Minimal residual disease in systemic light chain amyloidosis: a systematic review and meta-analysis.

PURPOSE: Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains controversial, and this systematic review and meta-analysis aims to fill this gap. METHODS: We searched for relevant studies on Pubmed, Embase, and Cochrane Controlled Register of Trials, nine studies involving 451 patients were included and meta-analyzed. This systematic review has been registered in PROSPERO (CRD42023494169). RESULTS: Our study found that in the group of patients who achieved very good partial response (VGPR) or better, MRD negativity was correlated with higher cardiac and renal response rates [pooled risk ratio (RR) = 0.74 (95% CI 0.62-0.89), 0.74 (95% CI 0.64-0.87), respectively]. Patients with MRD positivity had a higher hematologic progression rate within two years after MRD detection [pooled RR = 10.31 (95% CI 2.02-52.68)]; and a higher risk of hematologic + organ progression in the first year [pooled RR = 12.57 (95% CI 1.73-91.04)]. Moreover, MRD negativity was correlated with a better progression-free survival (PFS) [pooled hazard ratio (HR) = 0.27 (95% CI 0.17-0.45)]; but it did not significantly improve the overall survival (OS) [pooled HR = 0.34 (95% CI 0.11-1.07)]. CONCLUSION: In AL amyloidosis, our study supports that MRD negativity correlates with higher cardiac or renal response rates and indicates a better PFS in the follow-up. However, the correlation between OS and the status of MRD is not significant.

Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment.

DISEASE OVERVIEW: Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or MGUS." DIAGNOSIS: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy. PROGNOSIS: N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T(or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5-year survivals are 82%, 62%, 34%, and 20%, respectively. THERAPY: All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥VGPR. In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine. FUTURE CHALLENGES: Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to deplete deposited fibrils are underway.

Amyloid consults do not have to be vexing.

Diagnosing amyloidosis can be challenging due to its clinical heterogeneity, need for multiple specialists to make a diagnosis, and lack of a single diagnostic test for the disease. Patients are often diagnosed late, in advanced stage, and after exhibiting multiple symptoms and signs for a long period. It is important to develop a clinical suspicion of amyloidosis, particularly in those with multisystemic symptoms and high-risk patient populations such as those with precursor hematologic conditions. A systematic approach to the workup of suspected amyloidosis is key, including a comprehensive clinical assessment, laboratory tests to assess organ involvement, advanced imaging studies, screening for plasma cell disorder, and tissue biopsy when necessary. After making a diagnosis of amyloidosis, accurate typing of amyloid deposits, differentiating between localized and systemic amyloidosis, and appropriately staging the disease is important. Early diagnosis is crucial for improving patient outcomes and quality of life in light chain amyloidosis.

Clinical characterization and outcomes of a cohort of colombian patients with AL Amyloidosis.

Background: Amyloid light chain (AL) amyloidosis is characterized by amyloid fibril deposition derived from monoclonal immunoglobulin light chains, resulting in multiorgan dysfunction. Limited data exist on the clinical features of AL amyloidosis. Objective: This study aims to describe the clinical characteristics, treatments, and outcomes in Colombian patients with AL amyloidosis. Methods: A retrospective descriptive study was conducted at three high-complexity centers in Medellín, Colombia. Adults with AL amyloidosis diagnosed between 2012 and 2022 were included. Clinical, laboratory, histological, treatment, and survival data were analyzed. Results: The study included 63 patients. Renal involvement was most prevalent (66%), followed by cardiac involvement (61%). Multiorgan involvement occurred in 61% of patients. Amyloid deposition was most commonly detected in renal biopsy (40%). Bortezomib-based therapy was used in 68%, and 23.8% received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT-ASCT). Hematological response was observed in 95% of patients with available data. Cardiac and renal organ responses were 15% and 14%, respectively. Median overall survival was 45.1 months (95% CI: 22.2-63.8). In multivariate analysis, cardiac involvement was significantly associated with inferior overall survival (HR 3.27; 95% CI: 1.23-8.73; p=0.018), HDCT-ASCT had a non-significant trend towards improved overall survival (HR 0.25; 95% CI: 0.06-1.09; p=0.065). Conclusions: In this study of Colombian patients with AL amyloidosis, renal involvement was more frequent than cardiac involvement. Overall survival and multiorgan involvement were consistent with data from other regions of the world. Multivariate analysis identified cardiac involvement and HDCT-AHCT as possible prognostic factors.

