Poster Session II: Acute lymphoblastic leukemia - Clinical
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.
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.
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.
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.
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.