September 2026 Research Update

Across this set of papers, diagnosis was shown as a stepwise process that often relies on finding amyloid in tissue and then using organ-focused testing to understand where amyloid is affecting the body. Larger pooled evidence suggested that sampling abdominal fat can detect amyloid in many people with AL amyloidosis, while bone marrow testing alone misses more cases. Smaller studies and case reports highlighted additional sampling sites (salivary gland, lymph node, heart) and imaging-based approaches aimed at identifying heart or liver involvement. [1] [2] [3] [4] [5] [6]

In a systematic review and meta-analysis that used organ biopsy as the reference, abdominal fat pad sampling had a pooled sensitivity of 0.77, while bone marrow biopsy had a pooled sensitivity of 0.55. In one included study, using both tests together increased sensitivity to 0.89, suggesting that combining sampling sites can reduce missed diagnoses, although specificity was not reported. [1]

Several single-patient reports showed that amyloid can also be found through biopsies from other sites when clinical clues point there. One person with suspected cardiac amyloidosis was diagnosed through a small salivary gland biopsy from the lip, using Congo red staining and confirmation of AL type at a national center. Another report described amyloid detected in a lymph node sample using fine-needle aspiration with Congo red staining in a woman who also had marginal zone lymphoma. [2] [3]

For suspected heart involvement, one prospective single-center study tested an amyloid-targeting PET/CT scan in newly diagnosed, untreated AL amyloidosis. In 25 people considered to have cardiac involvement by consensus criteria, early-to-late images showed uptake in all 25 (reported sensitivity 100%), while delayed uptake was absent in 4 of 25, showing that timing of imaging can matter. A separate case report illustrated how combining heart imaging with blood testing for abnormal proteins led to confirmation by heart biopsy in an asymptomatic man evaluated for inherited heart thickening. [5] [4]

For possible liver involvement, a study that included a retrospective multicenter group and a smaller prospective follow-up group reported that a liver stiffness measurement cutoff of 13.6 kPa had 92% sensitivity and 71% specificity for hepatic involvement, with larger values seen in people categorized as having liver involvement. In the prospective portion, liver stiffness sometimes fell over time, and the authors suggested that large decreases might reflect liver improvement, but they noted that thresholds need validation in larger studies. [6]

A separate international expert consensus focused on rare muscle problems linked to abnormal blood proteins, including AL amyloid myopathy. The group recommended Congo red staining on muscle biopsies to check for amyloid when evaluating these muscle conditions, highlighting that biopsy testing can be tailored to the organ or symptom being investigated. [7]

One case report described how consumer wearable data (frequent resting fast heart rate alerts) prompted evaluation that ultimately confirmed AL amyloidosis by heart biopsy, showing how symptoms and monitoring data can sometimes serve as an early clue that leads to formal diagnostic testing. Because this was one patient, it does not show how often wearables help, but it illustrates one path to diagnosis. [8]

For patients and caregivers, these papers mainly reinforce that AL amyloidosis diagnosis often depends on demonstrating amyloid in tissue and then using additional tests to understand organ involvement, especially the heart and liver. The strongest evidence in this set comes from pooled data on fat pad sampling and bone marrow biopsy, while the heart PET/CT and liver stiffness results are early and based on smaller cohorts, so how well they work across many centers is still uncertain. The case reports are useful for showing real-world routes to diagnosis (salivary gland, lymph node, early heart disease, or wearable-triggered workup), but they cannot predict what will happen for most people.

Across these papers, a consistent message was that amyloid type can be misidentified when testing relies too heavily on a single scan or on incomplete typing. Several real-world cases showed that rare amyloid proteins can look like more common forms, and that mass spectrometry on biopsy tissue can provide the most definitive answer when results do not match the overall clinical picture. [9] [10] [11]

In a three-patient cardiac case series, one person had a false-positive screening heart scan that initially suggested transthyretin (ATTR) amyloid in the heart, but a more detailed scan view did not confirm uptake in the heart muscle and the diagnosis was revised away from amyloidosis. The same series included a patient whose immunoglobulin light-chain (AL) amyloidosis diagnosis was delayed until Congo red testing and mass spectrometry-based typing on tissue, after which the person was already very ill from advanced disease. [9]