Antecedentes: La amiloidosis por amiloide de cadenas ligeras (AL) se caracteriza por el depósito de fibrillas amiloides derivadas de cadenas ligeras de inmunoglobulinas monoclonales, lo que resulta en disfunción multiorgánica. Existen datos limitados sobre las características clínicas de la amiloidosis AL. Objetivo: Este estudio tiene como objetivo describir las características clínicas, tratamientos y desenlaces en pacientes colombianos con amiloidosis AL. Métodos: Se llevó a cabo un estudio descriptivo retrospectivo en tres centros de alta complejidad en Medellín, Colombia. Se incluyeron adultos con diagnóstico de amiloidosis AL entre 2012 y 2022. Se analizaron datos clínicos, de laboratorio, histológicos, de tratamiento y de supervivencia. Resultados: El estudio incluyó 63 pacientes. La afectación renal fue más prevalente (66%), seguida de la afectación cardíaca (61%). El 61% de los pacientes presentaron afectación multiorgánica. El depósito amiloide se detectó con mayor frecuencia en la biopsia renal (40%). El tratamiento basado en bortezomib se utilizó en el 68%, y el 23.8% recibió altas dosis de quimioterapia con trasplante autólogo de progenitores hematopoyéticos (ADQT-TAPH). Se observó respuesta hematológica en el 95% de los pacientes con datos disponibles. La respuesta de órgano cardíaca y renal fue del 15% y 14%, respectivamente. La mediana de la supervivencia global fue de 45.1 meses (IC del 95%: 22.2-63.8). En el análisis multivariado, la afectación cardíaca se asoció significativamente con una supervivencia global inferior (HR 3.27; IC del 95%: 1.23-8.73; p=0.018), ADQT-TAPH mostró una tendencia no significativa hacia una mejora en la supervivencia global (HR 0.25; IC 95%: 0.06-1.09; p=0.065). Conclusiones: En este estudio de pacientes colombianos con amiloidosis AL, la afectación renal fue más frecuente que la afectación cardíaca. La supervivencia global y la afectación multiorgánica fueron consistentes con datos de otras regiones del mundo. El análisis multivariado identificó la afectación cardíaca y ADQT-TAPH como posibles factores pronósticos.

The importance of pathways to facilitate early diagnosis and treatment of patients with cardiac amyloidosis.

Cardiac amyloidosis (CA) is a condition caused by extracellular deposition of amyloid fibrils in the heart. It is an underdiagnosed disease entity which can present with a variety of cardiac and non-cardiac manifestations. Diagnosis usually follows an initial suspicion based on clinical evaluation or imaging findings before confirmation with subsequent imaging (echocardiography, cardiac magnetic resonance imaging, 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy) in combination with biochemical screening for monoclonal dyscrasia (serum free light chains and serum and urine electrophoresis) and/or histology (bone marrow trephine, fat or endomyocardial biopsy). More than 95% of CA can be classified as either amyloid light-chain (AL) CA or amyloid transthyretin (ATTR) CA; these two conditions have very different management strategies. AL-CA, which may be associated with multiple myeloma, can be managed with chemotherapy agents, autologous stem cell transplantation, cardiac transplant and supportive therapies. For ATTR-CA, there is increasing importance in making an early diagnosis because of novel treatments in development, which have transformed this once incurable disease to a potentially treatable disease. Timely diagnosis is crucial as there may only be a small window of opportunity where patients can benefit from treatment beyond which therapies may be less effective. Reviewing the existing patient pathway provides a basis to better understand the complexities of real-world activities which may be important to help reduce missed opportunities related to diagnosis and treatment for patients with CA. With healthcare provider interest in improving the care of patients with CA, the development of an optimal care pathway for the condition may help reduce delays in diagnosis and treatment and thus enhance patient outcomes.

Autologous Stem Cell Transplant in Hodgkin's and Non-Hodgkin's Lymphoma, Multiple Myeloma, and AL Amyloidosis.

