FC 039RENAL OUTCOME AFTER RITUXIMAB IN ADULT-ONSET IGA VASCULITIS AND CRESCENTIC IGA NEPHROPATHY: A MULTICENTRE STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Giorgio Trivioli ◽  
Alice Canzian ◽  
Federica Maritati ◽  
Roberta Fenoglio ◽  
Evangeline Pillebout ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Disease ◽  
Iga Nephropathy ◽  
Immunosuppressive Agents ◽  
Renal Involvement ◽  
Renal Outcome ◽  
Iga Vasculitis ◽  
Adult Onset ◽  
Free Survival

Abstract Background and Aims Glucocorticoids (GC) and/or immunosuppressive agents are the mainstay of therapy for adult-onset IgA Vasculitis (IgAV), but their efficacy is often partial while their toxicity is relevant. Recently, rituximab (RTX) has been reported as a safe and effective option but only few data on renal outcome are available.1 RTX has also been used in a few cases of crescentic IgA Nephropathy (cIgAN), an IgAN subset with vasculitic lesions and poor response to conventional immunosuppressive regimens.2 We present the results of a multicentre cohort of patients with IgAV and cIgAN treated with RTX. Method The databases of 16 consorted European centres were investigated to screen for patients with adult-onset, biopsy-proven IgAV and cIgAN (crescents in ≥25% glomeruli and rapid eGFR worsening at presentation), who received RTX as induction therapy. We selected patients with active renal manifestations at the time of RTX. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS)=0 or <5 if it was due to persistent proteinuria and relapse as an increase in BVAS requiring change in immunosuppressive therapy. Results We identified 38 patients with IgAV and 12 patients with cIgAN who received RTX and had active renal involvement at the time of treatment. The median age at onset was 40 years (interquartile range, IQR, 25-53) and more than two-thirds of patients were male (Table 1). The median follow-up after RTX was 41 months (IQR 18-60). Renal outcomes are reported in Table 2. At the time of treatment, 24 patients (48%) had eGFR ≥60 mL/min/1.73 m2. All had IgAV and their median BVAS was 17 (IQR 10-22). Furthermore, all had microhaematuria and proteinuria. Renal histology showed mesangial or focal endocapillary proliferation in 12/17 (71%) patients who underwent biopsy (class II-IIIA according to Pillebout3). Twenty patients (83%) achieved remission; after a median of 12 months (range 9-14), four experienced a minor relapse and one had a major relapse with significant renal disease progression. Renal function remained stable in all but two patients who developed end-stage renal disease (ESRD). Micro-haematuria subsided in 14/24 (58%) and median 24h proteinuria decreased from 1750 mg (IQR 865-3275) to 175 mg (IQR 100-800) at last follow-up (p=0.029). Of the 26 patients with eGFR <60 mL/min/1.73 m2, 14 had IgAV and 12 had cIgAN. All were biopsied and 20 (77%) had diffuse endo/extra-capillary proliferation (classes IIIB-IV). Five patients required dialysis but recovered soon after treatment start. Remission was achieved by 16/26 (61%); eight (50%) subsequently relapsed and two (12%) reached ESRD. At last follow-up, eGFR was ≥60 mL/min/1.73 m2 in 8/26 (31%), 10/26 (48%) had stable renal function as compared to the time of RTX, while 8/26 (31%) had developed ESRD. Median 24h proteinuria decreased from 3400 mg (IQR 2150-6500) to 770 mg (177-1315) (p=0.016). Remission rate and ESRD-free survival were respectively 86% and 92% in patients with IgAV, while they were respectively 42% and 42% in cIgAN patients. Furthermore, 21/24 (87%) patients who received RTX alone or combined to glucocorticoids but not to immunosuppressive agents achieved remission and 22/24 (92%) were ESRD-free at last follow-up. Of the 26 patients receiving immunosuppressive agents, 17 (65%) obtained remission and 18 (69%) were ESRD-free at last assessment. Over the whole follow-up, only one patient reported a severe adverse effect related to RTX (pneumonia). Conclusion Renal involvement in adult-onset IgAV and cIgAN is frequently severe. RTX, combined or not with other immunosuppressive agents, may improve renal manifestations and is well tolerated. IgAV patients show higher remission rates and a longer ESRD-free survival as compared to cIgAN patients.

scholarly journals Serum Concentrations of Laminin-P1 in Thrombotic Microangiopathy

