Insights from the Greek experience of the use of Blinatumomab in pediatric relapsed and refractory acute lymphoblastic leukemia patients

 Maria Ampatzidou, Antonis Kattamis, Margarita Baka, Georgios Paterakis, Theodora Anastasiou, Marianna Tzanoudaki, Aikaterini Kaisari, Georgia Avgerinou, Dimitrios Doganis, Vassilios Papadakis, Vassiliki Kitra, Sophia Polychronopoulou

Abstract:

Pediatric refractory or relapsed acute lymphoblastic leukemia (ALL) poses unique therapeutic challenges, with novel immunotherapy approaches offering potential cure opportunities. In this frame, the use of Blinatumomab may induce durable remissions, serving as a successful bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Herein, we retrospectively summarize the Greek experience on pediatric relapsed/refractory B-cell precursor ALL patients that were treated with Blinatumomab in a compassionate, off-label setting as an effort to achieve disease clearance and proceed to allo-HSCT. In our cohort of 9 patients, 6/9 (66.7%) responded to Blinatumomab, achieving complete morphological remission (CR) after the 1st cycle, while minimal/measurable residual disease (MRD)-negativity (<10–4) after the 1st cycle was achieved in 2/2 patients (100.0%) with prior CR. A successful bridge to HSCT was feasible in 5/9 patients (55.6%). Median relapse-free survival (RFS) was 3.0 months (range 0.5-21.4 months) and median overall survival (OS) was 8.7 months (range 1.4-47.1 months) for the whole pediatric cohort. There was a trend of prolonged survival among patients who achieved MRD response after the 1st Blinatumomab administration. MRD response (defined as the >=2-log reduction of MRD value before and after Blinatumomab administration), was associated with a median RFS/OS of 7.4/7.6 months, while lack of MRD response was associated with a median RFS/OS of 0.5/3.0 months, respectively. Novel therapeutic maneuvers, in order to overcome disease resistance, i.e. increased usage of Blinatumomab dose (45 μg/m2/day), combination with donor lymphocyte infusions (DLIs), use of other immunotherapy salvage approaches (inotuzumabozogamicin), are herein discussed. Additionally, the optimal number of Blinatumomab cycles, the CD19-negative relapses and lineage switch, are also addressed. Our data although referred to a limited, however refractory or relapsed and heavily pretreated number of patients, strongly suggest that Blinatumomab may well induce sustained remissions and serve as an effective bridge to HSCT. Whether immunotherapy combined with chemotherapy can outweigh the need for subsequent allo-HSCT, if incorporated into frontline high-risk ALL therapy, remains an optimistic issue to be verified in future randomized clinical trials.