Acute lymphocytic leukaemia (ALL) is a rare blood cancer with an incidence of just over 5,500 patients in the US, both paediatric and adult. ALL is classified as either B-ALL (more common) and T-ALL, with T-ALL having a far more dismal prognosis. Decades of intensive chemotherapy research have yielded substantial cure rates with intensive chemotherapy regimens in paediatric patients, and a lower cure rate but improved five-year survival rates in adult patients.
For relapsed/refractory (R/R) patients, the prognosis is universally poor, and even poorer in the rarer T-ALL subset. Chemotherapy regimens vary wildly depending on the country and institution, but in younger patients, they involve a combination of asparaginase products + chemotherapy, whereas in older patients it is typically chemotherapy only, such as the well-established hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) regimen. Upon relapse, one of the most common options for B-ALL patients is Amgen’s bispecific CD19/CD3 T-cell engager Blincyto (blinatumomab), which received FDA approval for R/R patients in 2014. Blincyto received a label expansion from the FDA in 2018 for use in patients with minimal residual disease (MRD)-positive status after intensive chemotherapy in the first line.
At the 64th American Society of Haematology (ASH) Annual Meeting and Exposition on 10–13 December, new data were presented from the randomised Phase III ECOG-ACRIN E1910 study of Blincyto in the first line for MRD-negative patients (abstract #LBA-1). Patients had to be negative for the BCR-ABL1 translocation and were aged between 30 and 70 years. Patients (n=224) were taken to MRD-negative status with a BFM-like, adapted chemotherapy regimen that could also include asparaginase and rituximab (chemo) depending on patient characteristics, and were then randomised to receive either chemo-based consolidation or chemo + Blincyto-based consolidation, n=112 in each arm.
Patients that did not achieve remission (19%) were taken off the study protocol. The primary endpoint was overall survival (OS), and stem cell transplant was allowed for both arms at investigators’ discretion; 22 patients in each arm received an allogeneic transplant. At a median follow-up of 43 months, the median OS was not reached for the Blincyto arm versus 71.4 months for the chemotherapy arm (hazard ratio [HR]: 0.42). No new safety signals were reported.
A large improvement in OS for newly-diagnosed adult B-ALL patients has not been demonstrated in years. As such, this trial makes a combination of a chemotherapy regimen + Blincyto the new standard of care for newly diagnosed B-ALL BRC-ABL1-negative patients of ages 30 to 70 years who achieve a complete remission regardless of MRD status. Since the trial was led by the National Cancer Institute, it is very likely that the data will allow for a supplemental biologics license application by Amgen for a label expansion.
The economic implications of this new regimen will be substantial – even two cycles of Blincyto will at a minimum double the cost of the consolidation regimen. GlobalData estimates the US cost per Blincyto cycle to be around $66,000, which based on the proposed regimen could add an additional $130,000–250,000 for each patient treated in the US. This could add more than $100m in annual US sales for Blincyto, whose US sales reached $278m last year.