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Novel immunosuppression triplet confers positive results in primary ITP
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A novel triplet composed of dexamethasone, cyclosporine and low-dose rituximab demonstrated safety and efficacy in patients with primary immune thrombocytopenia, according to study results.
Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia without other causes, according to study background. Single-agent therapies have not conferred prolonged remission and often result in serious adverse events. However, recent studies combining dexamethasone and rituximab (Rituxan, Genentech/Biogen Idec) have demonstrated encouraging results.
Beng H. Chong, MBBS, PhD, professor of medicine at the University of New South Wales and director of hematology at St. George’s Hospital in New South Wales, Australia, and colleagues conducted a pilot study to determine the safety and efficacy of a novel triplet featuring dexamethasone, rituximab and cyclosporine. Researchers hypothesized that the combination may produce lasting remission by targeting T cells and suppressing immune cell types.
The single arm, phase 2b study included 20 patients with ITP. The therapy regimen consisted of 4-week cycles of oral dexamethasone (40 mg) on days 1 through 4, oral cyclosporine (2.5 mg/kg to 3 mg/kg) every day and IV low-dose rituximab (100 mg) on days 7, 14, 21 and 28.
Median follow-up was 17.5 months (range, 7-47).
Sixty percent of patients (n = 12) responded to treatment, and the median time to response was 7.4 days. Thirty percent of patients achieved complete response at 6 months; however, two responding patients relapsed during follow-up.
Ninety-two percent (95% CI, 53-98) of patients who responded to treatment achieved 12-month RFS and 76% (95%, 30-93) achieved 24-month RFS.
Two patients who did not respond to treatment underwent splenectomy. One patient achieved complete response at 5 months and one patient achieved reduction in steroid dependence 3 years after completion.
Four patients who did not respond to treatment did not require further therapy. The researchers observed a 12-month treatment-free survival rate of 75% (95% CI, 49-88).
Subgroups associated with 6-month response rate included male sex (P = .0045), fewer than three prior lines of therapy (P = .0047) and additional platelet response by day 28 (P = .0181) or day 60 (P = .0017).
Between days 7 and 28, peripheral CD4-positive T cells reduced a median 0.41x109/L (P = .0032) regardless of response. However, responders achieved lower T-cell levels at 6 months (median 0.62x109/L vs. 0.91x109/L; P < .0001).
Peripheral CD19-positive B cells became undetectable for all patients by day 28. Patients aged younger than 50 years experienced B-cell recovery at an earlier rate (P = .0015); however, B-cell recovery did not correspond to response status.
Overall, immunoglobulin levels decreased from baseline to 6 months (0.97 g/L; 95% CI, 0.09-3.2). However, researchers did not observe a correlation between immunoglobulin levels and treatment response.
No treatment-related deaths, serious adverse events, treatment interruptions or delays due to toxicity occurred. Four therapy-related grade 3 to grade 4 adverse events occurred, including hypertension (n = 3) and infection (n = 1).
“Protocols utilizing low-dose rituximab will be attractive where funding resources are limited,” Chong and colleagues concluded. “Although our study shows encouraging results, the incremental benefit of cyclosporine to rituximab and dexamethasone remains unresolved and randomized control trials will be required.” – by Cameron Kelsall
Disclosure: Chong reports receiving research funding from and speakers bureau roles with Amgen and GlaxoSmithKline. One other researcher reports receiving speaking fees from Roche.
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