Amgen announced that new data from three phase 2 trials support the efficacy and safety of Blincyto (blinatumomab) in adults with acute lymphoblastic leukemia (ALL). These data were presented in oral sessions at the 57th Annual Meeting and Exposition of the American Society of Hematology (ASH) in Orlando, Florida.

In a phase 2 confirmatory multicenter single-arm trial (BLAST), adult patients with B-cell precursor ALL with minimal residual disease (MRD) who received Blincyto monotherapy demonstrated clinically meaningful relapse-free survival (RFS), as measured in the key secondary endpoint. Median RFS was 18.9 months following initiation of Blincyto. MRD refers to the presence of leukemia blast cells below the limits of detection available with standard assessment. Results from the phase 2 BLAST trial were nominated for inclusion in the Best of ASH Session on December 8.

Other presentations demonstrate Blincyto's potential in a high risk subpopulation of patients with relapsed or refractory Philadelphia chromosome-positive (Ph+) B-precursor ALL and confirm Blincyto's efficacy in a subset of patients with relapsed or refractory Philadelphia chromosome-negative (Ph-) ALL after an allogeneic hematopoietic stem cell transplantation (alloHSCT), who typically have poor outcomes with current therapies.

"A key goal in the treatment of blood cancers is to prevent relapse from occurring," said Sean E. Harper, M.D., executive vice president of research and development at Amgen.

"Achieving a complete minimal residual disease, or MRD response, is important because having no detectable MRD places ALL patients at a lower risk for relapse when compared to patients with persistent or recurrent MRD. The data presented are highly encouraging because they support the potential of Blincyto in a broader spectrum of ALL patients, including those at an earlier stage of disease."

ALL is a rare and rapidly progressing cancer of the blood and bone marrow. In adult patients with relapsed or refractory ALL, median overall survival (OS) is just three to five months. Currently, there is no broadly accepted standard treatment regimen for adult patients with relapsed or refractory ALL beyond chemotherapy. Around 15-30 per cent of adult ALL patients are Ph+ and these patients typically have a poor response to standard therapy, short remission duration and low survival rates.

In this long-term follow up from the phase 2 '203 study of 116 patients with B-precursor ALL and persistent or recurrent MRD after first-line chemotherapy, patients who achieved an MRD complete response with Blincyto had a longer OS, RFS and duration of remission (DOR) compared with those not achieving an MRD complete response, with a median OS in MRD-negative patients of 40.4 months. In data reported at ASH 2014, treatment with Blincyto resulted in complete MRD response in cycle 1 in 78 per cent of patients.

The most clinically relevant adverse events (AEs) were neurologic events, including tremor (30 per cent), aphasia (13 per cent), dizziness (8 per cent), ataxia and paresthesia (6 per cent each), and encephalopathy (5 per cent). Rates decreased over time (cycles 1, 2, 3 and 4) for any neurologic event (47 per cent, 24 per cent, 15 per cent and 15 per cent) and any grade 3 or higher neurologic event (10 per cent, 4 per cent, 0 per cent and 0 per cent).

In the phase 2 ALCANTARA study, Blincyto showed antileukemic activity in very poor prognosis patients with relapsed or refractory Ph+ B-precursor ALL after failure of at least one second-generation tyrosine kinase inhibitor (TKI) therapy, with 36 per cent of patients achieving complete remission or complete remission with partial hematological recovery (CR/CRh) during the first two treatment cycles. Of patients who achieved CR/CRh, 88 per cent achieved a complete MRD response. Equivalent response rates were observed in patients with kinase-domain mutations in BCR-ABL such as T315I (four achieved CR/CRh; all four also achieved a complete MRD response).

Patient incidence of grade 3 or higher treatment-emergent AEs was 82 per cent, most commonly febrile neutropenia (27 per cent), thrombocytopenia (22 per cent), anemia (16 per cent), pyrexia (11 percent) and neurologic events (7 per cent). There were no episodes of grade 3 or higher cytokine release syndrome.

In this analysis from the pivotal phase 2 '211 trial, Blincyto induced a CR/CRh rate of 45 per cent in a subset of 64 heavily pretreated patients with Ph- ALL who had relapsed or were refractory after an alloHSCT.

In total, 88 per cent of patients had grade 3 or higher treatment-emergent AEs, with the most frequent including neutropenia (22 per cent), febrile neutropenia (20 per cent), anemia (17 per cent) and thrombocytopenia (14 per cent). Six patients reported treatment-emergent graft vs. host disease (GvHD), two of which were grade 3 or higher.

Blincyto is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. Blincyto was granted breakthrough therapy and priority review designations by the US Food and Drug Administration, and is now approved in the US for the treatment of Ph- relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

BiTE antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body's immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers.