Cardiac impairment is associated with high morbidity and mortality in immunoglobulin light chain (AL) type amyloidosis, for which early identification and risk stratification is vital. For myocardial tissue characterization, late gadolinium enhancement (LGE) is a classic and most commonly performed cardiovascular magnetic resonance (CMR) parameter. T1 mapping with native T1 and extracellular volume (ECV) are recently developed quantitative parameters. We aimed to investigate the prognostic value of native T1, ECV and LGE in patients with AL amyloidosis. Eighty-two patients (55.5 ± 8.5 years; 52 M) and 20 healthy subjects (53.2 ± 11.7 years; 10 M) were prospectively recruited. All subjects underwent CMR with LGE imaging and T1 mapping using a Modified Look-Locker Inversion-recovery (MOLLI) sequence on a 3 T scanner. Native T1 and ECV were measured semi-automatically using a dedicated CMR software. The left ventricular (LV) LGE pattern was classified as none, patchy, and global groups. Global LGE was considered when there was diffuse, transmural LGE in more than half of the short axis images. Follow-up was performed for all-cause mortality using Cox proportional hazards regression analysis and Kaplan-Meier survival curves. The patients demonstrated an increase in native T1 (1438 ± 120 ms vs. 1283 ± 46 ms, P = 0.001) and ECV (43.9 ± 10.9% vs. 27.0 ± 1.7%, P = 0.001) compared to healthy controls. Native T1, ECV and LGE showed significant correlation with Mayo Stage, and ECV and LGE showed significant correlation with echocardiographic E/E’ and LV ejection fraction. During the follow-up for a median time of 8 months, 21 deaths occurred. ECV ≥ 44.0% (hazard ratio [HR] 7.249, 95% confidence interval (CI) 1.751–13.179, P = 0.002) and global LGE (HR 4.804, 95% CI 1.971–12.926, P = 0.001) were independently prognostic for mortality over other clinical and imaging parameters. In subgroups with the same LGE pattern, ECV ≥ 44.0% remained prognostic (log rank P = 0.029). Median native T1 (1456 ms) was not prognostic for mortality (Tarone-Ware, P = 0.069). During a short-term follow-up, both ECV and LGE are independently prognostic for mortality in AL amyloidosis. In patients with a similar LGE pattern, ECV remained prognostic. Native T1 was not found to be a prognostic factor.

The goal of hematological response has been well established in the treatment of systemic light chain amyloidosis. However, the pattern of cardiac response remains unknown. This study was designed to investigate the cardiac response dynamics in patients with an early and high-quality hematological response. This retrospective study included newly diagnosed patients who achieved a hematological response of very good partial response or better within 3 months after treatment beginning. Four cardiac response criteria were tested at fixed time points (3, 6, 12, and 24 months after therapy initiation): cardiac complete response, cardiac very good partial response, cardiac partial response (carPR), and cardiac no response. A total of 201 patients were included, with the median follow-up 37.0 months (Q1-Q3: 18.0-56.5 months). The cardiac response reached a plateau at 24 months, while cardiac complete response, cardiac very good partial response, and carPR were achieved in 21.4% (28 of 131), 38.9% (51 of 131), and 20.6% (27 of 131) of the patients, respectively. At every fixed time point within 12 months after treatment initiation, patients who achieved a carPR or better consistently had better survival than did those who did not. At 3 months, an NT-proBNP concentration ≥3,716 pg/mL was the only factor associated with a decreased likelihood of achieving a carPR within 12 months (OR: 0.269; 95% CI: 0.137-0.512; P < 0.001). This study emphasizes the importance of monitoring cardiac response dynamics for disease surveillance. In patients who achieve early and high-quality hematological response, it is important to achieve carPR within 12 months.

Few studies have reported that venetoclax, a selective BCL2 inhibitor, has shown promising efficacy in relapsed/refractory AL amyloidosis (RRAL), especially among patients harboring t(11;14). We retrospectively reviewed 29 RRAL patients treated with venetoclax between July 2022 and January 2025. Treatment was given for suboptimal prior response (45%), hematologic progression (38%), or rising involved free light chain not meeting progression criteria (17%). Venetoclax induced rapid and deep responses: 79% achieved very good partial response (VGPR) or complete response (CR), and 52% achieved stringent FLC response. High t(11;14) (> 10%) patients achieved ≥ VGPR in 91% versus 33% in low t(11;14) (p = 0.008). Cardiac responses occurred in 59% of evaluable patients. At a median follow-up of 19.7 months, one-year overall survival and event-free survival were 96.6% and 82.6%, respectively; two deaths were due to cardiac progression. Venetoclax was well tolerated, with mostly grade 1–2 adverse events, except one grade 3 leukopenia/neutropenia with grade 3 infection. These results support venetoclax as an effective and safe therapy for RRAL, particularly in t(11;14) patients, and highlight the need for prospective studies to refine patient selection and optimize treatment strategies.

Light chain (AL) amyloidosis is a systemic disorder caused by plasma cell dyscrasia, with cardiac involvement being the primary determinant of prognosis. Survival outcomes vary significantly across disease stages. This heterogeneity underscores a critical need for early diagnosis, precise risk stratification, and response-adapted therapy. In this context, multimodality imaging has emerged as an indispensable non-invasive tool, providing crucial insights for clinical decision-making. This review synthesizes recent advances in the application of key imaging modalities—echocardiography, magnetic resonance imaging, and nuclear medicine imaging—for evaluating AL amyloidosis. We highlight how these techniques have shifted the paradigm from anatomical assessment to quantitative, multiparametric tissue characterization, ultimately guiding personalized patient management.

Summary: Anti‐CD38 monoclonal antibodies dramatically improve the prognosis in immunoglobulin light‐chain (AL) amyloidosis, yet patients with end‐stage (Mayo 2004 IIIB) disease are typically excluded from prospective trials. To evaluate the daratumumab plus bortezomib and dexamethasone (Dara‐VD) regimen in Mayo 2004 stage III patients, we conducted a prospective phase 2 trial including 20 stage IIIA and 20 stage IIIB patients. The long‐term follow‐up results are reported here. The 24‐month haematological complete response (CR) and very good partial response (VGPR) rate were 52.5% and 12.5% respectively. Organ responses improved after 12 months; the 24‐month cardiac CR and VGPR rates were 15.0% and 35.0%. After a median follow‐up of 50.9 months, 16 patients died and 10 patients had progressive diseases. The median overall survival (OS) had not been reached in either group, with a 4‐year OS rate of 60.0% (95% confidence interval [CI]: 45.2%–75.2%). The median event‐free survival (EFS) was 33.5 months (95% CI 21.0–46.0 months), with a 4‐year EFS rate of 37.5% (95% CI: 24.3–54.7). No significant difference in OS or EFS was observed between stage IIIA and IIIB patients. In conclusion, the strong anti‐plasma cell regimen Dara‐VD provides comparable long‐term responses and prognosis for Mayo stage IIIB patients.