Immunoglobulin Light Chain Amyloidosis Research Articles

Warning values of serum total kappa/lambda ratio for M-proteinemia

BackgroundTo introduce the serum total kappa/lambda ratio (K/L) in humoral immunity testing reports to improve the detection rate of M-proteinemia.Methods156 M protein-positive and 5464 M protein-negative samples confirmed by serum immunofixation electrophoresis(sIFE) were accumulated from January 2021 to December 2023 in the First Affiliated Hospital of Soochow University and the contents of immunoglobulins (IgG, IgA, IgM, kappa and lambda) were tested by Beckman IMMAGE800. All the samples were divided into two groups by time: the modeling group and the validation group. The K/L values in the modeling group were analyzed by SPSS 27.0 to get the receiver operating characteristic curve (ROC). Furthermore, a more in-depth analysis was conducted to verify the reliability of the optimal cutoff values in the validation group. In addition, the levels of immunoglobulins of another group including 106 patients with definite diagnosis of monoclonal gammopathy ranging from January 2021 to June 2024 were traced back to improve the diagnostic efficiency.ResultsThe optimal cutoff values of K/L were 2.31 and 1.43 corresponding to K-type and L-type M-proteinemia respectively by ROC analysis. The sensitivity and specificity were validated as 76.14% and 77.42%. False positives were mainly found in samples with systemic sclerosis (36.84%), hypohepatia (28.71%) and sicca syndrome (27.27%). While false negatives were mainly found in IgA monoclonal gammopathy (38.39%) and IgM monoclonal gammopathy (28.57%). Combining with the detection rules of IgG, IgA and IgM, the sensitivities for the diagnosis of immunoglobulin light chain amyloidosis(AL) and monoclonal gammopathy of undetermined significance(MGUS) can be increased to 83.33% and 85%.ConclusionsK/L > 2.31 and K/L < 1.43 can be used as warning values for M-proteinemia. In addition, the content of the heavy chain in IgA- or IgM-type M-proteinemia may be considered to improve the detection rate.

Conformational Differences in the Light Chain Constant Domain of Immunoglobulin G and Free Light Chain May Influence Proteolysis in AL Amyloidosis

Immunoglobulin light chain amyloidosis (AL) is a life-threatening disease caused by the deposition of light chain (LC) and its fragments containing variable (VL) and portions of constant (CL) domains. AL patients feature either monoclonal free LCs (FLCs) circulating as covalent and noncovalent homodimers, or monoclonal immunoglobulin (Ig) wherein the LC and heavy chain (HC) form disulfide-linked heterodimers, or both. The role of full-length Ig in AL amyloidosis is unclear as prior studies focused on FLC or VL domain. We used a mammalian cell-based expression system to generate four AL patient-derived full-length IgGs, two non-AL IgG controls, and six corresponding FLC proteins derived from an IGLV6-57 germline precursor. Comparison of proteins’ secondary structure, thermal stability, proteolytic susceptibility, and disulfide link reduction suggested the importance of local vs. global conformational stability. Analysis of IgGs vs. corresponding FLCs using hydrogen–deuterium exchange mass spectrometry revealed major differences in the local conformation/dynamics of the CL domain. In all IgGs vs. FLCs, segments containing β-strand and α-helix βAC-αACBC were more dynamic/exposed while segment βDC-βEC was less dynamic/exposed. Notably, these segments overlapped proteolysis-prone regions whose in vivo cleavage generates LC fragments found in AL deposits. Altogether, the results suggest that preferential cleavage in segments βAC-αACBC of FLC or βDC-βEC of LC in IgG helps generate amyloid protein precursors. We propose that protecting these segments using small-molecule stabilizers, which bind to the interfacial cavities CL-CL in FLC and/or CL-CH1 in IgG, is a potential therapeutic strategy to complement current approaches targeting VL-VL or VL-CL stabilization of LC dimer.

Light-chain amyloidosis with dysphagia as the main symptom: a case report

BackgroundImmunoglobulin light-chain amyloidosis is a relatively rare condition with a worldwide incidence of 5.1–12.8 cases per million person-years (Baker, 2022). It is characterized by a clonal population of immunoglobulin-secreting cells that produce a monoclonal light chain of κ or λ type as either an intact molecule or a fragment.Case presentationA 69-year-old East Asian (Chinese) male patient who presented with progressive dysphagia visited multiple hospitals repeatedly for more than 2 years and was finally diagnosed with immunoglobulin light-chain amyloidosis.ConclusionsOtolaryngologists should consider immunoglobulin light-chain amyloidosis when encountering suspicious clinical manifestations and intervene early to avoid misdiagnosis.