2000 ◽  
Vol 11 (3) ◽  
pp. 434-443
Author(s):  
ALFONS SEGARRA ◽  
RAFAEL SIMÓ ◽  
LLUIS MASMIQUEL ◽  
ROSA M. SEGURA ◽  
VICENS FONOLLOSA ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Basement Membrane ◽  
Renal Involvement ◽  
Serum Levels ◽  
Renal Outcome ◽  
Serum Concentrations ◽  
Healthy Control ◽  
Regular Hemodialysis

Abstract. Laminin is the main noncollagenous constituent of the basement membrane, and its serum levels could reflect the metabolic changes that occur in the basement membrane. Severe endothelial injury with thickening of basement membrane is a characteristic feature of thrombotic microangiopathy (TMA). With this background, the aim of the study was to investigate in a prospective way (1) the relationship among serum Lam-P1, the extent of renal histopathologic lesions, and the biochemical parameters commonly used as markers of TMA activity, and (2) the usefulness of serum Lam-P1 concentrations as a renal outcome prognostic index. To this end, 18 consecutive patients with active biopsy-proven TMA with renal involvement were studied. One hundred and twenty-one healthy control subjects, 20 patients with systemic scleroderma without renal involvement, and 35 patients with systemic lupus erythematosus (20 without nephropathy and 15 with diffuse proliferative type 4 lupus nephritis) were used as control groups. In addition, to analyze the influence of either renal failure or hemodialysis therapy on serum Lam-P1 levels, 91 patients on regular hemodialysis therapy and 81 patients with predialysis chronic renal failure of different etiologies were included in the study. Serum Lam-P1 was determined by RIA at admission, on days 10 and 30 of follow-up in all patients, and after 6 and 12 mo of follow-up in all surviving patients. Serum lactate dehydrogenase, haptoglobin, platelet count, hemoglobin, and serum creatinine were determined as markers of endothelial dysfunction and hemolysis. At admission, serum levels of Lam-P1 were significantly higher in patients with TMA than in healthy control subjects (3.39 ± 0.56 U/ml versus 1.40 ± 0.18 U/ml; P < 0.0001). In addition, patients with TMA had significantly higher serum Lam-P1 levels than the other groups included in the study. At the first control, Lam-P1 correlated with lactate dehydrogenase (P = 0.006) and hemoglobin (P = 0.002). During follow-up, platelet count and hemolysis indicators normalized in all patients, while serum Lam-P1 decreased only in patients with renal function recovery. In multivariate analysis, serum creatinine and Lam-P1 at day 10 were the only independent predictors of renal outcome (r2 = 0.94; P < 0.0001) and also correlated with indices of histopathologic damage (P < 0.001). Serum Lam-P1 normalized in all patients with chronic renal failure in the samples obtained at 6 and 12 mo of regular hemodialysis after solving active TMA, thus suggesting that histopathologic lesions, but not renal function itself, would be mainly responsible for the high Lam-P1 serum concentrations detected in TMA. In conclusion, serum Lam-P1 concentrations are increased in patients with active TMA. Furthermore, patients with poor renal outcome show a prolonged increase of serum Lam-P1 that is related to the extent of renal histologic lesions. Unlike the biochemical markers of hemolysis commonly used to assess TMA activity, the sequential determination of serum Lam-P1 provides valuable information about long-term renal prognosis in patients with TMA.

P0206RITUXIMAB IN ADULT ONSET OF IGA VASCULITIS WITH SEVERE RENAL INVOLVEMENT: A SINGLE CENTER EXPERIENCE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Roberta Fenoglio ◽  
Martina Cozzi ◽  
Savino Sciascia ◽  
Emanuele De Simone ◽  
Giulio Del Vecchio ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Involvement ◽  
Iga Vasculitis ◽  
Adult Onset ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Clinical Records