Two reports highlighted apolipoprotein A-IV (ApoA-IV) as a less common cause of cardiac amyloid that may be missed or confused with other types using routine noninvasive testing. In one patient, both a bone-based heart scan and blood and urine testing for abnormal proteins were negative, yet heart biopsy with mass spectrometry identified ApoA-IV as the amyloid protein. [10]

In a two-patient series, one person had negative noninvasive testing but biopsy still showed ApoA-IV cardiac amyloid, while another had blood test results that looked like AL amyloidosis, yet mass spectrometry typing of heart tissue identified ApoA-IV instead and chemotherapy was stopped. These cases illustrate how discordant blood tests, scans, and symptoms can occur, and why definitive amyloid typing matters before labeling someone with AL or ATTR. [11]

A separate laboratory-style methods paper (based on matched urine and kidney samples) described an advanced mass spectrometry workflow that reconstructed eight urine light-chain sequences and matched each to the corresponding kidney amyloid deposits, with high coverage of the variable region. While not a clinical outcomes study, it supports the broader theme that detailed protein-level approaches can strengthen confidence in amyloid typing in difficult cases. [12]

Finally, a systematic review of 41 phase III multiple myeloma drug trials found that trials often excluded amyloidosis but did not actively screen for it, and they rarely reported detailed baseline heart testing or used consistent definitions for heart-related side effects. This suggests that amyloidosis and heart involvement may be inconsistently identified or described in myeloma trials, which can make it harder to interpret how well trial results apply to people who have both conditions. [13]

For patients and caregivers, this group of papers mainly serves as background on why accurate amyloid typing can be complicated, especially when the heart is involved or when rare amyloid proteins are present. The reports emphasize that scans and blood and urine tests can sometimes be misleading in either direction (false positives or false negatives), and that mass spectrometry-based typing of biopsy tissue is often treated as the clearest way to identify the amyloid protein when results conflict. What remains uncertain is how often these specific pitfalls happen in broader patient populations, because several of the papers were small case reports or small case series.

This month, treatment studies in AL amyloidosis mainly focused on antibody-based approaches: one antibody aimed at the abnormal plasma cells making the amyloid-forming proteins, and another designed to target amyloid deposits. Overall, the reports suggest many patients can achieve blood and organ responses, but side effects were common and the studies were not designed to prove one approach is better than another. [14] [15]

In a 40-person, single-center retrospective study of relapsed AL amyloidosis, daratumumab monotherapy led to a blood response in 72.5% of patients, and heart response in 42.4% of those evaluable for heart response. People who achieved deeper blood responses and those who had a heart response had longer time before the disease worsened, and the treatment was described as generally well tolerated despite some serious side effects. [14]

In a 25-person phase 2, open-label study, anselamimab (CAEL-101) was added to standard anti-plasma cell therapy, including regimens with or without daratumumab. All participants experienced at least one health problem during treatment (most mild to moderate), serious events were reported in 64.0%, and 12.0% had fatal events; all serious and fatal events were judged unrelated to the study drug; the study also reported cardiac responses in 47.4% at Week 50 and kidney responses in 85.7% at later timepoints among evaluable participants. [15]

For patients and caregivers, these studies add context about how antibody-based treatments have been used in relapsed AL amyloidosis and in earlier-stage patients receiving standard therapy plus an anti-amyloid antibody. The daratumumab report is based on real-world experience at one center, while the anselamimab study is a small early-phase trial focused on safety, so both leave uncertainty about how results would compare in larger, randomized studies and across different patient groups.

Two reports looked beyond standard plasma cell treatment to therapies that may affect heart and kidney outcomes in people with amyloidosis. One large database study examined widely used heart medications and found a tradeoff between survival and side effects, and a separate single-patient report described an intensive cancer-treatment sequence that was followed by kidney improvement. [16] [17]

In a TriNetX retrospective study of cardiac amyloidosis with propensity-matched treated and untreated groups, use of ACE inhibitors, ARBs, or ARNi was linked to lower all-cause mortality over 3 years but higher hospitalization. Side effects including acute kidney injury, high potassium, and dizziness were more common with these drugs, and the survival benefit was seen in AL amyloidosis but not in transthyretin (ATTR) amyloidosis. [16]

