Graded Cardiac Response Criteria for Patients With Systemic Light Chain Amyloidosis

Abstract

PURPOSE Binary cardiac response assessment using cardiac biomarkers is prognostic in light chain amyloidosis. Previous studies suggested four-level cardiac responses using N-terminal prohormone of brain natiuretic peptide improves prognostic prediction. This study was designed to validate graded cardiac response criteria using N-terminal prohormone of brain natiuretic peptide/brain natiuretic peptide. PATIENTS AND METHODS This retrospective, multicenter study included patients with light chain amyloidosis who achieved at least a hematologic partial response (PR) and were evaluable for cardiac response. Four response criteria were tested on the basis of natriuretic peptide response depth: cardiac complete response (CarCR), cardiac very good partial response (CarVGPR), cardiac PR (CarPR), and cardiac no response (CarNR). Response was classified as best response and at fixed time points (6, 12, and 24 months from therapy initiation). The study primary outcome was overall survival. RESULTS 651 patients were included. Best CarCR, CarVGPR, CarPR, and CarNR were achieved in 16%, 26.4%, 22.9%, and 34.7% of patients, respectively. Patients in cardiac stage II were more likely to achieve CarCR than patients in cardiac stage IIIA and IIIB (22% v 13.5% v 3.2%; P < .001). A deeper cardiac response was associated with a longer survival (5-year overall survival 93%, 79%, 65%, and 33% for CarCR, CarVGPR, CarPR, and CarNR, respectively; P < .001). Fixed time-point analyses and time-varying covariates Cox regression analysis, to minimize survivorship bias, affirmed the independent survival advantage of deeper cardiac responses. Four-level response performed better than two-level response as early as 12 months from therapy initiation. CONCLUSION Graded cardiac response criteria allow better assessment of cardiac improvement compared with the traditional binary response system. The study re-emphasizes the importance of early diagnosis, which increases the likelihood of deep cardiac responses.

First report of outcomes in patients with stage IIIb AL amyloidosis treated with Dara–VCD front‐line therapy

“…All but one patient (who underwent a heart transplant within three months of treatment initiation) were evaluable for cardiac organ response. On an intention‐to‐treat basis, cardiac response was achieved by 10 patients (56%), and cardiac VGPR or better (as per criteria established by Muchtar et al 7 …”

“…Haematologic and organ response rates were adjudicated based on standard guidelines. 5,6 Grade of cardiac organ response was also calculated based on the criteria published by Muchtar et al 7 Overall survival (OS) was defined as time from treatment initiation to death due to any cause. Clinical data were extracted by review of electronic medical records.…”

Individualized Approach to Management of Light Chain Amyloidosis

“…Deepening of organ response over time (after 6-12 months) indicates that hematologic response is deep enough to allow improvement of organ involvement. 72 In the absence of other causes of organ dysfunction, the lack of this further improvement is more frequent in patients with no CR, 73 but this can also occur in patients with CR and persistence of MRD positivity. 47 Our current approach is to treat these patients if they are fit enough and if suitable treatments are accessible.…”

“…Moreover, organ response can be delayed and should not guide early treatment decision. Deepening of organ response over time (after 6-12 months) indicates that hematologic response is deep enough to allow improvement of organ involvement 72. In the absence of other causes of organ dysfunction, the lack of this further improvement is more frequent in patients with no CR,73 but this can also occur in patients with CR and persistence of MRD positivity 47.…”

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

“…New‐graded organ response criteria have been proposed for amyloidosis. For the heart no response, PR, VGPR, and CR are defined as less than 30% reduction in NT‐proBNP, 31% to 60% reduction in NT‐proBNP, greater than 60% reduction in NT‐proBNP, and NT‐proBNP less than or equal to 400 pg/mL, respectively 58 . For the kidney no response, PR, VGPR, and CR are defined as less than 30% reduction in proteinuria, 31% to 60% reduction in proteinuria, greater than 60% reduction in proteinuria, and less than 200 mg proteinuria per 24 h, respectively.…”