Outcomes for Australian children with relapsed/refractory acute lymphoblastic leukaemia treated with blinatumomab

Abstract

We report on the Australian experience of blinatumomab for treatment of 24 children with relapsed/refractory precursor B‐cell acute lymphoblastic leukaemia (B‐ALL) and high‐risk genetics, resulting in a minimal residual disease (MRD) response rate of 58%, 2‐year progression‐free survival (PFS) of 39% and 2‐year overall survival of 63%. In total, 83% (n = 20/24) proceeded to haematopoietic stem cell transplant, directly after blinatumomab (n = 12) or following additional salvage therapy (n = 8). Four patients successfully received CD19‐directed chimeric antigen receptor T‐cell therapy despite prior blinatumomab exposure. Inferior 2‐year PFS was associated with MRD positivity (20%, n = 15) and in KMT2A‐rearranged infants (15%, n = 9). Our findings highlight that not all children with relapsed/refractory B‐ALL respond to blinatumomab and factors such as blast genotype may affect prognosis.

Blinatumomab in Pediatric Acute Lymphoblastic Leukemia—From Salvage to First Line Therapy (A Systematic Review)

“…All children received HSCT, and the 12-month EFS compares favorably with historical outcomes [32]. In contrast, in an Australian study, infants with KMT2A-rearranged leukemia had poor outcomes with an MRD response rate of only 44% [37]. This disparity might be explained by pretreatment or tumor burden differences prior to treatment.…”

“…The results of the phase I/II study and several single-institution or national retrospective evaluations show that children with R/R-ALL show a response to blinatumomab ranging from 34-38% [21,36] to around 60% [25,37]. In almost all studies published to date, there is evidence or at least a trend of improved survival if blinatumomab is administered prior to or after allogeneic HSCT [22,25,26,32,36].…”

“…Continuous concomitant medication with imatinib or dasatinib leads to an important increase in adverse events, necessitating alternative therapeutic options. Sutton and colleagues observed relatively good outcomes for patients with Philadelphia-positive or Philadelphia-like ALL treated with blinatumomab [37]. Unfortunately, most upfront trials with blinatumomab for children open today do not include patients with Ph+ ALL, with the exception of Total Therapy XVII (NCT03117751).…”

“…All survivors underwent haploidentical hematopoietic stem cell transplantation after treatment with blinatumomab. Sutton and colleagues very recently published the Australian experience with blinatumomab in children with R/R-ALL and high-risk genetics [37]. Overall, MRD response was 58%, median follow up was 26 months (14-42 months), 83% proceeded to HSCT and inferior progression-free survival (PFS) was associated with MRD positivity and KMT2A-rearranged leukemia.…”

“…The Australian group described two patients with CD19-negative relapses, one of which also harbored a KMT2A rearrangement and showed myeloid differentiation; however, the leukemias of most patients who relapsed remained CD19 positive [37].…”