Machine-learning based subgroups of AL amyloidosis and cumulative incidence of mortality and end stage kidney disease.

Immunoglobulin light chain (AL) amyloidosis is a multisystem disease with varied treatment options and disease-related outcomes. Current staging systems rely on a limited number of cardiac, renal, and plasma cell dyscrasia biomarkers. To improve prognostication for all-cause mortality and end-stage kidney disease (ESKD), we applied unsupervised machine learning using a comprehensive set of clinical and laboratory parameters. Our study cohort comprised 2067 patients with newly diagnosed, biopsy-proven AL amyloidosis from the Boston University Amyloidosis Center. Variables included 31 clinical symptoms and 28 baseline laboratory values. Our clustering algorithm identified three subgroups of AL amyloidosis (low-risk, intermediate-risk, and high-risk) with distinct clinical phenotypes and median overall survival (OS) estimates of 6.1, 3.7, and 1.2 years, respectively. The 10-year adjusted cumulative incidences of all-cause mortality were 66.8% (95% CI 63.4-70.1), 75.4% (95% CI 72.1-78.6), and 90.6% (95% CI 87.4-93.3) for low, intermediate, and high-risk subgroups. The 10-year adjusted cumulative incidences of end-stage kidney disease (ESKD) were 20.4% (95% CI 6.1-24.5), 37.6% (95% CI 31.8-43.8), and 6.7% (95% CI 2.8-11.3) for low-risk, intermediate-risk, and high-risk subgroups. Finally, we trained a classifier for external validation with high cross-validation accuracy (85% [95% CI 83-86]) using a subset of easily obtainable clinical parameters. This marks an initial stride toward integrating precision medicine into risk stratification of AL amyloidosis for both all-cause mortality and ESKD.

Biochemical profile of renal amyloidosis in a Latin American cohort.

Two-thirds of patients with immunoglobulin light chain (AL) amyloidosis have renal involvement. The biochemical profile of kidney damage is poorly described. A cross-sectional study was conducted involving patients diagnosed with AL amyloidosis and renal involvement between January 1, 2010, and April 30, 2022 at the Hospital Italiano de Buenos Aires. Participants were retrospectively identified from the Institutional Amyloidosis Registry. Patients diagnosed with AL amyloidosis and evidence of renal involvement were included. Individuals with other types of amyloidosis were excluded. The selection process involved a thorough review of medical records and registry data to ensure accurate identification and inclusion of eligible participants. Seventy-seven patients were included. At diagnosis, 90% of the subjects had proteinuria, with a median of 4.3g/24h, 61% had renal failure, and 47% presented nephrotic syndrome. Semi-automated urinary electrophoresis revealed 55% with non-selective and 21% with moderately selective glomerular proteinuria. Urine immunofixation indicated 64% with lambda monoclonal free light chains and 12% with kappa. Serum immunofixation demonstrated 48% with lambda monoclonal type and 25% with lambda IgG.At the time of diagnosis of AL amyloidosis, the median age was 66years (IQR 53-72) and 49% were men. In addition to kidney involvement, other organs were also affected: heart in 53%, gastrointestinal system in 19%, peripheral nervous system in 16%, and liver in 16% of patients. Our study provides a biochemical profile in renal amyloidosis due to immunoglobulin light chains in a Latin American population. Proteinuria emerged as the most commonfinding in this cohort with frequent multiorgan involvement.

Dexamethasone for the Treatment of Cardiac Al Amyloidosis: A Case Report and Literature Review

Background: Systemic immunoglobulin light chain (AL) amyloidosis is a condition characterised by the conversion of light chains (LCs) from their soluble states into highly organised fibrillar aggregates that deposit in tissues, resulting in progressive organ damage and dysfunction. While previously considered incurable, treatment strategies are emerging for cardiac amyloidosis, underscoring the importance of early diagnosis. Case Summary: We present the case of a 69-year-old male patient who was admitted with acute onset of dyspnea and diagnosed with heart failure. The diagnosis of cardiac amyloidosis was made on the basis of a discrepancy between the results of the electrocardiogram and the echocardiogram, a conclusion that was further substantiated by the use of scintigraphy and myelogram. Given the poor left ventricular fraction, the standard chemotherapy regimen was replaced with corticosteroid therapy, which led to a significant improvement within the first 48 hours, unfortunately reversible with rapid clinical deterioration followed by sudden death within a week. Conclusion: Our aim is to highlight that early administration of dexamethasone is associated with significant clinical improvement but a high mortality rate in patients with AL cardiac amyloidosis.

