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

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.

Response rates to second‐line treatment with daratumumab bortezomib dexamethasone (DVD) in relapsed/refractory light chain amyloidosis (AL) after initial Bortezomib‐based regime

“…One significant challenge remains in the lack of global consensus on what is considered an inadequate response, limitations of the ISA criteria defining relapse, and lack of consensus as to when to start second-line treatments. 16,22,32 Hence, the decision for treatment was taken in a multidisciplinary meeting at the UK-NAC and was based on a combination of haematological response, organ involvement, organ response, clinical phenotype and fitness for therapy.…”

“…There are no consensus guidelines defining the optimal time to start second‐line therapy following biochemical relapse; however, delaying treatment till organ progression results in poorer outocmes 22 . Patients who demonstrate a clear progression of iFLC, although not fulfilling specific relapse criteria, were considered for second‐line therapy treatment based upon consensus opinion accounting for disease severity, organ involvement and other patient/disease‐dependent factors.…”

“…We acknowledge the limitation of this series of patients with heterogeneous drug dosing, limited adverse event reporting (hence not discussed in this paper) and lack of bone marrow biopsy results at both diagnosis and relapse including fluorescent in‐situ hybridisation (FISH) results. One significant challenge remains in the lack of global consensus on what is considered an inadequate response, limitations of the ISA criteria defining relapse, and lack of consensus as to when to start second‐line treatments 16,22,32 . Hence, the decision for treatment was taken in a multidisciplinary meeting at the UK‐NAC and was based on a combination of haematological response, organ involvement, organ response, clinical phenotype and fitness for therapy.…”

Light-Chain Amyloidosis: The Great Impostor

“…Since AL is caused by light-chain immunoglobulins, the difference between involved and uninvolved free light chains (dFLCs) has evolved as the method of choice to evaluate clonal disease response, since it provides more accurate assessment compared to the ratio of the free light chains. Four (4) hematological response categories have been defined [50]:…”

“…In the last two years, the FDA has approved two CAR-T products targeting BCMA for patients with refractory MM after three lines of treatment [50,61]. Reports on the use of these products in AL patients have been scarce in the literature.…”