Blood cancers

Aussie kids with relapsed/refractory ALL show 58% overall MRD response to blinatumomab

Genetic features may be the best indicator of responsiveness to blinatumomab, according to Australian clinicians who report which children with relapsed-refractory paediatric ALL respond to the bi-specific T-cell engager (BiTE) in the real-world setting.

Their review of 24 cases outside clinical trials found 38% of patients were MRD-negative after blinatumomab – indicating a complete MRD response – and had fewer relapses and better 2-year PFS than the MRD-positive patients (75% vs. 20%, p = .0099).

Together with the partial responders, the overall MRD response was 58%.

Most patients (83%) proceeded to HSCT directly after blinatumomab or after MRD had been reduced with salvage therapies.

The four children who did not receive HSCT had early deaths.

“Previous studies of children with high-risk B-ALL highlight the success of reducing MRD with blinatumomab alone prior to HSCT,” the study authors said.

“In our study of high-risk relapsed/refractory paediatric B-ALL, blinatumomab was used as a bridge to HSCT in half, and subsequent salvage was feasible in another third using inotuzumab, dasatinib, chimeric antigen receptor (CAR) T-cell therapy or intensive myeloid-directed chemotherapy.”

The study, published in Paediatric Blood & Cancer, found relatively good outcomes in patients with Philadelphia chromosome-positive or Philadelphia chromosome-like ALL, with 2-year PFS of 70%.

On the other hand, KMT2A-rearranged ALL were associated with poor outcomes, with a complete/partial MRD response rate of 44%, 2-year PFS of 15% and 2-year OS of 37%.

“These findings provide rationale to assess if children within genetically defined subsets would gain greater benefit from blinatumomab in the upfront setting,” they said.

Two international trials, reported recently in the limbic, have shown blinatumomab more effective and less toxic than chemotherapy for first relapse of paediatric B-ALL.

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