Front-Line Hyper-CVAD Plus Ofatumumab Safe, Effective for Ph-Negative B-Cell ALL

The combination of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) plus ofatumumab is safe and active in adults with Ph-negative CD20-positive B-cell acute lymphoblastic leukemia (ALL), phase 2 study findings confirm (Lancet Haematol. 2020;7[7]:e523-e533).

“In this study, we assessed the activity and safety of ofatumumab in combination with chemotherapy in patients with [Ph]-negative CD20-positive B-cell [ALL],” wrote Elias Jabbour, MD, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, and co-investigators, who enrolled 69 patients (median age, 41 years) in the single-arm clinical trial between August 26, 2011, and May 18, 2017.

Among the patients in the study, 67 had B-cell ALL and 2 had B-cell lymphoblastic lymphoma; 9 (27%) of 33 patients had Ph-like ALL.

All participants were given up to 8 courses of hyper-CVAD on courses 1, 3, 5, and 7 alternating with high-dose methotrexate and cytarabine on courses 2, 4, 6, and 8. Patients also received ofatumumab on days 1 and 11 of courses 1 and 3 and on days 1 and 8 of courses 2 and 4 for a total of 8 doses (first dose, 300 mg and all subsequent doses, 2000 mg).

The primary end points of the study were event-free survival, overall response, and overall survival.

According to the findings, the median follow-up time frame was 44 months, and the 4-year event-free survival rate was 59% (95% CI, 48-73). The 4-year overall survival rate was 68% (95% CI, 58-81), and the overall response rate was 98%.

Infections were the most common nonhematologic grade 3 or 4 adverse event, and while 10 (14%) patients died in complete remission, none of the deaths were deemed related to ofatumumab therapy by the investigators.

“The combination of hyper-CVAD plus ofatumumab is safe and active in adults with Ph-negative CD20-positive B-cell [ALL],” Dr Jabbour and colleagues wrote.

“Modifications of this regimen with the addition of novel monoclonal and bispecific antibody constructs targeting CD19 and CD22 might further improve outcomes and allow reduction in the intensity and duration of chemotherapy,” they concluded.—Hina M. Porcelli