Monitoring Patients with Light Chain (AL) Amyloidosis during and after Therapy: Response Assessment and Identification of Relapse

M. Teresa Cibeira,Paolo Milani

doi:10.3390/hemato3010008

Abstract

Light chain amyloidosis is a complex disease where a small B-cell clone produces a monoclonal immunoglobulin light chain that causes deposits and specific organ dysfunction. The available treatment strategies aim to reduce or eliminate amyloidogenic light chain production in order to avoid amyloid deposition and allow the repair of organ damage. An international effort allowed the definition of validated hematologic and organ response criteria based on biomarkers. Recently, new methods for the assessment of minimal residual disease were also proposed but still need international validation. Lastly, a joint effort is also required to accurately define relapse/progression criteria in order to apply timely therapeutic interventions. In this review, we describe the validated response criteria and report on the future direction for the definition of progression criteria in this disease.

Highlights

Light chain (AL) amyloidosis is a disease where a small B-cell clone produces a monoclonal immunoglobulin light chain that causes deposits and specific organ dysfunction [1].Organ damage is known to be the result of the amyloid deposition itself or due to the direct cell toxicity of the circulating free light chains (FLC) [2]
The International Society of Amyloidosis (ISA) Board of Directors proposed that the 2012 response criteria should be expanded to define complete hematologic response as the absence of amyloidogenic light chains, which was defined as negative serum and urine immunofixation and either a FLC ratio within the reference range or an abnormal FLC ratio as long as the uninvolved-FLC concentration was greater than the involved-FLC concentration (Table 1) [14]
These are the only criteria reported and approved to date by the ISA but there is no consensus among the experts on the correct definition of relapse/progression routinely used in the clinic in order to start rescue therapy in a timely manner

Summary

Introduction

Light chain (AL) amyloidosis is a disease where a small B-cell clone produces a monoclonal immunoglobulin light chain that causes deposits and specific organ dysfunction [1]. The evaluation and monitoring of the hematologic and organ responses to each therapy line and at the time of relapse or progression are essential to adequately manage patients with this disease, both in daily clinical practice and in the setting of clinical trials [3] For this purpose, it is necessary to perform a complete diagnostic/staging work-up at diagnosis and before every line of therapy focused on establishing the baseline values of main indicators for the hematologic evaluation (serum FLC, serum and/or urine M-protein, and plasma cell infiltration) and for the organ assessment (24-h protein excretion, cardiac biomarkers, and alkaline phosphatase). We describe the validated response criteria and the future directions of hematologic and organ evaluation in this disease

Hematologic Response Assessment

Hematologic Response Assessment for Patients with Non-Measurable Disease

New Proposed Hematologic Response Criteria Based on FLC Measurement

Hematologic Response Based on New Tools for Assessment

Organ Response Assessment

Hematologic and Organ Progression Criteria

Monitoring Response Assessment during and off Treatment

Findings

Conclusions