Initial management of AL amyloidosis

AL: amyloid light chain; HCT: hematopoietic cell transplantation; dFLC: difference between involved and uninvolved serum FLC levels; FLC: free light chain; MGUS: monoclonal gammopathy of undetermined significance; MM: multiple myeloma; BMD: bortezomib, melphalan, dexamethasone; CyBorD: cyclophosphamide, bortezomib, dexamethasone; SPEP: serum protein electrophoresis.
* Virtually all patients with systemic AL amyloidosis require treatment at the time of diagnosis. An important exception is patients with AL amyloid in the bone marrow discovered incidentally as part of the evaluation of MGUS or smoldering MM in whom initial therapy can be postponed until the first sign of organ involvement. Localized forms of amyloidosis (eg, tracheobronchial, genitourinary, isolated carpal tunnel, and non-purpuric cutaneous lesions) do not require systemic therapy.
¶ Transplant eligibility must be determined on an individual basis. The majority of patients with AL amyloidosis will not be candidates for HCT due to advanced age, renal insufficiency, advanced heart failure, or multiorgan involvement.
Δ Preferred bortezomib-based regimens for HCT-eligible patients are Dara-CyBorD or CyBorD. BMD is an acceptable alternative for patients not eligible for HCT.
◊ Assess response monthly with serum FLC assay and SPEP with or without immunofixation.
§ Progression of organ involvement or hematologic progression should lead to alternative therapy. Hematologic progression is detected by an FLC increase of 50% to >100 mg/L. If prior studies demonstrated normalization of the FLC levels and ratio with negative serum and urine immunofixation, progression can be identified by any detectable M protein or abnormal FLC ratio (light chain must be double).
¥ Standard dose for HCT is melphalan 200 mg/m². This dose is reduced to 140 mg/m² in patients on chronic stage dialysis.
‡ If pretreatment dFLC <50 mg/L, aim for dFLC <10 mg/L rather than 40 mg/L.
† We follow patients monthly for the first year with serum FLC assay and SPEP with or without immunofixation.