BLINATUMOMAB - BASED THERAPIES IN CHILDREN AND ADULTS WITH MRD+ AND R/R B-ALL, EXPERIENCE FROM A SINGLE CENTER (CIC 725)
Author(s): ,
Inna Markova
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Sergey Bondarenko
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Olesya Paina
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Polina Kozhokar'
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Anastasia Frolova
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Ildar Barkhatov
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Elena Babenko
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Alexander Alyanskii
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Kirill Ekushov,
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Tatyana Gindina
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Elena Darskay
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Bella Aubova
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Elena Semenova
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Ivan Moiseev
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
,
Ludmila Zubarovskaya
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
Boris Afanasyev
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University,St. Petersburg,Russian Federation
EHA Library. Markova I. Jun 15, 2019; 267261; PS960
Inna Markova
Inna Markova
Contributions
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Abstract

Abstract: PS960

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

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.

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.  

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): Monoclonal antibody, Relapsed acute lymphoblastic leukemia

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