Human body cells are stem cell (SC) derivatives originating from bone marrow. Their special characteristics include their capacity to support the formation and self-repair of the cells. Cancer cells multiply uncontrollably and invade healthy tissues, making stem cell transplants a viable option for cancer patients undergoing high-dose chemotherapy (HDC). When chemotherapy is used at very high doses to eradicate all cancer cells from aggressive tumors, blood-forming cells and leukocytes are either completely or partially destroyed. Autologous stem cell transplantation (ASCT) is necessary for patients in those circumstances. The patients who undergo autologous transplants receive their own stem cells (SCs). The transplanted stem cells first come into contact with the bone marrow and then undergo engraftment, before differentiating into blood cells. ASCT is one of the most significant and innovative strategies for treating diseases. Here we focus on the treatment of Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, and AL amyloidosis, using ASCT. This review provides a comprehensive picture of the effectiveness and the safety of ASCT as a therapeutic approach for these diseases, based on the currently available evidence.

Cardiac and autologous stem cell transplantation hematopoietic in patients with AL amyloidosis.

OBJECTIVE: To describe the evolution of serum free light chains (FLC) in the period between orthotopic heart transplantation (OHT) and autologous stem cell transplantation (ASCT), the hematological response one year after ASCT and chemotherapy and immunosuppressive treatment in patients with AL amyloidosis. METHOD: Case series of consecutive patients diagnosed with AL amyloidosis who received OHT followed by ASCT from the Institutional Registry of Amyloidosis of the Italian Hospital of Buenos Aires, between January 2010 and November 2021. FLC values between transplants and at year post ASCT. Quantitative variables were described with their median and interquartile range. Categorical variables as absolute and relative frequencies. RESULTS: Of 106 patients with AL amyloidosis, 6 had an OHT followed by ASCT. The median age was 55 years. Most were men (n = 5). In the period between transplants, the involved CLL decreased in two patients and remained stable in three. All achieved complete hematologic remission 1 year after ASCT. A single patient presented relapse in the transplanted solid organ. Tacrolimus, mycophenolate mofetil, and corticosteroids were the immunosuppressive regimen used after OHT. CONCLUSIONS: OHT represents a treatment option in patients with severe heart failure due to amyloidosis, allowing later intensive treatment with induction chemotherapy and ASCT. Although studies are lacking, immunosuppressive therapy after OHT might have some effect on clonal plasma cells.

OBJETIVO: Describir la evolución de las cadenas livianas libres séricas (CLL) en el período comprendido entre el trasplante cardíaco ortotópico (TCO) y el trasplante de células progenitoras hematopoyéticas (TCPH), la respuesta hematológica al año tras el TCPH y el tratamiento quimioterápico e inmunosupresor en pacientes con amiloidosis AL. MÉTODO: Serie de casos de pacientes consecutivos con diagnóstico de amiloidosis AL que recibieron TCO seguido de TCPH del Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, entre enero de 2010 y noviembre de 2021. Se reportaron los valores de CLL entre trasplantes y al año del TCPH. Las variables cuantitativas se describieron como mediana e intervalo intercuartil, y las variables categóricas como frecuencias absolutas y relativas. RESULTADOS: De 106 pacientes con amiloidosis AL, seis tuvieron TCO seguido de TCPH. La mediana de edad fue de 55 años. La mayoría eran hombres (n = 5). En el período entre trasplantes, la CLL involucrada disminuyó en dos pacientes y se mantuvo estable en tres. Todos lograron la remisión hematológica completa al año del TCPH. Un solo paciente presentó recaída en el órgano sólido trasplantado. Tacrolimus, micofenolato de mofetilo y corticoides fue el esquema inmunosupresor utilizado después del TCO. CONCLUSIONES: El TCO representa una opción de tratamiento en pacientes con falla cardíaca grave por amiloidosis, permitiendo luego un tratamiento intensivo con quimioterapia de inducción y TCPH. Si bien faltan estudios, la terapia inmunosupresora después del TCO podría tener algún efecto sobre las células plasmáticas clonales.

Anti-B Cell Maturation Antigen Chimeric Antigen Receptor T Cell Therapy for the Treatment of AL Amyloidosis and Concurrent Relapsed/Refractory Multiple Myeloma: Preliminary Efficacy and Safety.

