Abstract
Simple SummaryImmunotherapies are modern treatment modalities, giving hope for improvements of frozen cure rates in many childhood malignancies. More intensive cytotoxic chemotherapy cycles didn’t improve cure rates, only increase number of adverse events. Blinatumomab, a bispecific CD3/CD19 antibody construct, has been successfully used in relapsed/refractory r/r B-cell precursor ALL (BCP-ALL) as a bridge to hematopoietic stem cell transplantation (HSCT). We retrospectively assessed the efficacy and toxicity of blinatumomab in 13 children with r/r BCP-ALL. The response rate in our cohort of patients was 85%, with subsequent feasible HSCT in 11 out of 13 children. Although our study had some limitations with regard to its retrospective design and limited patient population, it clearly showed blinatumomab as not only a feasible but also an effective therapeutic option in pretreated children with r/r BCP-ALL, with a tolerable toxicity profile, paving the way for an HSCT procedure. To date, this is the first retrospective study from Poland on efficacy and toxicity of blinatumomab therapy in children with r/r ALL.Despite the progress that has been made in recent decades in the treatment of pediatric acute leukemias, e.g., converting acute lymphoblastic leukemia (ALL) from a fatal to a highly curable disease, 15–20% of children still relapse. Blinatumomab, a bispecific CD3/CD19 antibody construct, has been successfully used in relapsed/refractory r/r B-cell precursor ALL (BCP-ALL) as a bridge to hematopoietic stem cell transplantation (HSCT). We retrospectively assessed the efficacy and toxicity of blinatumomab in 13 children with r/r BCP-ALL. Between 2017 and 2021, thirteen children, aged 1–18 years, with r/r BCP-ALL were treated with blinatumomab. Two patients were administered blinatumomab for refractory relapse without complete remission (CR), one due to primary refractory disease, and ten patients were in CR with minimal residual disease (MRD) ≥ 10−3. The response rate in our cohort of patients was 85%, with subsequent feasible HSCT in 11 out of 13 children. Ten children reached MRD negativity after the first blinatumomab administration. The three-year OS for the study patients was 85% (Mantel–Cox, p < 0.001) and median follow-up was 24.5 (range: 1–47). All responders proceeded to HSCT and are alive in CR, and MRD negative. Although our study had some limitations with regard to its retrospective design and limited patient population, it clearly showed blinatumomab as not only a feasible but also an effective therapeutic option in pretreated children with r/r BCP-ALL, with a tolerable toxicity profile, paving the way for an HSCT procedure.
Highlights
Acute lymphoblastic leukemia (ALL) is one of the most common pediatric malignancies, childhood cancers are rare [1]
We present data on children with r/r B-cell precursor ALL (BCP-ALL) treated with blinatumomab in a compassionate, off-label setting as an effective bridging therapy to hematopoietic stem cell transplantation (HSCT)
Children with r/r BCP-ALL presenting CD19 expression on leukemic cells were eligible for the assessment
Summary
Acute lymphoblastic leukemia (ALL) is one of the most common pediatric malignancies, childhood cancers are rare [1]. Despite the currently high complete remission rate (more than 95% newly diagnosed ALL patients) using risk-adapted protocols, approximately 15–20% of children will eventually relapse, with 8–10% dying from disease progression or treatment-related complications [2,3]. Survival rates after relapse significantly depend on leukemic blast immunophenotype (B-ALL vs T-ALL) and time of relapse. The cure rates range from less than 30% for early relapses to 50−60% for late relapses [4]. Current standard-of-care therapies for relapsed/refractory ALL (r/r ALL), based on cytotoxic chemotherapeutic agents, are associated with severe acute and long-term toxicities, and quite often cause treatment-related death. New treatment modalities of reduced toxicity are an attractive option for heavily pretreated children and provide an opportunity to improve outcomes in those with r/r ALL
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