Skip to main content

14.05.2024 | IM - ORIGINAL

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

verfasst von: Yan Xing, Xiayin Li, Jin Zhao, Hao Wu, Lijuan Zhao, Wanting Zheng, Shiren Sun

Erschienen in: Internal and Emergency Medicine

Einloggen, um Zugang zu erhalten

Abstract

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 ≤ 50 mL/min/1.73 m2, interventricular septum ≥ 15 mm, 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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
4.
5.
Zurück zum Zitat Palladini G et al (2023) The management of light chain (AL) amyloidosis in Europe: clinical characteristics, treatment patterns, and efficacy outcomes between 2004 and 2018. Blood Cancer J 13(1):19CrossRefPubMedPubMedCentral Palladini G et al (2023) The management of light chain (AL) amyloidosis in Europe: clinical characteristics, treatment patterns, and efficacy outcomes between 2004 and 2018. Blood Cancer J 13(1):19CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Muchtar E et al (2017) Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death. Blood 129(15):2111–2119CrossRefPubMedPubMedCentral Muchtar E et al (2017) Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death. Blood 129(15):2111–2119CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Kumar S et al (2012) Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol 30(9):989–995CrossRefPubMedPubMedCentral Kumar S et al (2012) Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol 30(9):989–995CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Oubari S et al (2024) Daratumumab in first-line treatment of patients with light chain amyloidosis and Mayo stage IIIb improves treatment response and overall survival. Haematologica 109(1):220–230PubMed Oubari S et al (2024) Daratumumab in first-line treatment of patients with light chain amyloidosis and Mayo stage IIIb improves treatment response and overall survival. Haematologica 109(1):220–230PubMed
9.
Zurück zum Zitat Kastritis E et al (2021) Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med 385(1):46–58CrossRefPubMed Kastritis E et al (2021) Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med 385(1):46–58CrossRefPubMed
10.
Zurück zum Zitat Wechalekar AD et al (2023) Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group. Amyloid 30(1):3–17CrossRefPubMed Wechalekar AD et al (2023) Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group. Amyloid 30(1):3–17CrossRefPubMed
13.
Zurück zum Zitat Jamet B et al (2021) Random survival forest to predict transplant-eligible newly diagnosed multiple myeloma outcome including FDG-PET radiomics: a combined analysis of two independent prospective European trials. Eur J Nucl Med Mol Imaging 48(4):1005–1015CrossRefPubMed Jamet B et al (2021) Random survival forest to predict transplant-eligible newly diagnosed multiple myeloma outcome including FDG-PET radiomics: a combined analysis of two independent prospective European trials. Eur J Nucl Med Mol Imaging 48(4):1005–1015CrossRefPubMed
14.
Zurück zum Zitat Bohannan ZS, Coffman F, Mitrofanova A (2022) Random survival forest model identifies novel biomarkers of event-free survival in high-risk pediatric acute lymphoblastic leukemia. Comput Struct Biotechnol J 20:583–597CrossRefPubMedPubMedCentral Bohannan ZS, Coffman F, Mitrofanova A (2022) Random survival forest model identifies novel biomarkers of event-free survival in high-risk pediatric acute lymphoblastic leukemia. Comput Struct Biotechnol J 20:583–597CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Rajkumar SV et al (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15(12):e538–e548CrossRefPubMed Rajkumar SV et al (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15(12):e538–e548CrossRefPubMed
16.
Zurück zum Zitat Gertz MA et al. (2005) Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18–22 Apr 2004. pp. 319–328 Gertz MA et al. (2005) Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18–22 Apr 2004. pp. 319–328
17.
Zurück zum Zitat Collins GS et al (2015) Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. BMJ (Clin Res Ed) 350:g7594 Collins GS et al (2015) Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. BMJ (Clin Res Ed) 350:g7594
18.
Zurück zum Zitat Garcia-Garcia HM et al (2019) Impact of periprocedural myocardial biomarker elevation on mortality following elective percutaneous coronary intervention. JACC Cardiovasc Interv 12(19):1954–1962CrossRefPubMed Garcia-Garcia HM et al (2019) Impact of periprocedural myocardial biomarker elevation on mortality following elective percutaneous coronary intervention. JACC Cardiovasc Interv 12(19):1954–1962CrossRefPubMed
20.
Zurück zum Zitat Brenner DA et al (2004) Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in cellular oxidant stress. Circ Res 94(8):1008–1010CrossRefPubMed Brenner DA et al (2004) Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in cellular oxidant stress. Circ Res 94(8):1008–1010CrossRefPubMed
21.
Zurück zum Zitat Ghio S et al (2007) Importance of the echocardiographic evaluation of right ventricular function in patients with AL amyloidosis. Eur J Heart Fail 9(8):808–813CrossRefPubMed Ghio S et al (2007) Importance of the echocardiographic evaluation of right ventricular function in patients with AL amyloidosis. Eur J Heart Fail 9(8):808–813CrossRefPubMed
22.
Zurück zum Zitat Wang X et al (2022) Feasibility of (68)Ga-labeled fibroblast activation protein inhibitor PET/CT in light-chain cardiac amyloidosis. JACC Cardiovasc Imaging 15(11):1960–1970CrossRefPubMed Wang X et al (2022) Feasibility of (68)Ga-labeled fibroblast activation protein inhibitor PET/CT in light-chain cardiac amyloidosis. JACC Cardiovasc Imaging 15(11):1960–1970CrossRefPubMed