While immunotherapies, such as CAR T therapy and bi-specific antibodies, have revolutionized the treatment of multiple myeloma (MM), patients with AL amyloidosis have been excluded from trials with these agents due to concerns of underlying autonomic, cardiac, and renal dysfunction, leading to potentially fatal toxicities from these therapies. In this communication, we described the outcomes of two patients with AL amyloidosis and concurrent MM with underlying cardiac and/or renal dysfunction who underwent anti-BCMA CAR T cell therapy with ide-cel or cilta-cel, received cytokine release syndrome prophylaxis, and tolerated therapy well with manageable toxicities and achieved a MRD-negative state. We described the preliminary efficacy and safety of CAR T in patients with AL amyloidosis and highlighted the importance of patient selection and medical optimization of cardiac and renal function prior to CAR T.

How I Approach Light Chain Amyloidosis.

Immunoglobulin Light Chain Amyloidosis (AL) is a progressive disease which leads to organ dysfunction and death. Tremendous progress has been made in staging, response, and treatment. The key to better survival though is early diagnosis which can be difficult since the symptoms are often nonspecific and can be seen in more common conditions. Once the diagnosis is confirmed, staging systems are available to provide prognosis on overall and renal survival. There are a number of treatments now available that are effective and well-tolerated. Response criteria have also been developed for hematologic and renal response in order to maximize response and minimize adverse effects. Newer therapies are being developed in particular anti-fibril therapies that are in clinical trials. For those patients who had a very good partial response or better, kidney transplantation may be an option if the kidney failure is not reversed.

Nanobodies counteract the toxicity of an amyloidogenic light chain by stabilizing a partially open dimeric conformation.

Light chain amyloidosis (AL) is a systemic disease where fibrillar deposition of misfolded immunoglobulin light chains (LCs) severely affects organ function and results in poor prognosis for patients, especially when heart involvement is severe. Particularly relevant in this context is the cardiotoxicity exerted by still uncharacterized soluble LC species. Here, with the final goal of identifying alternative therapeutic strategies to tackle AL amyloidosis, we produced five llama-derived nanobodies (Nbs) specific against H3, a well-characterized amyloidogenic and cardiotoxic LC from an AL patient with severe cardiac involvement. We found that Nbs are specific and potent agents capable of abolishing H3 soluble toxicity in C. elegans in vivo model. Structural characterization of H3-Nb complexes revealed that the protective effect of Nbs is related to their ability to bind to the H3 VL domain and stabilise an unexpected partially open LC dimer in which the two VL domains no longer interact with each other. Thus, while identifying potent inhibitors of LC soluble toxicity, we also describe the first non-native structure of an amyloidogenic LC that may represent a crucial step in toxicity and aggregation mechanisms.

Safety and Efficacy of Propylene Glycol-Free Melphalan in Patients with AL Amyloidosis Undergoing Autologous Stem Cell Transplantation: Results of a Phase II Study.

Patients with systemic light chain (AL) amyloidosis undergoing treatment with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) may develop renal and cardiac toxicities potentially exacerbated by the co-solvent propylene glycol in conventional melphalan formulations. We investigated the safety and efficacy of propylene glycol-free melphalan (PGF-Mel) during HDM/SCT in patients with AL amyloidosis (ClinicalTrials.gov identifier NCT02994784). The primary objective of this phase II, open-label study was evaluation for renal dysfunction, new cardiac arrhythmias, and postural hypotension related to autonomic dysfunction. Secondary objectives included time to neutrophil and platelet engraftment, treatment-related mortality (TRM), overall hematologic response, organ response, and number of peritransplantation hospitalizations. Twenty-eight patients with AL amyloidosis enrolled, of whom 27 underwent HDM/SCT. PGF-Mel at 140 to 200 mg/m2 was administered i.v. in 2 equally divided doses. Patients were monitored for up to 30 days after the last administration of PGF-Mel to assess for treatment-related toxicity. Patients were followed for 12 months from the time of treatment with HDM/SCT for evaluation of hematologic and organ responses. Kaplan-Meier analysis was used to estimate progression-free survival. Two patients (7%) developed renal dysfunction, 5 (19%) experienced new cardiac arrhythmias, and 3 (11%) developed orthostatic hypotension. All patients achieved neutrophil and platelet engraftment, at a median of 10 days and 17 days post-HDM/SCT, respectively. TRM on day +100 was 0%. Peritransplantation hospitalization was required for 23 patients (85%). The most common nonhematologic adverse events were diarrhea (93%), fatigue (82%), and nausea (74%). At 6 months post-HDM/SCT, hematologic complete response or very good partial response occurred in 66% of the patients. At 12 months post-HDM/SCT, renal response occurred in 12 of 23 (52%) patients with renal involvement, and cardiac response occurred in 3 of 11 (27%) patients with evaluable cardiac involvement. Our data indicate that PGF-Mel is safe and efficacious as a high-dose conditioning regimen for autologous SCT in patients with AL amyloidosis.

