NEW YORK (Reuters Health) - Ofatumumab, a new fully human anti-CD20 monoclonal antibody, is well tolerated by patients with chronic lymphocytic leukemia (CLL) in doses up to 2,000 mg. These results of a European-American dose-escalating study support further studies on ofatumumab, according to a report in the February 1 issue of Blood.
Ofatumab, un nouvel anticorps monoclonal est bien toléré chezles patints atteints de CLL jusqu'à des doses de 2,000 mg. ces résultats proviennent d'une étude européenne/américaine sur l'ofatumumab
The open-label phase 1/2 trial was the first study of ofatumumab in relapsed or refractory patients with CLL. It was conducted at 12 centers in Europe and the United States and involved 3 cohorts, all of whom received 4 weekly infusions of ofatumumab. The 3 patients in cohort A received an initial infusion of 100 mg, followed by 3 infusions of 500 mg. The 3 patients in cohort B received an initial infusion of 300 mg, followed by 3 of 1,000 mg. The 27 patients in cohort C received a first infusion of 500 mg and three subsequent infusions of 2,000 mg.
Cette phase 1 et 2 des essais cliniques est la première sur l'ofatumab sur les patients avec CLL réfractaire.
The majority of adverse events were mild. Most (138/246, or 56%) occurred on an infusion day, and 84 were reported on the day of first infusion. Ten adverse events were serious; these included neutropenia, herpes zoster, pneumonia and hemolytic anemia. There was 1 fatality in an 82-year-old man with profound chronic hypogammaglobulinemia and infectious interstitial lung disease. Infections were reported in 51% of patients; nasopharyngitis was the most common.
The remission rate in cohort C was 50% (95% CI: 30-70%). There were no complete remissions, but 12 patients in cohort C (the highest-dose group) and 1 in cohort A had partial remissions, and 1 additional patient in cohort C had a nodular partial remission. Not all responses were sustained, however. At week 19, only 9 patients showed sustained responses.
Le taux de rémission dans la cohorte C était de 50%. Il n'y a pas eu de complètes rémissions mais 12 patients dans la cohorte C et 1 dans la cohorte A ont eu des rémissions prtielles.
The researchers caution that "this relatively small phase 1/2 study is not sufficient to definitively conclude that ofatumumab is superior" to rituximab, which is often used in progressing patients. They also note, however, that in vitro data suggest ofatumumab would be superior in relapsing CLL patients.
Les chercheurs disent que cette relativement petite étude ne suffit pas à conclure définitivement que l'ofatumumab serait supérieur à rituximab qui est souvent utilisé. Il snotent toutefois que invitro l'ofutomab serait supérieur.
Dr. Bertrand Coiffier, of the Centre Hospitalier Lyon Sud, Pierre-Benite Cedex, France, told Reuters Health he is optimistic about ofatumumab. "This antibody is different from rituximab," he explained. "It targets different epitopes from the CD20 antigen, it has different pharmacokinetics on the cell surface (longer exposition), and it has better activity on CLL cells in vitro."
Le docteur Bertrand Coiffierdu Centre hositalier de Lyon se dit optimiste.