【Introduction】Patients with amyloid light-chain (AL) amyloidosis who have advanced cardiac damage are at risk of premature mortality. Currently, bortezomib is the mainstay in the treatment of AL amyloidosis, but the benefits of bortezomib in patients with ultra-high-risk AL amyloidosis have not been proved definitively. In current study, we aimed to establish the effects of bortezomib on early mortality, treatment responses and long-term outcomes in this very high-risk population.

【Methods】We performed a retrospective analysis of patients newly diagnosed with ultra-high-risk (defined by 2004 Mayo Stage IIIb or 2012 Mayo stage IV criteria) AL amyloidosis who received a bortezomib-based regimen or supportive treatment from January 1, 2009 to April 1, 2018 in our hospital. Kaplan-Meier survival curves were plotted. Between-group comparisons of progression-free survival (PFS) and overall survival (OS) were conducted with the log-rank test. To examine the impact of treatment on patients who survived long enough to have potentially benefited from therapy, a 6-month landmark analysis was performed among patients surviving at least 6 months from the start of treatment.

【Results】Patients receiving bortezomib-containing chemotherapy (n = 62) and patients receiving no chemotherapy (n = 24) were included. The overall median age at presentation was 59 years (range 37-81 years), with a male: female ratio of 2.2:1. Organ involvement included the heart (100%), kidney (68.6%) and liver (25.6%). The median number of chemotherapy cycles was four (range 1-12). The overall hematological response rate in the bortezomib group was 59.3%, with 42.6% achieving a complete response, 7.4% having a VGPR. A cardiac response was observed in 36.7% of patients. With an overall median follow-up of 24.3 months, median OS was 30 months in the bortezomib group and 2 months in the control group (p < 0.001) (Figure 1-A), and median PFS was 15.8 months (bortezomib) and 2 months (control; p < 0.001) (Figure 1-B). The early-death rate (within 6 months of diagnosis) was 32.3% (bortezomib) and 66.7% (control; p < 0.001). In a landmark analysis assessing outcomes in patients surviving beyond 6 months, the 2-year OS and PFS in the bortezomib group were 77.3% and 65.8%, respectively.

【Conclusions】Bortezomib-based regimens can help to reduce early mortality and improve long-term survival in patients with ultra-high-risk AL amyloidosis, especially in those who achieve a threshold hematological response. We recommend that both physicians and patients should always consider chemotherapy, regardless of the disease stage, as long as treatment-related complications are controllable.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.