One case report described a 67-year-old man with systemic lupus erythematosus, multiple myeloma, and presumptive heavy-and-light-chain amyloidosis who received induction chemotherapy, autologous stem cell transplant, and BCMA-targeted CAR T-cell therapy (cilta-cel). He achieved complete bone marrow remission and had substantial kidney improvement with reduced protein in the urine and stable kidney function by month 22, alongside ongoing issues like mild low blood counts and need for intravenous immunoglobulin support. [17]

These reports are most relevant as background for discussions about supportive care and intensive treatment options rather than as definitive guidance. The medication study suggests some heart drugs may be linked to longer survival in AL-related heart amyloidosis but may come with more hospitalizations and kidney/electrolyte side effects; because it was observational, it cannot prove the medicines caused the differences. The CAR T-cell report reflects one person with a complex overlap of conditions, so it cannot predict what will happen for others, but it documents what was feasible and what kinds of longer-term monitoring and support were needed.

Across these papers, heart problems in AL amyloidosis showed a wide range, including embolic events even when the heartbeat appears regular, conduction block needing a pacemaker, advanced heart failure with low blood pressure, and situations where multiple heart diseases occur together. A separate clinical study suggested that reduced beat-to-beat heart rhythm variation may track with cardiac involvement and worse stage, but its ability to predict outcomes remains uncertain. A lab-based tissue analysis added biological support for why the heart can stiffen over time, pointing to ongoing scarring (fibrosis) and remodeling in the heart muscle. Evidence strength was mostly exploratory and included several single-patient case reports plus one moderate-sized observational study and one smaller retrospective study. [18] [19] [20] [21] [22] [23] [24]

One case described an acute limb ischemia caused by an artery-blocking clot in a man with AL cardiac amyloidosis even though he remained in sinus rhythm, with testing suggesting the atrium was not squeezing effectively due to amyloid involvement. After starting daratumumab-based chemotherapy and the blood thinner apixaban, no further embolic events were reported during follow-up, and he had excellent functional recovery. Because this is a single case without extended rhythm monitoring, it cannot prove how often this pattern occurs or what best prevents recurrence. [18]

Several reports highlighted severe or unusual cardiac courses. One woman with advanced cardiac AL amyloidosis had a large improvement in blood markers after daratumumab-based therapy, yet her low blood pressure and right-sided heart weakness did not stabilize, and she died five months after presentation, showing that blood response and heart recovery can be out of sync in advanced disease. Another case described an epicardial mass that looked like cancer on imaging but was ultimately an amyloidoma on surgical biopsy; during the course, the patient developed advanced heart conduction block requiring a pacemaker. [20] [21]

In a retrospective study of 56 people with biopsy-proven AL amyloidosis, 24-hour heart rate variability (a measure of how the time between beats changes) was lower than in healthy controls, and abnormalities were more common in those with cardiac involvement seen on heart scans. One measure declined stepwise with worse Mayo 2004 stage, and in a smaller follow-up subset most measures did not change much after short-term therapy, suggesting this kind of monitoring might reflect underlying disease burden but needs prospective validation for prognosis. Separately, a single-center study from Egypt described long diagnostic delays and high mortality in cardiac amyloidosis overall, with AL being the most common subtype, and highlighted how limited access to key diagnostic tools can affect diagnosis and care pathways. [22] [23]

Two papers addressed complexity in diagnosis and biology. One transplant case report described a patient whose removed heart showed three coexisting conditions (sarcoidosis, AL amyloidosis, and transthyretin amyloidosis), with the new heart working well and no clinically significant rejection at 90 days, emphasizing that more than one disease process can contribute to an infiltrative cardiomyopathy picture. In heart tissue and lab experiments, another study found increased activity of genes linked to fibroblast activation and scarring, and showed that AL-related blood proteins could directly stimulate heart fibroblasts in vitro, supporting the idea that fibrosis is part of the cardiac injury process in AL amyloidosis. [19] [24]

For patients and caregivers, these studies reinforce that heart involvement in AL amyloidosis can lead to different types of complications: clots/emboli, rhythm or conduction problems, low blood pressure, and progressive stiffness or scarring of the heart muscle. Most of the detailed complication examples came from single-patient reports, so they describe what can happen but do not show how common each issue is. The larger observational studies mainly add context about monitoring (heart rhythm variability) and real-world challenges (diagnostic delays and limited test access), while the tissue study is background research that may inform future biomarker or targeted research but is not yet a clinical tool.

