Immunotherapy with Blinatumomab Prolongs Survival in Acute Lymphoblastic Leukemia
Treatment with CD19-targeted immunotherapy blinatumomab (Blincyto) as a single agent showed antileukemic activity in patients with minimal residual disease (MRD) Philadelphia chromosome (Ph)-positive B-cell precursor acute lymphoblastic leukemia (ALL) whose disease progressed after or was intolerant to a second-generation or later tyrosine kinase inhibitor (TKI). The results were presented at ASH 2015.
“This is a proof-of-principle study with a new compound in an MRD-positive population with an MRD-based end point,” said Giovanni Martinelli, MD, Associate Professor, Institute of Haematology, S. Orsola-Malpighi University Hospital, Bologna, Italy. “This is a new indication to use a drug preemptively before patients experience a full relapse.”
Blinatumomab is a bispecific T-cell engaging antibody construct that has shown antileukemic activity in adults with relapsed or refractory Ph-negative ALL.
“Blinatumomab induced a high complete MRD response rate of 80%, and 67% of patients were able to receive stem-cell transplant in continuous remission after blinatumomab,” Dr Martinelli added.
The prognosis of patients with relapsed or refractory Ph-positive ALL is dismal despite the introduction of TKIs, which may be used as single agents or in combination regimens.
Of the 45 patients treated with blinatumomab, 44 were resistant to second-generation or later TKIs.
“The overall survival of the study was analyzed over the median follow-up of 30 months, so these are really mature data,” said Dr Martinelli. “The median overall survival of 36 months is a very favorable result, keeping in mind that in relapsed ALL, median survival is around 6 months.”
At 18 months, the median relapse-free survival was also high, Dr Martinelli noted.
“Blinatumomab may have contributed to prolonged relapse-free survival and overall survival in patients with MRD-positive ALL,” said Dr Martinelli. “MRD response was associated with improved overall survival, relapse-free survival, and remission duration.”
In addition, patients treated in first remission had improved relapse-free survival and remission duration compared with patients who were treated in subsequent remission.
Among patients who experienced neurologic events during the study, the majority had a grade ≤2 adverse effect.
“Twelve patients interrupted or discontinued treatment due to grade 3 or greater neurologic events,” Dr Martinelli observed, “but this will be further improved as physicians gain experience with this very new treatment.”
“Overall, I think this is a very-efficient compound to treat MRD-positive ALL,” Dr Martinelli concluded. “I think these are very promising results.”