From the Guidelines
The initial treatment approach for patients with Amyloid Light-chain (AL) Amyloidosis, especially those with impaired organ function, typically involves combination chemotherapy targeting the underlying plasma cell dyscrasia, with the standard first-line regimen consisting of bortezomib, cyclophosphamide, and dexamethasone (CyBorD), as recommended by recent studies 1. The choice of treatment is guided by the patient's risk status, with low-risk patients eligible for transplant considered for melphalan, cyclophosphamide, and bortezomib, while intermediate and high-risk patients may receive bortezomib-based combinations or dose-adjusted treatments 1. Key considerations in treatment include:
- Dose adjustments based on organ dysfunction, particularly for patients with severe cardiac involvement (Mayo stage III/IV) 1
- Supportive care, including diuretics, salt restriction, and monitoring of renal function, as well as prophylaxis against infections and neuropathy 1
- The use of novel agents, such as daratumumab, which has shown promising efficacy in relapsed/refractory AL amyloidosis 1
- The potential for autologous stem cell transplantation (ASCT) in eligible patients, which can improve outcomes 1 Treatment outcomes are closely monitored, with response assessment after 3 cycles and adjustments made as needed to achieve deep, durable responses and prevent relapse/refractory disease 1. Overall, the goal of treatment is to reduce the production of misfolded proteins that deposit in tissues and cause organ damage, thereby improving morbidity, mortality, and quality of life for patients with AL amyloidosis 1.
From the Research
Initial Treatment Approach for Amyloidosis
The initial treatment approach for patients with Amyloid Light-chain Amyloidosis, particularly those with impaired organ function, involves the use of various chemotherapy regimens.
- The combination of oral melphalan and dexamethasone (M-Dex) is considered a standard therapy for patients with light-chain amyloidosis ineligible for autologous stem cell transplantation 2.
- A study published in 2010 reported that treatment with intravenous M-Dex as first-line therapy resulted in a median overall survival of 17.5 months, with 44% of patients achieving hematologic response and 25% achieving organ response 3.
- Another study published in 2007 compared high-dose melphalan with autologous stem-cell rescue to standard-dose melphalan plus high-dose dexamethasone, and found that the latter regimen resulted in a longer median overall survival (56.9 months vs 22.2 months) 4.
Risk-Adapted Approach
A risk-adapted approach to treatment has been proposed, with patients being stratified into different risk groups based on factors such as cardiac and renal function, and free light chain burden.
- A study published in 2014 reported that the combination of oral melphalan and dexamethasone granted extended survival with minimal toxicity in AL amyloidosis, with a median survival of 7.4 years in the full-dose group and 20 months in the attenuated-dose group 5.
- The use of bortezomib in combination with melphalan and dexamethasone has also been investigated, with one study reporting a higher rate of complete responses with this regimen, although this did not result in a survival improvement in the overall population 6.
Treatment Outcomes
The treatment outcomes for patients with Amyloid Light-chain Amyloidosis vary depending on the regimen used and the patient's risk group.
- A study published in 2004 reported that the combination of melphalan and high-dose dexamethasone was effective and well tolerated in patients with AL amyloidosis who were ineligible for stem cell transplantation, with 67% of patients achieving a hematologic response and 33% achieving a complete remission 2.
- The addition of bortezomib to melphalan and dexamethasone has been shown to be beneficial in certain patient populations, such as those without severe heart failure and with N-terminal pro-natriuretic peptide type-B <8500 ng/l 6.