Diagnostic performance of liver stiffness as marker of liver involvement in systemic immunoglobulin light chain (AL) amyloidosis.

To investigate the diagnostic performance of liver stiffness for detecting liver involvement in immunoglobulin light chain (AL) amyloidosis. Liver stiffness was measured using transient elastography in 71 patients with systemic AL amyloidosis and 18 patients with wild type transthyretin (ATTRwt) amyloidosis with cardiomyopathy. Both non-invasive consensus criteria and serum amyloid P component (SAP) scintigraphy were used as substitute standards instead of liver biopsy for establishing liver involvement. Liver stiffness was higher in AL amyloidosis patients with liver involvement than in those without: this was observed using both consensus criteria (median 14.4kPa vs. 8.1kPa; p = 0.001) and SAP scintigraphy (median 20.9kPa vs. 6.2kPa; p < 0.001). Liver stiffness was also higher in AL amyloidosis patients with liver involvement compared to AL and ATTRwt amyloidosis patients with cardiac involvement. Based on receiver operating characteristic (ROC) curves a cut-off value of 14.4kPa for stiffness was optimal to indicate liver involvement, providing sensitivity and specificity of 50% and 74%, respectively, using the consensus criteria and 63% and 90%, respectively, using SAP scintigraphy as standard. Liver stiffness is a promising tool to establish liver involvement in AL amyloidosis having potential to become part of updated criteria for liver involvement.

Enhancing prognostic guidance in renal light-chain amyloidosis: a new staging system incorporating pathological characters.

Advancements in treatment regimens have led to improved outcomes in renal Immunoglobulin light-chain amyloidosis. Nevertheless, a subset of patients may still experience renal adverse events despite achieving hematologic very good partial response or better. This discrepancy may be attributed to the deposition pattern of amyloid in renal tissue. To enhance prognostic assessment, a staging system that incorporates both pathological characteristics and clinical indicators should be developed. Patients newly diagnosed through renal biopsy between January 1, 2017, and December 31, 2022, were included. The renal pathology of patients was evaluated according to amyloid score (AS). Risk factors for end-stage renal disease or renal progression were identified by thecompeting risk model, then to develop a renal staging system. The Concordance index (C-index), internal cross-validation and Decision Curve Analysis (DCA) were used to evaluate the performance of the new staging system. 74 patients were included, and 16 (21.6%) patients had end-stage renal disease or renal progression within 24.7 (11.9, 50.7) months. AS and estimated glomerular filtration rate (eGFR) were identified as independent risk factors and the staging system based on them, which the C-index was 0.81 (95%CI, 0.73-0.89), had greater improvement than previous staging systems. The internal cross-validation and DCA also confirmed its great clinical benefits. The AS demonstrated its prognostic significance in Chinese patients, and the novel renal staging system based on AS and eGFR may provide great prognostic guidance for these patients.

Prognostic factors in Chinese patients with immunoglobulin light chain amyloidosis: a scoping review and meta-analysis

Objective This scoping review and meta-analysis aimed to map the evidence regarding prognostic factors in Chinese patients with immunoglobulin light chain (AL) amyloidosis and to identify current research gaps. Methods We searched EMBASE, PubMed, and CNKI databases from their inception to 15 September 2021. All studies investigated the association between any prognostic factor and target outcomes, including overall survival (OS), progression-free survival (PFS), and end-stage renal disease (ESRD) in Chinese patients with AL amyloidosis. Results This scoping review included 52 studies, of which 44 with 6,432 patients contributed to the multivariate prognostic analysis. Multivariate analysis identified a total of 106 factors that correlated with OS, 16 factors with PFS, and 18 factors with ESRD. Five prognostic factors were significantly associated with PFS, and 11 prognostic factors were significantly associated with ESRD. Meta-analysis was only available for prognostic factors without heterogeneous cutoff values, for which hazard ratios (HRs) and their 95% confidence intervals (CIs) were reported. Meta-analysis showed that bone marrow plasma cells (BMCs) (HR: 1.96, 95% CI: 1.21–3.19, p < 0.05) and interventricular septal thickness (IVST) (HR: 1.23, 95% CI: 1.10–1.38, p < 0.05) were independently associated with OS. Conclusion The significant prognostic factors associated with OS, PFS, and ESRD in Chinese patients with AL amyloidosis were related to plasma cell tumor load, biological characteristics, cardiac involvement, renal involvement, population characteristics, and treatment. Further studies should explore additional prognostic factors in patients with AL amyloidosis to develop prognostic models.

