Rescue therapy with pomalidomide in combination with dexamethasone is a rapidly active regimen among heavily pretreated patients with amyloid light-chain (AL) amyloidosis, including those who have previously been exposed to alkylators, proteasome inhibitors, and lenalidomide, according to a study published in Blood.1
Although immunomodulatory drugs like lenalidomide and pomalidomide are active in AL amyloidosis, previous studies were unable to demonstrate a survival benefit among patients with AL amyloidosis responding to salvage therapy with pomalidomide.
In this open-label, phase 2 trial (ClinicalTrials.gov Identifier: NCT01510613), investigators enrolled 28 heavily pretreated patients with AL amyloidosis to evaluate the safety and efficacy of pomalidomide plus dexamethasone rescue therapy. Patients received oral pomalidomide continuously and dexamethasone weekly.
Results showed that 68% (95% CI, 49-83) of patients achieved a hematologic response, including 29% who had a very good partial or complete response. Median time to response was 1 month.
Investigators observed hematologic responses in 86% of the 7 patients who received prior lenalidomide and in 75% of the 4 patients exposed to ixazomib.
Median progression-free survival and overall survival were 16 months and 26 months, respectively. Hematologic response was associated with improved overall survival (P = .001).
More than half of patients had grade 3 to 4 adverse events, with the most common being fluid retention, infection, atrial fibrillation, and deep vein thrombosis. Nearly 30% of patients discontinued treatment due to adverse events.
The findings suggest that pomalidomide plus dexamethasone is an efficacious rescue strategy in relapsed/refractory AL amyloidosis. Studies investigating pomalidomide in combination with other agents as upfront treatment are warranted.
- Palladini G, Milani P, Foli A, et al. A phase II trial of pomalidomide and dexamethasone rescue treatment in patients with AL amyloidosis. Blood. 2017 Jan 27. doi: 10.1182/blood-2016-12-756528 [Epub ahead of print]