This month, research on non-heart organ involvement in AL amyloidosis (kidneys, lungs, gut, and muscles) mainly came from one moderate-strength kidney biopsy cohort and several single-patient reports. Overall, these papers reinforce that AL amyloidosis can look very different depending on where deposits occur, and that tissue confirmation (biopsy) was often central when symptoms or scans were unclear. What remains uncertain is how often these specific presentations occur and how well individual case outcomes apply to others.

In a 126-person retrospective kidney biopsy study focused on intratubular light chain amyloidosis (amyloid mainly in kidney tubules), kidney outcomes differed by accompanying kidney injury patterns. The subgroup that also had light chain cast nephropathy had the worst kidney outcomes, and the blood creatinine level at the time of biopsy independently predicted kidney prognosis. The authors also noted that cases that looked isolated to kidney tubules could later progress to multiple myeloma or systemic AL amyloidosis. [25]

Several reports focused on amyloid in the lungs, showing that transbronchial lung biopsy (a small sample taken via bronchoscopy) provided diagnostic tissue in different lung patterns. In a three-patient series, biopsy helped distinguish localized nodules (including lesions that could resemble cancer on scans) from diffuse alveolar-septal disease that turned out to be part of systemic AL amyloidosis, including one patient who also had multiple myeloma. No biopsy complications were reported in this small series. [26]

A separate single-patient report described AL (lambda) pulmonary amyloidosis presenting like interstitial lung disease; bronchoalveolar lavage fluid testing was not diagnostic, but a transbronchial lung biopsy confirmed amyloid type. After daratumumab plus cyclophosphamide, bortezomib, and dexamethasone, the patient had improved blood markers and stable lung function measures during follow-up. Because this is one person, it cannot show how often similar improvement occurs. [27]

Gastrointestinal involvement appeared in two very different case reports. One patient with recurrent uterine cancer had chronic bloating after meals before developing a jejunal (small bowel) perforation, and amyloid deposits were found in cancer tissue specimens, highlighting diagnostic complexity when serious illness overlaps with amyloidosis. [28]

Another report described localized gastric AL amyloidosis (kappa) found during endoscopic surveillance, followed six months later by discovery of a gastric MALT lymphoma with plasmacytic differentiation. In that case, an older chemical test suggested a different amyloid type, while immunohistochemistry supported AL, underscoring that amyloid typing methods can disagree. [29]

Muscle and nerve-related symptoms were highlighted in one systemic AL case with proximal muscle weakness and autonomic symptoms (such as dizziness with standing and gastrointestinal issues), alongside cardiac conduction disease. Diagnosis ultimately required a heart biopsy after abnormal scan uptake, and some non-heart symptoms (including swallowing trouble and chronic diarrhea) improved when blood markers improved, although neuropathy during therapy was also reported. As a single case, it mainly illustrates the range of symptoms and the need for multiple specialties. [30]

Three additional case reports, while centered on heart involvement, also included kidney or systemic features relevant to this topic group and tracked organ changes alongside blood marker responses. These included a woman with heart, kidney, and liver involvement who had improved heart function measures and reduced urine protein after cyclophosphamide, bortezomib, and dexamethasone; a man whose amyloid involved the heart and temporal artery and who reached blood marker remission with stable heart imaging; and a woman whose wearable-detected fast resting heart rate helped trigger evaluation leading to AL diagnosis and long-term improvement in heart-related measures during therapy. These are individual experiences and do not establish typical outcomes. [31] [32] [8]

One additional retrospective study compared heart ultrasound and blood marker patterns in AA amyloidosis versus AL amyloidosis and other heart conditions. Because it primarily focused on AA amyloidosis rather than AL, it provides background about how heart structure and blood markers were linked with mortality risk in that different amyloid type, and it does not directly answer kidney, lung, gut, or muscle questions in AL. [33]

For patients and caregivers, these papers mainly add context rather than changing care today: they show how varied AL amyloidosis can be outside the heart, and why biopsy-based confirmation and accurate amyloid typing matter when symptoms involve the kidneys, lungs, gut, or muscles. The kidney cohort suggests that the specific pattern seen on kidney biopsy and kidney function at diagnosis were linked to later kidney outcomes, while the lung and gut reports illustrate that uncommon presentations may require targeted biopsies to clarify what is going on. The biggest uncertainty is generalizability: most non-kidney data here are single cases or very small series, so they cannot predict what will happen for any individual person.