Ofatumumab plus chlorambucil as a first-line therapy in less fit patients with chronic lymphocytic leukemia: analysis of COMPLEMENT1 and other monoclonal antibodies association data

Abstract

Abstract:The management of patients with chronic lymphocytic leukemia (CLL) has radically improved over the last few years with the addition of anti-CD20 monoclonal antibodies (MoAbs) to chemotherapy. Chlorambucil has been considered for decades as a suitable therapeutic option for frail patients. Taking into account the advantage offered by the addition of MoAbs to chemotherapy, different studies up to now have explored the feasibility of chlorambucilbased chemoimmunotherapies in treatment-naïve CLL. COMPLEMENT1 is a prospective, randomized, open-label trial evaluating the efficacy and safety of ofatumumab added to chlorambucil, compared with chlorambucil in monotherapy, in the setting of untreated patients with CLL considered unsuitable for a fludarabine-based approach. Progression-free survival was significantly longer in the chemoimmunotherapy arm when compared with the single-agent chlorambucil (22.4 months versus 13.1 months). Response rate and quality were also improved in the combination arm. Furthermore, the addition of ofatumumab did not lead to an unmanageable toxicity. While the employment of anti-CD20 antibodies represents an advantage in the treatment of the CLL symptomatic population, at present different patient selection and treatment schedules do not allow a reliable comparison between chlorambucilbased regimens. The addition of ofatumumab to chlorambucil represents a further therapeutic gain in CLL. Longer follow up and direct comparison with other MoAbs are warranted to establish the preferred first-line treatment in elderly and unfit patients.

Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab

“…1 For initial therapy of CLL, treatment approaches have evolved from monotherapy with alkylating agents to chemoimmunotherapy including a CD20 antibody such as rituximab or obinutuzumab. [5][6][7][8] Although a subset of patients with CLL requiring treatment are young or fit with IGHV-mutated disease in which durable remissions can be appreciated with fludarabine, cyclophosphamide, and rituximab (FCR), the majority of patients are not and typically relapse within 3 to 5 years or earlier. 3,9,10 At relapse, treatment often includes different or similar chemoimmunotherapy or targeted agents such as B-cell receptor signaling pathway inhibitors or BCL-2 inhibitors.…”