Further line treatment of patients with advanced stage AL amyloidosis with cardiac involvement is challenging. Venetoclax is a promising option, especially in t(11;14) and BCL2 expression.
In our multicentre observational study, we report the 3-year follow-up of Venetoclax treatment in 9 patients with advanced, relapsed or refractory AL amyloidosis with t(11;14) and BCL-2 expression in > 50% of plasma cells. At baseline, all patients had been previously treated with daratumumab, all had cardiac involvement with revised Mayo stage III or IV/ European modification of Mayo 2004 IIIA or IIIB (1/9 unclassified due to missing troponin T), 5/9 patients had renal involvement.
After a median of 35 months (range 25–49) since the start of Venetoclax, 8/9 patients were still alive (OS 89%). First and best hematological responses were observed after a median of 26 days (11–125) and 106 days (35–659), overall response rate was 100% (7/9 CR, 2/9 VGPR). Where observed, organ response was documented within the first 6 months of therapy, including cardiac (6/9) and renal (3/5) improvements. Venetoclax was discontinued in 6/9 patients after a median of 15 months (11–48) due to toxicity (2/9), disease progression (2/9), fixed treatment duration (1/9), or safety concerns (1/9).
In conclusion, Venetoclax induces a rapid and deep hematologic response with consistent improvement in organ function with an acceptable safety profile in patients with pretreated, advanced stage AL amyloidosis with cardiac involvement and BCL2 expression with and potentially without detected t(11:14), which warrants further investigation.