Advancing precision medicine in immunoglobulin light-chain amyloidosis: a novel prognostic model incorporating multi-organ indicators.

To develop a more accurate prognostic model that incorporates indicators of multi-organ involvement for immunoglobulin light-chain (AL) Amyloidosis patients. Biopsy-proven AL amyloidosis patients between January 1, 2012, and February 28, 2023, were enrolled and randomly divided into a training set and a test set at a ratio of 7:3. Prognostic indicators that comprehensively cover cardiac, renal, and hepatic involvement were identified in the training set by random survival forest (RSF). Then, RSF and Cox models were established. The Concordance index (C-index) and integrated brier scores (IBS) were applied to evaluate the models' performance in the test set. Besides, the net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated. A total of 173 eligible patients were included. After a median follow-up of 25.9 (9.2, 50.3) months, 48 (27.7%) patients died. Creatine kinase-MB, estimated glomerular filtration rate ≤ 50mL/min/1.73m2, interventricular septum ≥ 15mm, ejection fraction, alanine aminotransferase and Live involved were selected to develop prediction models. The RSF model based on the above indicators achieved C-index and IBS values of 0.834 (95% CI 0.725-0.915) and 0.151 (95% CI 0.1402-0.181), respectively. At last, the NRI and IDI of the RSF model were 0.301 (95% CI 0.048-0.546, P = 0.012) and 0.157 (95% CI 0.041-0.269, P < 0.001) at 5-year by comparing the RSF model with the Cox model which is based on the Mayo 2012 staging system. The RSF model that incorporates indicators of multi-organ involvement had a great performance, which may be helpful for physicians' decision-making and more accurate overall survival prediction.

Delayed identification of monoclonal protein is associated with early death in isolated cardiac AL amyloidosis

Background Early identification of immunoglobulin light-chain amyloidosis (AL) is crucial due to its rapid progression. Monoclonal light-chain (M-LC) testing is the first step in the diagnostic workup for patients with suspected cardiac amyloidosis (CA). We aimed to determine whether the time interval between the first CA suspicion and M-LC testing can be related to AL amyloidosis survival outcomes. Methods All patients (n = 94) with isolated cardiac AL amyloidosis diagnosed at our center between 2016 and 2020 were included. Those with pre-existing known monoclonal protein (monoclonal gammopathy of undetermined significance or smoldering multiple myeloma) were excluded. Time intervals to diagnostic tests and diagnosis were calculated and assessed for their survival prediction ability. Results The time interval between first CA suspicion (on echocardiography) and M-LC testing correlated with early mortality, and the best cutoff predicting survival, was 6 weeks. The 26 patients (∼28% of entire cohort) who underwent M-LC-studies >6 weeks after first suspicion more frequently presented Mayo stage IIIb (65% vs. 35%, p = .008), showing poorer overall survival than those (n = 68, 72%) referred for early M-LC studies (median 3 vs. 14 months, p = .039). Conclusions Monoclonal protein testing should be the first-step in the diagnostic workup for patients with echocardiographic/other instrumental red flags raising CA suspicion.

A patient with pulmonary hypertension: a rare case of AL amyloidosis involving the heart and external auditory canal

The article presents a case of immunoglobulin light chain amyloidosis with cardiac involvement without typical noncardiac manifestations. A complex diagnostic search for the cause of newly diagnosed pulmonary hypertension is described. Aspects of differential diagnosis in invasive hemodynamic assessment of pulmonary circulation and echocardiographic data are discussed. A special case feature is involvement of the hearing organ, which is very rare.

Options for Rescue Treatment of Patients with AL Amyloidosis Exposed to Upfront Daratumumab.

