Renal outcomes in patients with AL amyloidosis: Prognostic factors, renal response and the impact of therapy

Kastritis, Efstathios; Gavriatopoulou, Maria; Ρούσσου, Μαρία; Migkou, Magdalini; Fotiou, Despina; Ziogas, Dimitrios C.; Kanellias, Nikos; Eleutherakis‐Papaiakovou, Evangelos; Panagiotidis, Ioannis; Giannouli, Stavroula; Psimenou, Erasmia; Marinaki, Smaragdi; Apostolou, Theofanis; Gakiopoulou, Hariklia; Tasidou, Anna; Papassotiriou, Ioannis; Terpos, Evangelos

doi:10.1002/ajh.24738

Cited by 59 publications

(70 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of importance, 4/5 patients without a renal response had no hematological response and the fifth had only a partial hematological response. Three of these five patients had AL or AL/AH amyloidosis, a nephropathy characterized by its inconstant renal response to therapy . Our findings confirm that a complete hematological response is the main predictor for a prolonged renal response, but also that an early response is desirable.…”

Section: Discussionsupporting

confidence: 76%

Bendamustine plus rituximab for indolent B‐cell lymphoma of renal significance

et al. 2017

View full text Add to dashboard Cite

Treatment of indolent B-cell non-Hodgkin lymphomas (iNHL) of renal significance is challenging given the need for deep and prolonged hematological response to restore and control renal function overtime, yet to be balanced with the risk of adverse drug-related events. This prospective single-center study included 20 patients with iNHL of renal significance (tubulointerstitial presentation [n = 8], glomerulopathy with or without monoclonal Ig deposits [n = 12]) who received a steroid-sparing regimen of rituximab plus bendamustine (BR), with either no or<1 month of steroid intake (as a first line therapy in 80%). Seventeen patients (85%) achieved a complete (CHR, n = 12) or a partial (PHR, n = 5) hematological response. Nine out of the 12 patients (75%) with iNHL-related glomerulopathy had a complete (CRR) or a partial (PRR) renal response. Among the six patients with glomerulopathy and CHR, five had a CRR (83%) compared to 1/6 (17%) that did not reach CHR. eGFR increased from 38 to 58 mL/min/1.73 m , and returned to baseline in five patients. Among the eight patients with a tubulointerstitial presentation, six (75%) had a renal response (5 CRR), and eGFR increased from 29 to 48 mL/min/1.73 m . One patient with a PHR had a renal relapse. Mortality rate was 10% at 12 months. The BR regimen was well tolerated overall. Thus, despite severe renal disease at presentation, a relapsing iNHL in 20% of patients and several comorbidities, the BR regimen was efficient and safe in our series. It should be further assessed as a first line therapy for patients with iNHL of renal significance.

show abstract

Section: Discussionsupporting

confidence: 76%

Bendamustine plus rituximab for indolent B‐cell lymphoma of renal significance

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The Mayo Clinic group incorporated the dFLC level (with a cutoff value of 180 mg/L) in their revised staging system ( Figure 6B) 77,78 . A renal staging system predicting the progression to dialysis has also been proposed and validated by European investigators ( Figure 6C) 60,79 Although the severity of renal involvement does not directly affect survival, it impacts kidney survival, QOL and might reduce access to effective therapy. Other biomarkers have been shown to predict outcomes in systemic AL amyloidosis, but have not been integrated in staging systems so far.…”

Section: [H2] Patient Risk Stratificationmentioning

confidence: 99%

Systemic immunoglobulin light chain amyloidosis

Merlini

Dispenzieri

Sanchorawala

et al. 2018

Nat Rev Dis Primers

428

387

View full text Add to dashboard Cite

Systemic immunoglobulin light chain (AL) amyloidosis is a protein misfolding disease that is caused by the conversion of immunoglobulin light chains from their soluble functional states into highly organized amyloid fibrillar aggregates that lead to organ dysfunction. The disease is progressive and, accordingly, early diagnosis is vital to prevent irreversible organ damage, of which cardiac and renal damage predominate. The development of novel sensitive biomarkers and imaging technologies for the detection and quantification of organ involvement and damage are facilitating earlier diagnosis and enhanced evaluation of the efficacy of new and existing therapies. Treatment is guided by risk assessment which is based on levels of cardiac biomarkers; close monitoring of clonal and organ response guides duration of therapy and changes in regimen. Several new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, along with high-dose chemotherapy and autologous haematopoietic stem cell transplantation, have led to rapid and deep suppression of the amyloid light chain production in the majority of patients. However, effective therapies for patients with advanced cardiac involvement are an unmet need. Passive immunotherapies targeting clonal plasma cells and directly accelerating removal of amyloid deposits promise to further improve the overall outlook of this increasingly treatable disease.

show abstract

“…(Kumar et al , ; Dittrich et al , ; Milani et al , ; Sidana et al , ) In another series of 77 systemic AL amyloid patients with renal involvement, Wong et al () observed median dFLC levels 127 mg/l, with 60% of patients in this series having co‐existing cardiac involvement. Similarly, Kastritis et al () described a series of 125 patients with renal involvement, of whom 42% had co‐existing cardiac involvement. Median involved FLC levels were: 166 mg/l.…”

Section: Discussionmentioning

confidence: 93%

Clinical features, laboratory characteristics and outcomes of patients with renal versus cardiac light chain amyloidosis

et al. 2019

View full text Add to dashboard Cite

Summary This study evaluated the differences in clinical features of 1077 newly diagnosed AL amyloidosis patients with renal involvement (n = 229, 21%), both cardiac and renal involvement (n = 443, 41%) and cardiac involvement (n = 405, 38%). Significant differences in dFLC (difference in involved and uninvolved light chains) were noted (renal, both, cardiac median: 83, 234 and 349 mg/l, P < 0.001). The proportion of patients with ≥ 10% bone marrow plasma cells (BMPCs) was lowest in renal only patients: 44%, 57%, 64%, respectively, P < 0.001. In a multivariate linear regression model incorporating organ involvement type and BMPCs ≥10%, organ involvement was a significant predictor of dFLC (P < 0.001). Median overall survival (OS) across the three groups was 83 vs. 19 vs. 16 months (P < 0.001) in patients not undergoing transplant and 5‐year OS in patients undergoing transplant was 90% vs. 75% vs. 64% (P = 0.007), respectively. In conclusion, renal involvement alone or renal + cardiac involvement in AL amyloidosis is associated with lower circulating light chain burden, which cannot be fully explained by BMPC burden alone. Increased sensitivity of the kidney to light chains, given significant interactions with the renal tubular system and secretion of modified light chain products may play a role in pathogenesis of renal AL amyloidosis and warrants further investigation.

show abstract

Renal outcomes in patients with AL amyloidosis: Prognostic factors, renal response and the impact of therapy

Cited by 59 publications

References 27 publications

Bendamustine plus rituximab for indolent B‐cell lymphoma of renal significance

Bendamustine plus rituximab for indolent B‐cell lymphoma of renal significance

Systemic immunoglobulin light chain amyloidosis

Clinical features, laboratory characteristics and outcomes of patients with renal versus cardiac light chain amyloidosis

Contact Info

Product

Resources

About