What is the treatment approach for patients with kappa lambda free light chains (FLC) cardiac amyloidosis?

From the Guidelines

The treatment approach for patients with kappa or lambda free light chain (FLC) cardiac amyloidosis, also known as AL amyloidosis, involves a combination of supportive care and targeted therapy to reduce the production of amyloidogenic light chains, with daratumumab-CyBorD emerging as the standard of care for newly diagnosed AL amyloidosis, as shown in the 2023 ACC expert consensus decision pathway 1.

Treatment Overview

The cornerstone of treatment is chemotherapy regimens similar to those used for multiple myeloma, typically including a proteasome inhibitor (bortezomib), an immunomodulatory drug (lenalidomide), and dexamethasone.

• A common first-line regimen is CyBorD (cyclophosphamide, bortezomib, and dexamethasone), administered in 28-day cycles.
• For eligible patients under age 65-70 with good performance status and limited organ involvement, high-dose melphalan (200 mg/m²) followed by autologous stem cell transplantation may be considered.

Supportive Care

Supportive care is crucial and includes:

• Diuretics for fluid management
• Salt restriction
• Careful blood pressure control
• ACE inhibitors and angiotensin receptor blockers should be used cautiously as they may cause hypotension

Treatment Response

Treatment response is monitored through serum free light chain assays, with the goal of achieving a complete hematologic response or very good partial response.

• Early diagnosis and prompt initiation of therapy are essential as cardiac involvement significantly impacts prognosis in AL amyloidosis, as noted in the European Myeloma Network recommendations 1.

Newer Agents

Newer agents like daratumumab (anti-CD38 monoclonal antibody) are showing promise when added to standard regimens, with a high rate of deep hematologic responses in the ANDROMEDA study 1.

• The use of daratumumab-CyBorD has been approved by the FDA and the European Medicines Agency for treatment of newly-diagnosed AL amyloidosis.

From the Research

Treatment Approach for Kappa Lambda Free Light Chains Cardiac Amyloidosis

• The treatment approach for patients with kappa lambda free light chains (FLC) cardiac amyloidosis involves therapies aimed at reducing the production of amyloidogenic light chains, such as cyclophosphamide, bortezomib, and dexamethasone (CVD) 2, 3.
• The goal of therapy is to achieve a rapid and meaningful reduction in circulating light chains while maximizing patient safety, which can be challenging due to organ dysfunction and increased treatment toxicity 4.
• Autologous stem cell transplantation (ASCT) may be considered in eligible patients, while standard-intensity therapies can be used in a risk-adapted approach 4.
• Optimization of serum immunoglobulin free light chain analysis can help differentiate immunoglobulin light chain amyloid (AL) amyloidosis from other types of cardiac amyloidosis, guiding treatment decisions 5.
• Early diagnosis and treatment are crucial, as cardiac amyloidosis can lead to sudden death, with ventricular arrhythmia and heart failure being major risks 6.

Response Assessment and Organ Involvement

• Response assessment, including organ response, is essential in managing patients with AL amyloidosis, with guidance on response evaluation provided in the literature 4.
• Cardiac involvement is a major determinant of short- and long-term survival, and treatment should be tailored to address cardiac dysfunction 4, 6.
• The serum free light chain kappa/lambda ratio can be used to differentiate AL amyloidosis from non-AL amyloidosis, with a ratio between 0.5 and 5.0 having high sensitivity and specificity 5.

Challenges and Future Directions

• Managing patients with AL amyloidosis poses challenges due to organ dysfunction, treatment toxicity, and the need for a multidisciplinary approach 4.
• Recent data suggest that cardiac amyloidosis has become a treatable and curable condition with a combination of agents targeting multiple steps of the amyloid cascade 6.
• Further research is needed to improve treatment outcomes and address the challenges associated with managing patients with kappa lambda free light chains cardiac amyloidosis.