This review aims to assess the therapeutic strategies available for relapsed/refractory patients with immunoglobulin light chain (AL) amyloidosis who received upfront daratumumab-based regimens. The treatment landscape of AL amyloidosis has changed radically thanks to the introduction in the upfront setting of daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone (DaraCyBorD) which improved patients' outcomes increasing the rate of hematologic and organ responses. However, many patients eventually relapse or are refractory to daratumumab and the best salvage therapy is not well defined yet. In this contest, we reviewed the available therapeutic options after daratumumab failure, and we look towards the current advances in Bcl-2 inhibitors, novel immunotherapeutic agents as chimeric antigen receptor (CAR-T) therapy and bispecific antibodies (bsAbs). Relapsed/refractory AL amyloidosis represent an unmet clinical need and novel targeted drugs require urgent prospective assessment.

Kidney Amyloidosis: Updates on Pathogenesis and Therapeutic Frontiers.

Amyloidosis includes a diverse group of rare diseases characterized by the misfolding of native or mutant proteins, leading to extracellular accumulation in various organs. While 42 proteins have been identified to date, their distribution differs between systemic and localized forms. Mass spectrometry analysis of tissue samples in the USA shows immunoglobulin light chain (AL) amyloidosis as the most prevalent systemic type, followed by transthyretin (ATTR). Heart and kidney involvements are common. Although there are 14 recognized types of kidney-related amyloidosis, clinicopathologic studies in the USA have identified 11 types, with AL amyloidosis being the most prevalent cause of kidney involvement. This review focuses on AL, AA, and ATTR amyloidosis due to their common systemic presentations. Recent US-based clinicopathologic studies challenge conventional beliefs that toxicity is primarily driven by amyloid deposition and highlight the role of the complement pathway. Diagnostic methods, particularly mass spectrometry, are crucial for accurate typing. Treatment strategies vary depending on the underlying type, with AL amyloidosis primarily targeting plasma cell clones, AA amyloidosis addressing underlying inflammation with systemic therapies, and ATTR amyloidosis focusing on ATTR stabilization or gene silencing.

Intraoral hemorrhagic bullae as the first sign of immunoglobulin light chain amyloidosis.

Intraoral hemorrhagic bullae as the first sign of immunoglobulin light chain amyloidosis.

Serum monoclonal immunoglobulin light-chain detection differs between immunofixation electrophoresis methods in patients with AL amyloidosis.

Serum immunofixation electrophoresis (IFE) is often performed for screening monoclonal proteins (M proteins) in immunoglobulin light-chain amyloidosis (AL amyloidosis). However, the performance of serum IFE for detecting M protein in AL amyloidosis patients is often insufficient. In this study, we examined the detection rate of serum M protein in newly diagnosed AL amyloidosis patients and analyzed differences in M protein detection between IFE methods. Among 60 patients newly diagnosed with AL amyloidosis, 22 had undetectable serum M protein by IFE with the Epalyzer2 system. Samples with undetectable M protein had significantly lower involved serum-free light-chain (iFLC) and a smaller difference between involved and uninvolved serum-free light-chain (dFLC) values than samples with IFE-detectable monoclonal light chains. When samples that tested negative for M protein by the Epalyzer2 system were retested by IFE with the HYDRASYS 2 system, 50% had IFE-detectable monoclonal light chains. The IFE system and reagents used may affect serum monoclonal immunoglobulin light-chain detection in AL amyloidosis patients, especially those with low iFLC or low dFLC samples. More attention should be paid to the performance of IFE systems, since it may affect the diagnostic and therapeutic evaluation of AL amyloidosis patients.

The Real-World Data on Patients With Cardiac Stage IIIb AL Amyloidosis

BackgroundMorbidity and mortality of patients with immunoglobulin light chain (AL) amyloidosis are strongly associated with the severity of cardiac involvement, especial in patients with cardiac stage IIIb, but the real-world data on these patients is still limited. Patients and MethodsA retrospective analysis was conducted on 77 patients diagnosed with cardiac stage IIIb AL amyloidosis at our center. We analyzed the clinical characteristics, treatment and outcome of the patients. ResultsThe median age of patients was 57 years and 49.4% were male. Median serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were 13,384 ng/L and 0.166 ug/L, and 42 (54.5%) patients had heart failure at diagnosis. Fifty-seven (74.0%) patients received antiplasma cell treatment, and the main treatment options include bortezomib or thalidomide combined with dexamethasone. The hematologic overall response rate was 70% (28/40), and at 6-month landmark analysis, patients with hematologic responses had a higher survival rate. Cardiac and renal responses were achieved in 14 (37.8%) and 13 (32.5%) patients, respectively. After a median follow-up of 10 months (range 1-115 months), median overall survival (OS) was 18 months, and the estimated survival rates at 3, 6, and 12 months were 79.9%, 75.6%, and 54.5%, respectively. In Cox regression models, age, hypotension and cTnT were independently predictive of mortality after adjusting for heart failure. ConclusionThe hematologic, cardiac and renal responses were relative lower in patients with cardiac stage IIIb AL amyloidosis. The overall prognosis of patients was poor, and age, hypotension, and cTnT can be used to predict mortality.