Predictors of treatment response and survival outcomes in patients with advanced cardiac AL amyloidosis.

Patients with advanced cardiac immunoglobulin light chain (AL) amyloidosis have a poor prognosis. Early hematologic and cardiac responses can prolong survival, but predictors of these outcomes have yet to be clarified. We report on 142 patients with newly diagnosed stage IIIb AL amyloidosis. After a median follow-up of 60 months, the median overall survival (OS) was 9 months. Independent baseline factors associated with shorter OS were symptom onset to diagnosis >6 months (hazard ratio [HR], 1.94; P = .003); bone marrow plasmacytosis ≥ 10% (HR, 1.98; P = .01); troponin I > 0.635 ng/mL (HR, 1.62; P = .04); New York Heart Association class III or IV (HR, 1.67; P = .04); and 6-minute walk test distance < 200 m (HR, 1.85; P = .01). Early hematologic (within 1 month) and cardiac (within 3 months) responses were significantly associated with longer survival. In a 1-month landmark analysis, patients with a hematologic very good partial response, partial response, and no response had a median OS of 47, 25, and 5 months, respectively (P < .0001). Patients with cardiac response at 3 months had significantly longer OS (47 vs 11 months; P < .0001). On multivariable modeling, bortezomib use was associated with early hematologic and cardiac responses and longer OS. Symptom onset to diagnosis duration of >6 months and difference between the involved and uninvolved free light chain > 350 mg/L were independently associated with lower odds of an early cardiac response. This study identified factors predictive of treatment outcomes and survival in advanced cardiac AL amyloidosis.

Epidemiology and clinical outcomes of light-chain amyloidosis in Sweden: A nationwide population-based study.

OBJECTIVES: This study evaluated data from six Swedish national registries to fill current evidence gaps on the epidemiology, clinical burden, and overall survival (OS) associated with light-chain (AL) amyloidosis. METHODS: Patients newly diagnosed with AL amyloidosis were identified using six linked Swedish nationwide population-based registers. For each case, individuals from the general population were selected and matched with a maximum ratio of 1:5 based on age, sex, calendar year, and county. RESULTS: 846 patients newly diagnosed with AL amyloidosis and 4227 demographically matched individuals were identified. From 2011 to 2019, annual AL amyloidosis incidence increased from 10.5 to 15.1 cases per million. At baseline, patients with AL amyloidosis had a significantly higher disease burden including higher rates of cardiac and renal failure relative to the comparison group. Among patients with AL amyloidosis, 21.5% had incident heart failure and 17.1% had incident renal failure after initial diagnosis. Median OS for patients with AL amyloidosis was 56 months versus not reached in the matched general population comparison group. CONCLUSION: The incidence of newly diagnosed AL amyloidosis in Sweden increased over time with AL amyloidosis being associated with a higher risk of cardiac/renal failure and all-cause mortality compared with the general population.

Prognosis of light chain amyloidosis: a multivariable analysis for survival prediction in patients with cardiac involvement proven by endomyocardial biopsy.

BACKGROUND: Cardiac involvement is a main determinant of mortality in light chain (AL) amyloidosis but data on survival of patients with cardiac AL amyloidosis proven by endomyocardial biopsy (EMB) are sparse. METHODS: This study analysed clinical, laboratory, electrocardiography and echocardiographic parameters for their prognostic value in the assessment of patients with AL amyloidosis and cardiac involvement. Patients with AL amyloidosis who had their first visit to the amyloidosis centre at the University Hospital Heidelberg between 2006 and 2017 (n=1628) were filtered for cardiac involvement proven by EMB. In the final cohort, mortality-associated markers were analysed by univariate and multivariable Cox regression. Cut-off values for each parameter were calculated using the survival time. RESULTS: One-hundred and seventy-four patients could be identified. Median overall survival time was 1.5 years and median follow-up time was 5.2 years. At the end of the investigation period, 115 patients had died. In multivariable analysis, New York Heart Association-functional class >II (HR 1.65; 95% CI 1.09 to 2.50; p=0.019), left ventricular global longitudinal strain (HR 1.12; 95% CI 1.03 to 1.22; p=0.007), left ventricular end-systolic volume (HR 1.02; 95% CI 1.01 to 1.03; p=0.001), systolic pulmonary artery pressure (HR 0.98; 95% CI 0.96 to 0.99; p=0.027), N-terminal pro-B-type natriuretic peptide (HR 1.57; 95% CI 1.17 to 2.11; p=0.003) and difference in free light chains (HR 1.30; 95% CI 1.05 to 1.62; p=0.017) were independently predictive. CONCLUSION: Among all patients with AL amyloidosis those with cardiac involvement represent a high-risk population with limited therapy options. Therefore, accurate risk stratification is necessary to identify cardiac amyloidosis patients with favourable prognosis. Incorporation of modern imaging techniques into existing or newly developed scoring systems is a promising option that might enable the implementation of risk-adapted therapeutic strategies.

