Three phase 2 studies presented at the annual meeting of the American Society of Hematology support the potential for blinatumomab in a broader group of patients with acute lymphocytic leukemia.
The studies, presented December 5th-8th 2015 in Orlando, FL, provide data for blinatumomab in adults with B-cell precursor acute lymphocytic leukaemia (ALL) and minimal residual disease (MRD), high-risk populations with relapsed or refractory Philadelphia chromosome-positive (Ph+) B precursor ALL, and patients with relapsed or refractory Philadelphia chromosome negative (Ph-) B precursor ALL after allogeneic hematopoietic stem cell transplantation (alloHSCT).
For adult patients with relapsed or refractory ALL, median overall survival is just 3-5 months, and there is no broadly accepted standard treatment regimen for those with relapsed or refractory ALL beyond chemotherapy.
Blinatumomab is a first-in-class bispecific T-cell engager (or BiTE) that was approved by the Food and Drug Administration (FDA) in December 2014 for patients with relapsed or refractory Philadelphia chromosome-negative (Ph-) ALL of B-cell lineage.
The BiTE antibody technology acts as a bridge linking two amino acid sequences, one binding to T cells via the CD3 receptor, and the other to tumor cells via a tumor-specific molecule.
In abstract 680, Nicola Gökbuget, from Goethe University in Frankfurt, Germany, and colleagues evaluated long-term outcomes in 116 patients with B-cell precursor ALL and MRD >10 -3 after > 3 intensive chemotherapy treatments.
Subjects were given blinatumomab 15µg/m2/day by continuous IV infusion for 4 weeks, followed by a 2-week break (one cycle). MRD responders in cycle one received up to three additional cycles or underwent hematopoietic stem cell transplants.
Results show that 80% of patients achieved a complete MRD response, with 67% able to remain in continuous remission until transplant. Overall survival was 36.5 months.
Furthermore, overall survival was significantly more likely among those who achieved a complete MRD response (P=0.002), and duration of complete remission was longer for these patients (P=0.004). Also, patients in their first remission at baseline had longer relapse-free survival (P=0.004). Relapse-free survival after a median follow-up of 29.9 months was 54%.
The most clinically relevant adverse events were neurologic events, including tremor (30%), aphasia (13%), dizziness (8%), ataxia and paraesthesia (6%) and encephalopathy (5%).
“Blinatumomab may contribute to prolonged relapse-free survival and overall survival in patients with MRD-positive ALL,” concluded Gökbuget.
In the ALCANTARA trial (abstract 679), 45 patients with adult Ph+ B-cell precursor ALL, who had relapsed after or were refractory to at least one second generation TKI, received blinatumomab by continuous intravenous infusion (4 weeks on, 2 weeks off) for up to five cycles. The Ph+ ALL population is known to have a historically poor prognosis.
Results, presented by Giovanni Martinelli from the Institute of Haematology and Medical Oncology in Bologna, Italy, showed that 36% of patients achieved complete response – complete remission with partial hematological (CR/CRh) recovery.
Furthermore, 88% of patients achieved complete MRD responses. Four of the 16 patients with blinatumomab-induced remission went on to HSCT, one of whom died 100 days post-transplant.
The median overall survival was 7.1 months, and relapse-free survival was 6.7 months among responders. Adverse events led to discontinuations in 7% of patients, with febrile neutropenia (27%) and thrombocytopenia (22%) being most common.
In abstract 861, Anthony Stein, from Gehr Leukemia Center in Duarte, CA, and colleagues gave 64 patients whose Ph- ALL had relapsed after prior allogeneic hematopoietic stem cell transplants blinatumomab. Patients received blinatumomab by continuous intravenous infusion (4 weeks on, 2 weeks off) for up to five cycles.
Results showed that the primary endpoint complete remission or complete remission with partial haematologic recovery (CR/CRh) was reported in 45% (29/64, 95% CI 33-58) of patients with 76% (22) of these achieving CR/CRh in the first cycle. Blast-free hypoplastic/aplastic bone marrow was found in 6% of patients, and 19% did not respond to therapy.
Among the 18 patients who achieved complete responses in the first two cycles of blinatumomab, 16 (89%) had MRD responses, and 15 (83%) had complete MRD responses. Overall, 88% (56) of patients had grade >3 treatment emergent adverse events, with the most frequent including neutropenia (22%), febrile neutropenia (20%), anemia (17%) and thrombocytopenia (14%).
For future investigations to prolong remission in this poor outcome patient group, Stein suggested, the addition of other immunotherapies to the treatment regimen should be considered.