Abstract Background and Aims IgA-vasculitis (IgAV) is a systemic small vessels vasculitis characterized by deposition of underglycosylated IgA1 immune complexes. Renal involvement indicates severity of illness and chronic kidney disease represents the most serious long-term complication of IgAV. Presently, no treatment is specifically recommended in IgAV Glucocorticoids (GC) have been traditionally thought to be effective in tempering systemic symptoms, but did not show long-term benefits either in reducing flares or progression of kidney disease. The effectiveness of conventional immunosuppressants is controversial. Recently Rituximab (RTX) has been proved to be effective in a few case series of adults with IgAV. However, long term results are lacking. Aim of the study: to evaluate the effectiveness of RTX as first line therapy in induction and maintenance of remission of adults with IgAV with biopsy-proven crescentic glomerulonephritis. Method We reviewed the clinical records of patients with adult-onset IgAV treated with RTX at our Center. Patients included 8 males and 4 females, mean age 45 years (range 19-75) with mean follow-up duration of 31 months (range 6-144). Diagnosis was based on the combination of clinical assessment, serological tests and histological analysis according to EULAR criteria. All patients (pts) had a biopsy proven IgAV- severe nephritis. RTX was given for the treatment of relapsing or refractory disease or because of definite contraindications to standard dose CS and/or conventional immunosuppressants. Patients received 4 weekly doses of RTX (375 mg/m2) given alone (8 pts) or in combination with CS (4 pts). Disease activity was evaluated by Birmingham Vasculitis Activity Score version 3 at the onset and at 1, 6 and 12 months and at the end of follow up. Complete remission (CR) was defined as BVAS of 0 Results Eleven pts (91.7%) achieved a clinical response at 6 months. Ten pts had a CR while 1 pt had a partial response and was given an additional dose of RTX after 12 months from induction due to persistent proteinuria (1gr/24 hrs), despite systemic remission. He achieved a CR 6 months later. One patient did not respond to RTX and was switched to MMF. Among the 10 pts with CR, 1 patient needed maintenance doses of RTX every 6 months due to relapse of palpable purpura; 1 relapsed after 15 months and received a new induction course showing a CR again. Significant decrease in 24-hour proteinuria (P = 0.043), BVAS (P = 0.031),and CRP level from RTX initiation through the last follow-up visit was detected. RTX was generally well tolerated. One patient, who had a CR with RTX alone died after 6 months of follow-up for cardiovascular cause. Conclusion This extended experience confirms our initial results supporting the use of RTX in the treatment of IgAV with severe renal involvement. Indeed, RTX proved to be effective and safe for induction and maintenance of long-lasting remission. Present data also suggest that RTX is not only effective for severe and refractory IgAV, but can be also proposed as a first line therapy.

Renal Involvement and Outcome In Monoclonal Lightchain Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4985-4985
Author(s):  
Raoul Bergner ◽  
Michael J. Uppenkamp ◽  
Martin Hoffmann
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Renal Disease ◽  
Light Chain ◽  
Kidney Biopsy ◽  
Renal Involvement ◽  
The Other ◽  
Renal Outcome ◽  
Al Amyloidosis ◽  
Light Chain Disease