Role of individual factor X concentrate pharmacokinetic studies in perioperative management of AL amyloidosis-associated acquired factor X deficiency.

BACKGROUND: AL amyloidosis is associated with acquired factor X (FX) deficiency. Experience related to its management is limited to case reports and series using prothrombin complex concentrate, fresh frozen plasma, plasma exchange, recombinant activated factor seven, and desmopressin with limited and variable efficacy. FX concentrate has not been widely used in its management. STUDY DESIGN AND METHODS: We report our experience with the perioperative use of FX concentrate (Coagadex) in two patients with AL amyloidosis-associated acquired FX deficiency requiring surgery, using their individual pharmacokinetic studies to manage perioperative hemostasis. Pharmacokinetic studies involved obtaining post-infusion FX activity at 10 min, 2, and 4 h following the administration of FX concentrate to calculate the FX half-life. RESULTS: Both patients' plasma FX activity was successfully increased to provide perioperative hemostatic support. Monitoring FX activity post-surgery was also utilized to maintain FX activity levels to prevent post-operative bleeding. CONCLUSION: Pharmacokinetic studies have a useful role in tailoring preoperative FX repletion in patients with AL amyloidosis associated with acquired FX deficiency.

Differences in patient-reported outcomes (PROs) by disease severity in light chain (AL) amyloidosis.

OBJECTIVE: To assess the impact of organ involvement on patient-reported outcomes (PROs) in light chain (AL) amyloidosis. METHODS: PROs were evaluated using the KCCQ-12, PROMIS-29 + 2, and SF-36 in individuals with AL amyloidosis. The 2004 Mayo system was used to stage disease and cardiac, neurologic, and renal involvement was considered. Global physical and mental health (MH) scores, physical function (PF), fatigue, social function (SF), pain, sleep, and MH domains were evaluated. Effect sizes between scores were measured using Cohen's d. RESULTS: Of 297 respondents, the median age at diagnosis was 60 years with 58% cardiac, 58% renal, and 30% neurologic involvement. Fatigue, PF, SF, and global physical health with PROMIS and SF-36 discriminated the most by stage. Significant discrimination in PROMIS and/or SF-36 was seen in PF, fatigue, and global physical health with cardiac involvement. For neurologic involvement, PF, fatigue, SF, pain, sleep, global physical, and MH with PROMIS and role physical, vitality, pain, general health, and physical component summary with SF-36 were discriminatory. For renal amyloid, pain by SF-36 and PROMIS, and SF-36 MH and role emotional subscales were significant. CONCLUSIONS: Fatigue, PF, SF, and global physical health can discriminate stage, cardiac and neurologic, but not renal, AL amyloidosis involvement.

Is there a representative quality-of-life questionnaire for patients with AL amyloidosis?-systematic literature review.

Systemic AL amyloidosis is an incurable condition with various presentations and may cause multiple complications related to organ involvement. As survival has improved, disease and therapy-related quality of life (QoL) is becoming an increasingly important treatment endpoint. We review the literature summarising the utilised QoL questionnaires (QLQs) and assess their validity according to COSMIN (Consensus-based Standards for the Selection of Health Measurement Instruments) standards. Thirteen retrospective observational studies and thirty-two prospective clinical trials were analysed. Most QLQs are generic or only validated in populations with distinct complications of the disease. None meet 'strong evidence' for validation in this context. There is a need to develop a disease-specific QLQ, which could inform treatment choices and facilitate the approval of novel therapies.