe