Blinatumomab Has ‘Notable’ Activity Against Adult ALL

A phase II trial reports on the response to targeted immunotherapy with blinatumomab in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia

medwireNews: Blinatumomab, a T-cell Antibody construct that targets CD19 and CD3, has activity in adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia (ALL), shows a study published in The Lancet Oncology.

Max Topp, from Universitatsklinikum Wurzburg in Germany, and colleagues comment that the results of their prospective phase II trial, the largest so far for this agent, suggest an important future therapeutic role for blinatumomab in this patient population.

Their multicentre study included 189 adults with relapsed or refractory disease who were specifically selected because they had a poor prognosis. The participants received up to five cycles of open-label, intravenous blinatumomab at a dose of 9 µg/day for the first week and 28 µg/day for the next 3 weeks, followed by a 2-week break from treatment. Patients with a high tumour burden were given dexamethasone before blinatumomab.

Sixty-three (33%) patients achieved complete remission and 18 (10%) had a complete response with partial haematological recovery of peripheral blood counts (CRh) in the initial two cycles of treatment. Of these 81 responders, 64 (79%) achieved complete response or CRh in the first cycle.

After a median follow-up of 8.9 months, median relapse-free survival for patients who achieved complete response and CRh was 6.9 months and 5.0 months, respectively. And median overall survival for the entire study cohort was 6.1 months.

The team explains that the goal for ALL patients is to achieve remission followed by allogeneic haematopoietic stem-cell transplantation (HSCT), and this was achieved by 32 (40%) of the study participants who responded to treatment. The majority of responders who did not proceed to allogeneic HSCT had either already received stem-cell transplantation or were aged 65 years or older.
Febrile neutropenia, neutropenia and anaemia were the most common grade 3 or 4 adverse events, occurring in respectively 25%, 16% and 14% of blinatumomab-treated patients. Thirteen percent of patients had grade 3 or 4 neurological toxicities, the majority of which resolved.

Only three participants developed grade 3 cytokine release syndrome following treatment and there were no grade 4 or 5 events. The authors attribute this low frequency to the dexamethasone pretreatment and the dose-step regimen.

Of the 23 patient deaths during the trial, most of which were related to infection, three fatal cases of infection were thought possibly related to blinatumomab treatment.

“The data suggest that blinatumomab could provide a new therapeutic approach in relapsed or refractory acute lymphoblastic leukaemia”, say the researchers.

They conclude: “Further assessment of blinatumomab treatment earlier in the course of the disease and in combination with other treatment approaches is warranted.”

Reference

Topp MS, Gökbuget N, Stein AS, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 2014; Published online 15 December. doi: 10.1016/S1470-2045(14)71170-2

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