Initial management of immunoglobulin light chain (AL) amyloidosis Mayo stage I to IIIA

CR: complete response; CyBorD: cyclophosphamide, bortezomib, dexamethasone; DaraCyBorD: daratumumab, cyclophosphamide, bortezomib, dexamethasone; dFLC: difference between involved and uninvolved serum FLC levels; FISH: fluorescence in situ hybridization; FLC: free light chain; HCT: hematopoietic cell transplantation; MGUS: monoclonal gammopathy of undetermined significance; MM: multiple myeloma; SPEP: serum protein electrophoresis; VGPR: very good partial response.

* 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 nonpurpuric cutaneous lesions) do not require systemic therapy.

¶ Transplant eligibility must be determined on an individual basis. Most patients with AL amyloidosis will not be candidates for HCT due to advanced age, kidney impairment, advanced heart failure, or multiorgan involvement.

Δ DaraCyBorD is the preferred induction regimen. If the patient is not a candidate for bortezomib (eg, sensory neuropathy that is painful or limiting self-care), we offer daratumumab as a single agent or in combination with cyclophosphamide and dexamethasone.

◊ For most patients, we aim for a hematologic CR. For some patients, a hematologic VGPR may be sufficient.

§ During treatment, monitor response with monthly serum FLC and SPEP with or without immunofixation. Upon completion of therapy, monitor every 1 to 3 months with FLC and immunofixation (if hematologic CR) or FLC alone (if less than a hematologic CR). We offer alternative systemic therapy if:

• The initial therapy fails to achieve >50% reduction in the dFLC after 2 cycles or dFLC <40 mg/L after 4 to 6 cycles.
• There is disease progression of organ involvement or hematologic progression at any time. Refer to related UpToDate content for further details.

¥ An "early" HCT approach incorporates high-dose melphalan and autologous HCT into the initial treatment. With a "delayed" HCT approach, HCT is deferred until first relapse. A delayed HCT approach is a reasonable option for patients who achieve a hematologic CR and have disease without high-risk plasma cell features or myeloma-like features, including high-risk FISH.

‡ If pretreatment dFLC <50 mg/dL, aim for dFLC <10 mg/dL rather than 40 mg/dL.

† Observation until progression is appropriate for most patients who achieve a hematologic CR and some patients who achieve a VGPR. A hematologic VGPR may not be sufficient for some patients. Consultation with an Amyloid Center of Excellence is advised. Although there are limited data, we offer post-transplant maintenance with lenalidomide or daratumumab to patients with myeloma-like features (eg, high-risk cytogenetics, bone lesions, or high plasmacytosis).