23.
Zurück zum Zitat Gertz MA, Kyle RA (1988) Hepatic amyloidosis (primary [AL], immunoglobulin light chain): the natural history in 80 patients. Am J Med 85(1):73–80CrossRefPubMed Gertz MA, Kyle RA (1988) Hepatic amyloidosis (primary [AL], immunoglobulin light chain): the natural history in 80 patients. Am J Med 85(1):73–80CrossRefPubMed
24.
Zurück zum Zitat Park MA et al (2003) Primary (AL) hepatic amyloidosis: clinical features and natural history in 98 patients. Medicine 82(5):291–298CrossRefPubMed Park MA et al (2003) Primary (AL) hepatic amyloidosis: clinical features and natural history in 98 patients. Medicine 82(5):291–298CrossRefPubMed
25.
Zurück zum Zitat Rosenzweig M, Kastritis E (2020) Liver and gastrointestinal involvement: update. Hematol Oncol Clin North Am 34(6S):e1–e13CrossRefPubMed Rosenzweig M, Kastritis E (2020) Liver and gastrointestinal involvement: update. Hematol Oncol Clin North Am 34(6S):e1–e13CrossRefPubMed
26.
Zurück zum Zitat Borovac JA et al (2020) Right ventricular free wall strain and congestive hepatopathy in patients with acute worsening of chronic heart failure: a CATSTAT-HF echo substudy. J Clin Med 9(5):1317CrossRefPubMedPubMedCentral Borovac JA et al (2020) Right ventricular free wall strain and congestive hepatopathy in patients with acute worsening of chronic heart failure: a CATSTAT-HF echo substudy. J Clin Med 9(5):1317CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Migrino RQ et al (2009) Left ventricular ejection time on echocardiography predicts long-term mortality in light chain amyloidosis. J Am Soc Echocardiogr 22(12):1396–1402CrossRefPubMedPubMedCentral Migrino RQ et al (2009) Left ventricular ejection time on echocardiography predicts long-term mortality in light chain amyloidosis. J Am Soc Echocardiogr 22(12):1396–1402CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Dittrich T et al (2019) Performance analysis of AL amyloidosis cardiac biomarker staging systems with special focus on renal failure and atrial arrhythmia. Haematologica 104(7):1451–1459CrossRefPubMedPubMedCentral Dittrich T et al (2019) Performance analysis of AL amyloidosis cardiac biomarker staging systems with special focus on renal failure and atrial arrhythmia. Haematologica 104(7):1451–1459CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Palladini G et al (2014) A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood 124(15):2325–2332CrossRefPubMed Palladini G et al (2014) A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood 124(15):2325–2332CrossRefPubMed
30.
Zurück zum Zitat Jimenez-Zepeda V et al (2023) A comprehensive multidisciplinary diagnostic algorithm for the early and efficient detection of amyloidosis. Clin Lymphoma Myeloma Leuk 23(3):194–202CrossRefPubMed Jimenez-Zepeda V et al (2023) A comprehensive multidisciplinary diagnostic algorithm for the early and efficient detection of amyloidosis. Clin Lymphoma Myeloma Leuk 23(3):194–202CrossRefPubMed
31.
Zurück zum Zitat Yan W et al (2021) A prognostic staging system for light-chain amyloidosis using hepatic and renal indicator data from 1,064 Chinese patients. Ann Transl Med 9(16):1347–1347CrossRefPubMedPubMedCentral Yan W et al (2021) A prognostic staging system for light-chain amyloidosis using hepatic and renal indicator data from 1,064 Chinese patients. Ann Transl Med 9(16):1347–1347CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Dispenzieri A et al (2003) Survival in patients with primary systemic amyloidosis and raised serum cardiac troponins. Lancet 361(9371):1787–1789CrossRefPubMed Dispenzieri A et al (2003) Survival in patients with primary systemic amyloidosis and raised serum cardiac troponins. Lancet 361(9371):1787–1789CrossRefPubMed
34.
Zurück zum Zitat Palladini G et al (2010) The combination of high-sensitivity cardiac troponin T (hs-cTnT) at presentation and changes in N-terminal natriuretic peptide type B (NT-proBNP) after chemotherapy best predicts survival in AL amyloidosis. Blood 116(18):3426–3430CrossRefPubMed Palladini G et al (2010) The combination of high-sensitivity cardiac troponin T (hs-cTnT) at presentation and changes in N-terminal natriuretic peptide type B (NT-proBNP) after chemotherapy best predicts survival in AL amyloidosis. Blood 116(18):3426–3430CrossRefPubMed
35.
Zurück zum Zitat Kumar S et al (2023) Impact of cytogenetic abnormalities on treatment outcomes in patients with amyloid light-chain amyloidosis: subanalyses from the ANDROMEDA study. Amyloid 30(3):268–278CrossRefPubMed Kumar S et al (2023) Impact of cytogenetic abnormalities on treatment outcomes in patients with amyloid light-chain amyloidosis: subanalyses from the ANDROMEDA study. Amyloid 30(3):268–278CrossRefPubMed
36.
Zurück zum Zitat Chakraborty R et al (2023) First report of outcomes in patients with stage IIIb AL amyloidosis treated with Dara-VCD front-line therapy. Br J Haematol 201(5):913–916CrossRefPubMed Chakraborty R et al (2023) First report of outcomes in patients with stage IIIb AL amyloidosis treated with Dara-VCD front-line therapy. Br J Haematol 201(5):913–916CrossRefPubMed
Metadaten
Titel
Advancing precision medicine in immunoglobulin light-chain amyloidosis: a novel prognostic model incorporating multi-organ indicators
verfasst von
Yan Xing
Xiayin Li
Jin Zhao
Hao Wu
Lijuan Zhao
Wanting Zheng
Shiren Sun
Publikationsdatum
14.05.2024
Verlag
Springer International Publishing
Erschienen in
Internal and Emergency Medicine
Print ISSN: 1828-0447
Elektronische ISSN: 1970-9366
DOI
https://doi.org/10.1007/s11739-024-03621-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.