Rituximab Plus Pulse Dexamethasone Effective, Tolerable in Patients with Immune Thrombocytopenia
SAN DIEGO, CA—Standard-dose rituximab plus multiple courses of pulse dexamethasone was shown to be active with manageable toxicity in patients with immune thrombocytopenia (ITP), according to results of a retrospective analysis presented during the 53rd American Society of Hematology Annual Meeting and Exposition. In addition, results appeared superior to either agents alone compared with historical controls.
For patients with ITP, rituximab has been a useful treatment, with 30–40% achieving a complete remission (CR) that will last at least a year in almost all. Emerging data suggests, however, that at least 40% will relapse between one and three years, with long-term “cures” occurring in only 20%. For this reason, increased rate of durable CR is a desirable goal. In patients with newly diagnosed ITP, one study found a single, 4-day course of high-dose (40mg/day) dexamethasone to be effective, while another demonstrated increased efficacy of multiple dexamethasone courses; a third study found rituximab with a single course of dexamethasone to be superior to dexamethasone alone in previously untreated patients.
Based on these data, patients with ITP at Weill Cornell Medical College, New York, NY, are treated with rituximab and dexamethasone. Results of 14 patients treated with this combination have previously been reported; to provide a broader evaluation of efficacy and safety of the regimen, Rebecca L. Elstrom, MD, and colleagues from Weill Cornell Medical College and Albert Einstein College of Medicine, NY, studied 38 retrospectively identified patients who had been treated with rituximab and three cycles of pulse dexamethasone at approximately 2-week intervals.
CR was defined as platelet count ≥100x109/L and partial remission (PR) as a platelet count of 50–100x109/L at six to eight weeks after treatment. Chi-square or Fisher exact test were used to compare variables such as duration of ITP (greater than or less than 1 year), age, prior therapy, and lymphocyte subsets. Patients were treated if platelet counts were <30x109/L or they were unable to discontinue chronic therapy such as corticosteroids or thrombopoietin receptor agonist.
Median age was 21 years (range 2–63); median time since diagnosis of ITP was 12 months (range 1–180). The median number of prior therapies was two (range 0–7). Of the 38 patients, 36 received four infusions of standard dose rituximab and two patients received two infusions. All received between one and four cycles of dexamethasone (median, 3 cycles).
Short-lived platelet increases in response to dexamethasone were observed in almost all patients. Overall response was 70%, with 26 patients responding. Best response was CR in 22 (59%) and PR in four patients (11%); 12 patients did not respond. At a median follow-up of 14 months, response was maintained in 22 patients (59%). The most commonly reported toxicities included hyperglycemia, Grade 1 and 2 liver function abnormalities, weight gain, and colitis (1 episode).
These data suggest a regimen of rituximab plus 1–4 courses of dexamethasone is active in patients with ITP and that toxicity, while appreciable, is usually manageable. The investigators concluded that this combination merits further exploration in a prospective clinical trial.