Immunoglobulin light chain (AL) amyloidosis is the most common type of systemic amyloidosis. AL amyloidosis is considered a plasma cell disorder caused by generally small and slowly proliferating clone of plasma cells in bone marrow that produces nonfunctional immunoglobulins.

Considering diagnosis of systemic amyloidosis is to evaluate for the presence of monoclonal paraprotein with electrophoresis and immunofixation of both serum and urine, serum kappa and lambda free light chain (FLC) levels, 24-hour urine protein. If testing confirms presence of a monoclonal immunoglobulin or abnormal FLC ratio, then tissue biopsy necessary for diagnosis should be performed. If amyloid is detected in the biopsy, the type of amyloid must be determined for a complete diagnosis.

The most frequently used staging system is the Mayo 2012 model, which assigns a score of 1 for troponin T (≥0.025 μg/L), N-terminal probrain natriuretic peptide (NT-pro BNP; ≥1800ng/L) or BNP ≥400 ng/L, and a difference in serum FLCs (dFLC ≥180 mg/Land is believed to be superior at identifying very high risk individuals (1). An alternative model with high prediction performance is the European 2015 modification of the Mayo 2004 model assigning a score of 1 for troponin T (≥0.035 μg/L), NT-proBNP (≥ 332ng/L) and for stage 3 patients uses the absence or presence of ≥1800 ng/L criteria for IIIA, IIIB designation, respectively (2).

Induction Therapy for Newly Diagnosed AL Amyloidosis:

Many clinical studies investigated the role of bortezomib-based regimens, which were eventually accepted as the standart of care, the most commonly used regimen is combination of CyBorD. With the completion of the phase III Andromeda trial, the treatment paradigm has started to the addition of daratumumab together with CyBorD in the upfront setting.

For patients who are eligible for autologous stem cell transplantation (ASCT), recommended beginning with induction therapy with daratumumab-CyBorD for two to four cycles and then evaluate the response. In patients who achieve a hematological very good partial response (VGPR) or better, forego ASCT and associated treatment-related morbidity and mortality in favor of completion of daratumumab-CyborD induction, followed by daratumumab maintenance for a total of 2 years.

Lack of consensus on optimal use of ASCT in patients with AL amyloidosis. A randomized phase II study involving 91 patients comparing high-dose intravenous melphalan (HDM) followed by ASCT with a course of oral melphalan 10 mg/m2 given once daily and dexamethasone 40 mg given once daily for the first 4 days of a 28 day cycle for up to 18 cycles. At a median follow-up of 3 years, median overal survival (OS) in the HDM arm was significantly worse than those taking high dose melphalan and dexamethasone (22.2 versus 56 months). Clinical studies using modern induction regimens and strict selection criteria emphasize an improved outlook on early survival outcomes in transplantation. . The HOVON104 study evaluated ASCT after four cycles of bortezomib-based induction in 50 patients reported an estimated 3-year OS in the 86% and 72% cardiac response rate in evaluable patients at 2 years.