Management of relapsed/refractory AL amyloidosis

Area of Science:

• Hematology
• Oncology
• Immunotherapy

Background:

• Frontline therapy for systemic light chain (AL) amyloidosis has advanced with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCD).
• This regimen has improved hematologic and organ response rates in AL amyloidosis patients.
• However, disease relapse remains a challenge, with no standard salvage therapy established.

Purpose of the Study:

• To review optimal timing for salvage regimens in AL amyloidosis.
• To discuss therapeutic options following daratumumab failure.
• To explore emerging treatments for relapsed AL amyloidosis.

Main Methods:

• Literature review of current and emerging therapies for AL amyloidosis.
• Analysis of treatment strategies following daratumumab-based frontline therapy.
• Examination of salvage options including novel agents and cellular therapies.

Main Results:

• Daratumumab-based therapy offers improved frontline outcomes but eventual relapse necessitates salvage strategies.
• No standard salvage regimen or optimal timing is currently established for daratumumab failure.
• A range of options exist for salvage, including next-generation proteasome inhibitors, immunomodulatory drugs, stem cell transplant, BCL-2 inhibitors, CAR-T therapy, and bispecific antibodies.

Conclusions:

• Effective frontline therapy for AL amyloidosis has been established, but salvage remains critical.
• Further research is needed to define optimal salvage regimens and timing after daratumumab failure.
• Emerging immunotherapies show promise for treating relapsed and refractory AL amyloidosis.