Venetoclax shows promise in relapsed/refractory light-chain amyloidosis

Venetoclax-containing regimens seem effective for patients with relapsed/refractory light-chain amyloidosis (AL), a recent study has found.

The researchers conducted a retrospective assessment of 43 patients (median age, 66 years; 65 percent male) who had previously undergone treatment with a venetoclax-containing regimen for RR AL. Those whose treatment lasted for 21 or 28 days were eligible for analysis. Outcomes included overall survival (OS), progression-free survival (PFS), and very good partial or complete response (VGPR/CR) rate.

All patients underwent a median of three prior lines of therapy. Most of the regimens combined venetoclax with glucocorticoids and/or proteasome inhibitors; venetoclax doses ranged from 100 to 800 mg daily. Seventy-two percent of the participants had the t(11;14) cytogenetic abnormality of amyloidosis.

Forty-two patients were evaluable for PFS and OS. After a median follow-up of 14.5 months, the researchers obtained a median PFS estimate of 31.0 months, while OS was not reached. The respective 12-month estimates were 78 percent and 93 percent. Outcomes were better for the t(11;14) patients, with 12-month PFS and OS of 90 percent and 97 percent, respectively.

Thirty-eight patients had available response rate information for analysis. The VGPR/CR rate in these patients was 63 percent, and the median time to best response was 8.5 weeks. In t(11;14)-positive patients, VGPR/CR was 78 percent.

For all outcomes, patients harbouring t(11;14) tended to fare better, showing an 86-percent drop in the risk of progression or death compared to those without the translocation, and an 88-percent greater likelihood of achieving VGPR/CR.

“[T]he results of our multi-institutional study indicate a strong rationale toward a biomarker-driven approach for AL patients. Though our findings demonstrate the efficacy of venetoclax in the RR setting, they additionally serve as a platform for targeted treatment in newly diagnosed t(11;14) AL,” the researchers said.

“Larger prospective studies are required to validate our findings that promote a new and convenient therapeutic approach, with a manageable toxicity profile and the potential to favourably alter the clinical course of AL,” they added.