Abstract Abstract 4985 Background: Renal involvement is very common in monoclonal light chain disease (mLCD). However, the types of renal disease are manifold. Also the prognosis and outcome is very different. We analysed the data and renal outcome of patients with monoclonal light chain disease and renal disease. Methods: We analysed the data of patients with monoclonal light chain disease, who underwent a kidney biopsy due to proteinuria and/or renal insufficiency of unclear origin, retrospectively. Data of renal function, proteinuria, the type of renal disease and the renal outcome were collected. The mLCD were subclassified in multiple myeloma (MM), AL-amyloidosis (ALA), monoclonal gammopathy of unclear significance (MGUS) and B-cell non hodgkin lymphona (B-NHL). The kidney biopsy findings were classified in cast nephropathy (CN), ALA, light chain deposit disease (LCDD) and other renal disease (ORD). Results: 88 patients were included in the analysis. 47 patients suffered from MM, 15 from systemic ALA, 21 from MGUS and 5 from B-NHL, respectively. In 17 patients the mLCD was not known before kidney biopsy but detected by typical kidney disease. Of the 47 patients with MM 24 had CN, 4 LCDD, 4 ALA and 15 ORD, respectively. All patients with ALA had renal amyloidosis except one, who had an IgA-glomerulonephritis. All patients with MGUS suffered from ORD only. Patients with B-NHL had CN one patient, LCDD one patient, ALA one patient and ORD two patients, respectively. The ORD were also associated with the mLCD in 21 cases (interstitial nephritis n=7, nephrocalcinosis n=7 and membranoproliferative glomerulonephritis n=4), the other patients had kidney disease independent from mLCD (e.g. diabetic nephropathy, focal segmental glomerulosclerosis, IgA-glomerulonephritits or nephroangiosclerosis). The mean follow up time was 20.4±24.8 month. Patients with CN had a significant worse renal function at time of kidney biopsy [serum creatinine [mg/dl]: CN 4.7±4.0; LCDD 3.36±1.38; ALA 1.46±1.0; ORD 2.0±2.3; p< 0.001 CN vs. ALA and ORD]. Patients with ALA had a significant greater proteinuria [g/d], than the other patients [CN 3.3±2.5; LCDD 1.7±0.9; ALA 5.6±5.2; ORD 2.1±1.9; p< 0.05 ALA vs. LCDD and CN; p<0.001 ORD vs. ALA]. 3.7 months after kidney biopsy 50% of patients with CN were on dialysis (HD). At 12 month 59% of patients with CN were on HD, compared to 37% of patients with ALA, 20% of patients with LCDD and 8% of patients with ORD (p=0.0004). Patients on HD had a significant worse survival compared to those without HD [50% survival 5.3 vs. 42 months; p=0.005]. Discussion: Our data demonstrate, that not all patients with mLCD suffered from a mLCD associated renal disease. The renal prognosis was very different between the types of renal disease. The worst renal outcome had patients with CN followed by patients with ALA. The best renal outcome had patients with ORD. Once on HD the survival is worse than without HD. Based on our data we would recommend to clarify the exact type of renal disease in all patients with mLCD and any evidence of renal disease by kidney biopsy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A multicenter, prospective, observational study to determine association of mesangial C1q deposition with renal outcomes in IgA nephropathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li Tan ◽  
Yi Tang ◽  
Gaiqin Pei ◽  
Zhengxia Zhong ◽  
Jiaxing Tan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Iga Nephropathy ◽  
Cox Regression ◽  
Renal Outcome ◽  
Matched Cohort ◽  
Negative Group ◽  
Renal Survival ◽  
Cox Regression Analysis ◽  
Renal Outcomes

AbstractIt was reported that histopathologic lesions are risk factors for the progression of IgA Nephropathy (IgAN). The aim of this study was to investigate the relationships between mesangial deposition of C1q and renal outcomes in IgAN. 1071 patients with primary IgAN diagnosed by renal biopsy were enrolled in multiple study centers form January 2013 to January 2017. Patients were divided into two groups: C1q-positive and C1q-negative. Using a 1: 4 propensity score matching (PSM) method identifying age, gender, and treatment modality to minimize confounding factors, 580 matched (out of 926) C1q-negative patients were compared with 145 C1q-positive patients to evaluate severity of baseline clinicopathological features and renal outcome. Kaplan–Meier and Cox proportional hazards analyses were performed to determine whether mesangial C1q deposition is associated with renal outcomes in IgAN. During the follow-up period (41.89 ± 22.85 months), 54 (9.31%) patients in the C1q negative group and 23 (15.86%) patients in C1q positive group reached the endpoint (50% decline of eGFR and/or ESRD or death) respectively (p = 0.01) in the matched cohort. Significantly more patients in C1q negative group achieved complete or partial remission during the follow up period (P = 0.003) both before and after PSM. Three, 5 and 7-year renal survival rates in C1q-positive patients were significantly lower than C1q-negative patients in either unmatched cohort or matched cohort (all p < 0.05). Furthermore, multivariate Cox regression analysis showed that independent risk factors influencing renal survival included Scr, urinary protein, T1-T2 lesion and C1q deposition. Mesangial C1q deposition is a predictor of poor renal survival in IgA nephropathy.Trial registration TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074.

MO135THE NEW FIELD OF ONCONEPGROLOGY: EXPERIENCE OF A SINGLE DEDICATED CLINIC

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Chiara Gonzi ◽  
Anna Maria Aschelter ◽  
Francescaromana Festuccia ◽  
Paolo Mene' ◽  
Claudia Fofi
Keyword(s):  
Renal Function ◽  
Renal Disease ◽  
Tyrosine Kinase ◽  
Creatinine Clearance ◽  
Immune Checkpoint ◽  
Renal Injury ◽  
Renal Diseases ◽  
Anti Vegf ◽  
Increased Risk

