Ofatumumab added to dexamethasone in patients with relapsed or refractory chronic lymphocytic leukemia: Results from a phase II study

Abstract

The treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) remains a challenging clinical issue. An important treatment option is the use of high-dose corticosteroids. The purpose of this clinical trial was to determine the efficacy and toxicity of an ofatumumab-dexamethasone (O-Dex) combination in relapsed or refractory CLL. The trial was an open-label, multicenter, nonrandomized, Phase II study. The O-Dex regimen consisted of intravenous ofatumumab (Cycle 1: 300 mg on day 1, 2,000 mg on days 8, 15, and 22; Cycles 2-6: 1,000 mg on days 1, 8, 15, and 22) and oral dexamethasone (40 mg on days 1-4 and 15-18; Cycles 1-6). The ODex regimen was given until best response, or a maximum of six cycles. Thirty-three patients (pts) were recruited. Twenty-four (73%) pts completed at least three cycles of therapy. The remaining nine pts were prematurely discontinued owing to Grade 3/4 infections (seven pts), disease progression (one pt), or uncontrollable diabetes mellitus (one pt). Overall response rates/complete remissions (ORR/CR) were achieved in 22/5 pts (67/15%). The median progression-free survival (PFS) was 10 months. In pts with p53 defects (n 5 8), ORR/CR were achieved in 5/2 pts (63/25%) with a median PFS of 10.5 months. The median overall survival (OS) was 34 months. The Grades 3-5 infectious toxicity in 33% of pts represented the most frequent side effect during the treatment period. In conclusion, the O-Dex regimen shows a relatively high ORR and CR with promising findings for PFS and OS.

Assessment of the efficacy of ofatumumab in patients with chronic lymphocytic leukaemia treated in the Department of Haematooncology and Bone Marrow Transplantation of the Medical University in Lublin – Prelimary results

“…In this case, ofatumumab was combined with cyclophosphamide and dexamethasone, which probably had a positive effect on the treatment results. Synergistic action of ofatumumab and dexamethasone with high response rates and good tolerability were also reported by Castro et al and Doubek et al [12]. Attempts are now being made to combine ofatumumab with other drugs, such as bendamustine [13] or lenalidomide [14].…”

Ofatumumab for the treatment of chronic lymphocytic leukemia

“…The median OS was 34 months. The grade 3-5 infectious toxicity was noted in 33% cases [22]. It must be underlined that combinations of ofatumumab with steroids can be useful especially for patients who are unable to tolerate more aggressive therapies, or have not responded to other treatments [21,22].…”

“…Recently, two Phase II studies on the combination of ofatumumab with steroids in patients with refractory/relapsed CLL were published [21,22].…”

“…In February 2015, promising results of ofatumumab in combination with dexamethasone (O-Dex) in 33 patients were published [22]. The O-Dex regimen was given until best response, or a maximum of six cycles.…”

Monoclonal Antibodies in the Treatment of Chronic Lymphocytic Leukemia in 2015

“…Defi nitivní závěry této studie ještě nejsou k dispozici. Ofatumumab lze stejně jako rituximab kombinovat také s vysokodávkovanými kortikoidy [26].…”