Bendamustine With Dexamethasone in Relapsed/Refractory Systemic Light-Chain Amyloidosis: Results of a Phase II Study

Abstract

Purpose: No established treatments exist for relapsed/refractory systemic light-chain (AL) amyloidosis. Bendamustine has shown potential in the treatment of multiple myeloma. We conducted a phase II, multicenter trial to assess the efficacy and safety of bendamustine with dexamethasone (ben-dex) in patients with persistent or progressive AL amyloidosis after ≥ 1 prior therapy.

Methods: The trial enrolled 31 patients who received bendamustine on days 1 and 2 (100 mg/m2 intravenously) with 40 mg of weekly dexamethasone in 28-day cycles until disease progression or up to 6 cycles after complete hematologic response. The primary objective was the rate of partial hematologic response (PR) or better.

Results: Patients received a median of 4 cycles (range, 2-12 cycles) with 57% of patients achieving a PR or better (11% complete response, 18% very good PR). The overall organ response was 29% among the 24 patients who had measurable organ involvement. Treatment was well tolerated with no grade 5 treatment-related adverse events (AEs). Sixty-five percent of patients had a therapy-related grade 3-4 AE. The most common AEs included myelosuppression, fatigue, and nausea/vomiting. The median overall survival was 18.2 months (95% CI, 11.3 to 43.8 months), and hematologic response was associated with prolonged survival (P = .0291). The median progression-free survival was 11.3 months (95% CI, 5.0 to 15.4 months).

Conclusion: Overall, ben-dex is a viable treatment option with substantial efficacy and limited toxicity for patients with pretreated AL amyloidosis who have limited therapeutic options. This trial was registered at (ClinicalTrials.gov identifier: NCT01222260).

Figures

FIG 1.

(A) Overall survival (OS) from the start of the first cycle of treatment by Kaplan-Meier estimation with 95% CIs (n = 29). (B) Landmark analysis of OS after completion of 2 cycles of treatment, according to hematologic response category: complete response, very good partial response, or partial response (CR/VGPR/PR) versus stable disease/progression of disease (SD/PD). Hematologic response was assessed at cycle 3 day 1, which is the landmark time (n = 28). Survival functions are compared using the log-rank test with a 2-sided P value. NR, not reached.

FIG 2.

Progression-free survival (PFS) from the start of the first cycle of treatment until hematologic disease progression or time of death by Kaplan-Meier estimation with 95% CIs (n = 29).