Anti-CD20 monoclonal antibody ofatumumab in combination with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) is a safe and active frontline treatment for adults with Philadelphia chromosome (Ph)-negative, CD20-positive B-cell acute lymphoblastic leukemia (ALL), according to study results reported in The Lancet Haematology.
Elias Jabbour, MD, and associates conducted an open-label phase 2 trial (ClinicalTrials.gov Identifier: NCT01363128) at the MD Anderson Cancer Center in Houston, Texas. A total of 69 patients were administered 8 doses of ofatumumab and 4 courses of hyper-CVAD in alternation with 4 courses of high-dose methotrexate and cytarabine, for induction and consolidation. The primary endpoints included event-free survival (EFS), overall response rate (ORR), and overall survival (OS).
Nearly the entire cohort (67 patients; median age, 41 years; 58% men) had B-cell ALL; the remaining 2 patients had B-cell lymphoblastic lymphoma. By the median follow-up of 44 months, 67% of patients survived and slightly more than half (54%) of patients were in first complete remission.
The 4-year EFS rate was 59%, with a median EFS of 51 months. The 4-year OS rate was 68%, with a median OS that was not reached. Adolescents and young adults had a 4-year EFS rate of 69% and a 4-year OS rate of 74%, as determined in post-hoc subgroup analyses. Nearly all patients in the study responded, with an ORR of 98%.
Grade 3 to 4 infections were reported in 54% of patients receiving induction and in 78% receiving consolidation therapy. Some additional grade 3 to 4 adverse events included hyperglycemia, hypokalemia, and increased aminotransferases. Deaths reported among patients in complete remission were related to complications of hematopoietic stem cell transplantation (7%), sepsis (3%), therapy-associated acute myeloid leukemia (3%), and cardiac arrest (1%). There was 1 fatality during induction related to an infection.
“In summary, the combination of hyper-CVAD plus ofatumumab is safe and active as a frontline treatment for patients with Ph-negative CD20-positive B-cell acute lymphoblastic leukaemia,” concluded the study investigators in their report. The investigators also suggested that CD19- and CD22-directed agents may be useful in treatment of this patient population.
Disclosure: Some of the authors disclosed financial relationships with pharmaceutical companies and medical device manufacturers. For a full list of disclosures, please refer to the original study.
Jabbour E, Richard-Carpentier G, Sasaki Y, et al. Hyper-CVAD regimen in combination with ofatumumab as frontline therapy for adults with Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia: a single-arm, phase 2 trial. Lancet Haematol. 2020;7(7):e523-e533.