RAISE: Eltrombopag therapy produced benefits in chronic adult ITP

50th ASH Annual Meeting

Patients in the RAISE trial assigned to eltrombopag had significantly increased platelet counts, decreased bleeding symptoms, reduced or discontinued use of idiopathic thrombocytopenic purpura therapies, and reduced use of ITP rescue medications compared to patients assigned to placebo.

Gregory Cheng, MD, of the Chinese University of Hong Kong, presented the results of the study at the 50th Annual Meeting of the American Society of Hematology. “Change has probably come to the treatment of ITP for patients that are refractory to conventional therapy or suffering from a lot of side effects,” Cheng said during a press briefing. “There is now new hope and a new treatment alternative.”

RAISE was a placebo-controlled, double blind, randomized phase-3 study. Researchers assigned 197 patients with chronic ITP and platelet counts <30,000 mcL in a 2:1 ratio to eltrombopag (Promacta, GlaxoSmithKline) or placebo. The primary endpoint was the odds of responding during the six-month treatment period.

Patients assigned to eltrombopag were eight times more likely to achieve target platelet counts ranging from 50,000 mcL to 400,000 mcL (95% CI, 4.32-15.38). Seventy-five percent of patients on eltrombopag achieved the target rate as opposed to 25% of patients in the placebo group.

Patients assigned to eltrombopag had 65% reduction in WHO grade 2-4 bleeding events. The response was seen across all patients groups irrespective of splenectomy status, use of concomitant ITP medication, or whether their baseline platelet count was <15,000.

More patients in the eltrombopag group were able to stop or reduce their dose of concomitant ITP medication compared with the placebo group (59% vs. 32%; P=.016), and these patients required less rescue medication than the placebo group (19% vs. 40%; P=.001). – by Leah Lawrence

For more information:
Cheng G. #400. Presented at: 50th Annual Meeting of the American Society of Hematology; Dec. 5-9, 2008; San Francisco.

In chronic idiopathic thrombocytopenic purpura, the decreased platelet count arises by two distinct mechanisms – accelerated platelet destruction and impaired platelet production, both induced by antibodies targeted to specific glycoproteins on platelets and megakaryocytes. Therapeutic strategies for ITP over several decades have focused on approaches to ameliorate the enhanced platelet destruction. The recent availability of agents eltrombopag and romiplostim that activate the thrombopoietin receptor and stimulate platelet production has opened an entirely novel approach in these patients. Cheng et al report results of a phase III double-blind, placebo-controlled study (RAISE) using eltrombopag, administered daily orally for six months, in 197 previously treated chronic ITP patients with platelet counts less than 30,000/mcL. The results show an impressive eight times greater likelihood of platelet counts greater than 50,000/mcL in the eltrombopag arm, with increase in platelet counts observed from a week of therapy and sustained over a six-month duration. Of particular note, this beneficial response was noted regardless of splenectomy status and was associated with significantly lesser bleeding than in the placebo group. This study extends in a major way the findings of the previously published studies with eltrombopag with treatment duration of six weeks. A higher incidence of elevated serum liver enzymes was observed in patients receiving eltrombopag (13% vs. 7% in placebo) and this needs to be pursued in future studies, including in the context of a longer duration of drug administration than six months. The impressive results of this well-designed study provide strong support for the use of thrombopoiesis-stimulating agents in patients with chronic ITP. Future studies are needed to define their role and place in the overall therapeutic algorithms in chronic ITP patients, including previously untreated patients.

– A. Koneti Rao, MD

HemOnc Today Editorial Board member