In a nutshell
The study evaluated outcomes of combining ofatumumab (Arzerra) with hyper-CVAD chemotherapy in patients with Philadelphia chromosome (Ph)-negative CD20-positive B-cell acute lymphoblastic leukemia (B-ALL). The authors found that the combination was safe and effective in such patients.
Philadelphia chromosome (Ph) is a cancerous genetic abnormality. It is lacking in patients with Ph-negative B-ALL. B-cells are specialized white blood cells and they become cancerous in B-ALL. CD20 is a protein on B-cells’ surface. Ofatumumab can kill leukemic B-cells by targeting CD20. Hyper-CVAD is a chemotherapy combination of hyperfractionated cyclophosphamide (Cytoxan), vincristine (Oncovin), doxorubicin (Adriamycin), and dexamethasone (Decadron). Hyper-CVAD is used in small frequent doses to treat ALL. Ofatumumab alone is effective against chronic lymphocytic leukemia. However, its use in combination with hyper-CVAD in CD20-positive B-ALL has not been explored.
Methods & findings
The study included 69 Ph-negative CD20-positive patients with B-ALL. 67 had newly diagnosed B-ALL. 2 patients had B-cell lymphoblastic lymphoma (B-LL). Patients were treated with 8 courses of hyper-CVAD and 8 doses of ofatumumab as frontline or initial therapy. 65 patients were previously untreated. 4 were in complete remission (CR) after one course. CR means the absence of all cancer symptoms. The average follow-up period was 44 months.
After an average follow-up of 44 months, 67% of patients survived. 54% of patients survived with CR. 30% of patients relapsed. Event-free survival (EFS) defined how long patients survive without relapse, failing to respond to therapy or death. THE average EFS was 51 months. EFS at 4-years was estimated to be 59%. Overall survival (OS) at 4-years was estimated to be 68%. 4-year EFS was estimated as 69% for adolescents and young adults (AYA) and 51% for patients aged 40 years and older. 4-year OS was 74% for AYA and 63% for 40 years and older.
Out of 65 previously untreated patients, 64 (98%) achieved remission after 2 courses of treatment. The treatment was well tolerated with mild to moderate side-effects. The most common side effects were low protein and calcium levels and infusion reactions. The most common serious reactions were infections. No death occurred due to ofatumumab therapy.
The bottom line
The study concluded that combining ofatumumab with hyper-CVAD is safe and effective as a frontline therapy in patients with Ph-negative CD20-positive B-ALL.
The fine print
This study was a phase-2 clinical trial and funded by Novartis, the manufacturer of ofatumumab.
Published By :
The Lancet. Haematology
Jul 01, 2020