From the Guidelines
Treatment for amyloidosis, particularly AL amyloidosis, should prioritize daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) as the standard of care for newly diagnosed patients, given its unprecedented high rate of deep hematologic responses. This approach is based on the landmark ANDROMEDA study, which demonstrated a significant improvement in hematologic responses with daratumumab plus CyBorD compared to CyBorD alone 1.
Key Considerations for Treatment
- For patients who are not candidates for stem cell transplantation (SCT), bortezomib-based regimens in combination with dexamethasone and an alkylating agent are recommended, with CyBorD and bortezomib-melphalan-dexamethasone being the most common regimens 1.
- Patients with advanced cardiac involvement may receive single-agent daratumumab with a minimal dose of dexamethasone to minimize potential cardiotoxicity 1.
- Supportive care is essential for all types of amyloidosis and includes diuretics for fluid retention, pain management, and specialized care for affected organs.
- Organ transplantation may be necessary in advanced cases with significant heart, liver, or kidney involvement.
Relapsed/Refractory AL Amyloidosis
- Daratumumab or daratumumab-based therapy is recommended for second-line treatment, given its excellent overall response rate (ORR) and deep remissions 1.
- For third-line treatment, considerations include repeating the original therapy if the patient had a hematological relapse ≥2 years since the last therapy, or using a bortezomib-based regimen if the patient is not bortezomib refractory 1.
- Pomalidomide-dexamethasone (pom-dex) or lenalidomide-dexamethasone (len-dex) can be used in patients who are bortezomib refractory 1.
Emerging Therapies
- Ixazomib and carfilzomib, second-generation proteasome inhibitors, have shown promise in the treatment of AL amyloidosis 1.
- Venetoclax has demonstrated efficacy in patients with t(11;14), a common translocation in AL amyloidosis 1.
- Bendamustine, particularly in combination with rituximab, may be considered for patients with IgM amyloidosis or lymphoplasmacytic histology 1.
- Isatuximab, another anti-CD38 monoclonal antibody, has shown promising efficacy in relapsed/refractory AL amyloidosis 1.
From the FDA Drug Label
VYNDAQEL and VYNDAMAX are transthyretin stabilizers indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. (1) ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
The treatment options for amyloidosis include:
- Tafamidis (PO), a transthyretin stabilizer, for the treatment of cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults 2
- Patisiran (IV), for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults 3
From the Research
Treatment Options for Amyloidosis
The treatment options for amyloidosis are varied and depend on several factors, including the type of amyloidosis, the extent of organ involvement, and the patient's overall health.
- For patients with light chain (AL) amyloidosis, treatment options include:
- High-dose melphalan and stem cell transplantation for carefully selected patients 4
- Bortezomib-based regimens, such as bortezomib, oral melphalan, and dexamethasone (BMDex), or bortezomib, cyclophosphamide, and dexamethasone (CyBorD or VCd) for transplant-ineligible patients 4, 5
- Daratumumab-based regimens, such as subcutaneous daratumumab (DARA SC) and VCd 4
- For patients with relapsed or refractory AL amyloidosis, treatment options include:
- Treatment decisions should be made by a multidisciplinary team, taking into account the patient's functional status, disease stage, degree of organ dysfunction, and potential treatment toxicities 7
- Atypical presentations of AL amyloidosis, such as hepatic AL amyloidosis without significant light chain elevation, can respond to treatment with traditional chemotherapy, daratumumab, and stem cell transplant 8