Blinatumomab in Children and Adolescents with Relapsed/Refractory B Cell Precursor Acute Lymphoblastic Leukemia: A Real-Life Multicenter Retrospective Study in Seven AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) Centers.

Giuliana Beneduce,Carmelo Rizzari,Simone Cesaro,Maria C Putti,Anna M Testi,Giuseppe Menna,Monica Cellini,Nicoletta Bertorello,Elena Barisone,Rosanna Parasole,Fara Petruzziello,Pio Stellato,Antonia De Matteo,Antonella Colombini

doi:10.3390/cancers14020426

Abstract

Simple SummaryBlinatumomab, a bispecific T-cell engager, binding T-cell CD3 and B-cell CD19 antigens, has remarkably enlarged the treatment options for patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL). The aim of our study was to retrospectively assess the safety and efficacy profile of blinatumomab in 39 r/r ALL children treated in seven AIEOP centers in a compassionate or off-label program. This report is among the largest multicentric real-life retrospective analyses on blinatumomab in pediatric r/r BCP ALL. Blinatumomab showed a tolerable safety profile (34.8% of adverse events ≥grade 3, no cytokine release syndrome and no associated toxic deaths) and proved to be very effective (complete remission rate 46% in the 13 patients with ≥5% blasts and 81% PCR/FC MRD negativity in the 26 patients with <5% blasts) in this group of patients affected by r/r BCP-ALL already treated in the frame of very intensive front-line and relapsed protocols.Five-year event-free survival in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) currently exceeds 80–85%. However, 15–20% of patients still experience a relapsed/refractory disease. From 1 January 2015 to 31 December 2020, thirty-nine patients, 0–21 years old with r/r BCP-ALL were treated with blinatumomab with the aim of inducing remission (n = 13) or reducing MRD levels (n = 26) in the frame of different multiagent chemotherapy schedules, in seven AIEOP centers. Patients were treated in compassionate and/or off-label settings and were not enrolled in any controlled clinical trials. Treatment was well tolerated; 22 (56.4%) patients reported adverse events (AE) on a total of 46 events registered, of which 27 (58.7%) were ≤2 grade according to CTCAE. Neurological AEs were 18 (39.1%); only two patients required transient blinatumomab discontinuation. Complete remission (CR) rate was 46% for the 13 patients treated with ≥5% blasts and 81% PCR/FC MRD negativity in the 26 patients with blasts < 5%. Median relapse-free survival was 33.4 months (95% CI; 7.5–59.3); median overall survival was not reached over a mean follow-up of 16 months. In our study, as in other real-life experiences, blinatumomab proved to be effective and well-tolerated, able to induce a high rate of CR and MRD negativity.

Highlights

Current risk-adapted protocols for children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) achieve 5-year overall survival (OS) rates exceeding 90% [1,2].15–20% of patients still experience a relapsed/refractory disease with 5-yearOS in first relapse of about 50% [3,4,5]
The main goals of this study were to evaluate the toxicity as incidence of treatmentrelated adverse events (AEs) and the efficacy pattern as: (i) morphologic complete remission (CR) rate, defined as
The disease was in first relapse in 23 (59%) and in second or later relapse in 12 patients (31%)

Summary

Introduction

Current risk-adapted protocols for children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) achieve 5-year overall survival (OS) rates exceeding 90% [1,2].15–20% of patients still experience a relapsed/refractory disease with 5-yearOS in first relapse of about 50% [3,4,5]. Current risk-adapted protocols for children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) achieve 5-year overall survival (OS) rates exceeding 90% [1,2]. 15–20% of patients still experience a relapsed/refractory disease with 5-year. Primary refractory disease and second or greater relapse have a dismal prognosis even with intensive chemotherapy treatment and allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Antigen-targeted therapy approaches have significantly improved the prognosis of pediatric relapsed/refractory. Blinatumomab is a bispecific T-cell engager (BiTE) with two different single-chain Fv fragments binding T-cell CD3 and B-cell CD19 antigens [9]. It has been fully approved since July 2017 by the Food and Drug Administration (FDA) and European Medicines

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