Primary Data on ATTR-Amyloidosis Prevalence Among Elderly Patients With Left Ventricular Hypertrophy in Russia.

To estimate the prevalence of amyloid cardiomyopathy (CM) caused by transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) amyloidosis among patients aged &gt;65 years with interventricular septal (IVS) hypertrophy of ≥14 mm. From January through August 2023, 60 patients (mean age 7.2±7.3 years, 34 (56.67%) men) were enrolled. Patients meeting the inclusion criteria underwent an echocardiographic study with determining the myocardial longitudinal strain, myocardial scintigraphy with 99mTc-pyrfotech, myocardial single-photon emission computed tomography, measurement of N-terminal fragment of brain natriuretic peptide and troponin I, and the immunochemical study of serum and urine proteins with measurement of free light chains. In the presence of grades 2 and 3 radiopharmaceutical uptake according to scintigraphy, a molecular genetic study was performed for differential diagnosis of wild-type transthyretin amyloidosis (wtATTR) and hereditary/variant (hATTR) ATTR-CM. According to data of myocardial scintigraphy with 99mTc-pyrfotech, grade 3 uptake in the absence of monoclonal secretion was detected in 5 (8.3%) cases and grade 2 radiotracer uptake in the absence of monoclonal secretion was detected in 6 (10%) patients. Myeloma complicated by AL amyloidosis and primary AL amyloidosis were found in 5 (8.3%) patients. Among patients aged ≥65 years with IVS hypertrophy ≥14 mm, amyloid CM was detected in 20% of cases (12 patients), including 5 cases (8.3%) of AL amyloidosis and 7 cases (11.7%) of ATTR amyloidosis.

Oxidative damage in immunoglobulin light chain and transthyretin cardiac amyloidosis – a closer look

Heart failure is a progressive disease, representing a growing cause of morbidity, hospitalization, and mortality. An increasingly common type of heart failure with preserved ejection fraction (HFpEF) is an immunoglobulin light chain and transthyretin cardiac amyloidosis, in the pathophysiology of which oxidative damage appears to exert a strong impact. Reactive oxygen and nitrogen species have physiological signaling functions, but their overaccumulation, as in cardiac amyloidosis, leads to cardiomyocyte damage and apoptosis, and to cardiac hypertrophy and fibrosis. Moreover, such pathological processes worsen the redox damage with the perpetuation of an inflammatory state, in a vicious cycle. Here, the role of oxidative damage in the transthyretin and immunoglobulin light chain cardiac amyloidosis, the underlying pathogenic mechanisms, the therapeutic implications, and possible future strategies are reviewed.

Clonal hematopoiesis of indeterminate potential in patients with immunoglobulin light-chain AL amyloidosis

AbstractImmunoglobulin light-chain (AL) amyloidosis is characterized by the deposition of misfolded monoclonal free light chains, with cardiac complications accounting for patient mortality. Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with worse cardiovascular outcomes in the general population. Its significance in AL amyloidosis remains unclear. We collected clinical information and outcome data on 76 patients with a diagnosis of AL amyloidosis who underwent deep targeted sequencing for myeloid neoplasia–associated mutations between April 2018 and August 2023. Variant allele frequency was set at 2% to call CHIP-associated mutations. CHIP mutations were present in patients with AL amyloidosis at a higher frequency compared with age-matched control individuals. Sixteen patients (21%) had at least 1 CHIP mutation. DNMT3A was the most frequent mutation (7/16; 44%). Compared with patients without CHIP, patients with CHIP had a higher prevalence of t(11;14) translocation (69% vs 25%, respectively; P = .004). Furthermore, among patients with renal involvement, those with CHIP had a lower Palladini renal stage (P = .001). At a median follow-up of 32.5 months, the presence of CHIP was not associated with worse overall survival or major organ dysfunction progression-free survival. Larger studies and longer follow-up are needed to better define the impact of CHIP in patients with AL amyloidosis.