Real-World Multicenter Experience in Tumor Debulking Prior to Blinatumomab Administration in Adult Patients With Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia.

Massimiliano Bonifacio,Robin Foà,Sabina Chiaretti,Cristina Papayannidis,Nicola Fracchiolla,Simona Sica,Giovanni Pizzolo,Mario Annunziata,Mario Delia,Federico Lussana

doi:10.3389/fonc.2021.804714

Abstract

Blinatumomab is an immunotherapeutic agent with dual specificity for CD3 and CD19 that is approved for the treatment of relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL). A steroid based pre-treatment is recommended before administering blinatumomab to patients with a high tumor burden to minimize the risk of tumor lysis syndrome, but the optimal debulking regimen and whether it can improve responses remain unclear. The present study retrospectively evaluated real-world outcomes following tumor debulking and blinatumomab infusion in R/R B-ALL adult patients treated at 7 Italian centers. Data were collected from 34 patients. The choice of the cytoreductive therapy was made by the treating clinician on an individual patient basis; regimens included chemotherapy (n=23), steroids (n=7) and tyrosine kinase inhibitors alone or in combination (n=4). The rate of complete responses (CR) and complete minimal residual disease (MRD) responses in CR patients were 67.6% and 81% respectively, after 2 cycles of blinatumomab. Moreover, among patients with a high tumor burden 50% obtained a CR, with 89% of them also achieving a complete MRD response. Favorable responses were also obtained in patients over 50 years of age at treatment initiation. Overall, 7 of 23 patients in CR after blinatumomab underwent hematopoietic stem cell transplantation. The results of this retrospective study highlight the heterogeneity in the use of pre-blinatumomab tumor debulking in real-life clinical practice. Nonetheless, debulking pre-treatment enhanced responses to blinatumomab compared to historic studies, indicating that this strategy may help to improve outcomes for R/R B-ALL patients.

Highlights

B-cell precursor (BCP) acute lymphoblastic leukemia (B-ALL) accounts for almost 75% of all cases of adult ALL [1]
The purpose of the present study was to evaluate the response to blinatumomab following prior debulking therapy in R/R B-ALL adult patients treated in the clinical practice in Italy
All patients enrolled in those studies at the participating centers were screened and all patients who performed a debulking treatment prior to blinatumomab administration were selected for the present study

Summary

Introduction

B-cell precursor (BCP) acute lymphoblastic leukemia (B-ALL) accounts for almost 75% of all cases of adult ALL [1]. Relapsed or refractory B-ALL (R/R B-ALL) is associated with poor event-free survival (EFS), overall survival (OS) and a cure rate of less than 10% [4,5,6], and its treatment remains a clinical challenge [3]. This is attributable to the persistence of chemoresistant minimal residual disease (MRD) following initial chemotherapy, which increases the risk of hematologic relapse and is regarded as the most important prognostic factor in ALL [5, 7,8,9]. Blinatumomab was first approved by the Food and Drug Administration (FDA) for the treatment of R/R B-ALL and later for B-ALL patients with MRD [10]

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