Abstract Background and Aims The bidirectional relationship between renal disease and malignancy is well known and requires specialized approaches. For this reason, onconephrology has emerged as a new evolving field in the last few years. Method In a dedicated nephrology clinic, we followed 54 metastatic cancer patients (pts) (23 F, 31 M; mean age 68.3 ± 9.8 yrs) during target therapy (TT). They were in treatment for different types of cancer (kidney n=32, colo-rectal n 6=, breast n=5, lung n=5, neuroendocrine n=2 and other n=4).  12 pts were taking anti-VEGF (group 1), 26 pts tyrosine kinase inhib (group 2), 7 pts mTOR inhb (group 3) and 9 pts immune-checkpoint (group 4). Kidney biopsies were not performed because of increased risk or for improvement of RI when changes in TT were performed. Renal injury (RI) occurred on average after 8.9 months from the start of TT. We compared the effects of the different therapeutic interventions on changes of renal function between T0 (before TT) and T1 (during TT). We also documented changes in oncologic therapeutic prescription due to renal injury and their effects at T2 (follow up). Kidney biopsies were not performed because of increased risk or for improvement of RI when changes in TT were performed. A two way repeated measures ANOVA (group x time) was used to compare the effects of the four groups on serum creatinine (sCr), creatinine clearance and proteinuria 24 h (PU) at T0 and T1. Results Mean basal sCr of pts taking antiVEGF was 0.95 mg/dl, eGFR (MDRD) 81.9 ml/min and PU 196 mg 24h. At T1 (8.37 months on average) sCr was 1.74 mg/dl, eGFR 62 ml/min and PU 1777 mg 24h. Mean basal sCr of pts taking tyrosine kinase inhib was 1.24 mg/dl, eGFR 55 ml/min and PU 145 mg 24h. At T1 (13 months on average) sCr was 1.59 mg/dl, eGFR 46 ml/min, and PU 916 mg 24h. Mean basal sCr of pts taking mTOR inhib was 1.28 mg/dl, eGFR 57 ml/min and PU 150 mg 24 h. At T1 (6.3 months on average) sCr was 2.1 mg/dl, eGFR 31.7 ml/min and Pu 345 mg 24 h. Mean basal sCr of pts taking immune-checkpoint was 1.27 mg/dl, eGFR 59 ml/min and PU 150 mg 24h. At T1 (months on average) sCr was 3.74 mg/dl, eGFR 30 ml/min and PU 257 mg 24h. A significant increase in sCr was observed when comparing T0 and T1 among the four groups but only a statistical trend (P = 0.088) was found for the group by time interaction thus not allowing us to speculate on potential differences between the different pharmacological interventions. Lower Creatinine clearance and higher PU, were found at T1 in pts on anti-VEGF compared to those on immune-checkpoint inhibitors. We generally observed an improvement of renal function after reduction of TT dose or its temporary discontinuation (27.8%), but definitive interruption was required in 31.8% of cases. In 2 diabetics pts on tyrosine kinase inhib we observed persistent nephrotic proteinuria and progressive worsening of renal function and beginning of chronic hemodialysis neverthless discontinuation. At the end of follow-up 5 pts reached end-stage renal disease (1 pt was taking antiVEGF, 2 pts tyrosine kinase inhib, 2 immune-checkpoint) and 6 pts were dead (4 pts were taking antiVEGF and 2 pts tyrosin kinasi inhib). Conclusion Our findings suggest that careful monitoring of renal function is needed to optimize the use of TT, also considering that RI can be multifactorial. Onconephrologists work with the aim of trying to ensure the continuity of anti-tumoral therapy, knowing how far they can go to maintain a balance between kidney function (even sacrificing part of it) and patient survival. In conclusion, nephrologists should be increasingly familiar with the diagnosis, management and treatment of renal diseases and the complexity of this field may benefit from well-defined multidisciplinary management by a dedicated team

scholarly journals Long-term Impact of Crystalloid versus Colloid Solutions on Renal Function and Disability-free Survival after Major Abdominal Surgery

2019 ◽  
Vol 130 (2) ◽  
pp. 227-236 ◽  
Author(s):  
Alexandre Joosten ◽  
Amélie Delaporte ◽  
Julien Mortier ◽  
Brigitte Ickx ◽  
Luc Van Obbergh ◽  
...  
Keyword(s):  
Renal Function ◽  
Abdominal Surgery ◽  
Estimated Glomerular Filtration Rate ◽  
Free Survival ◽  
Crystalloid Solution ◽  
Significant Difference ◽  
Goal Directed Fluid Therapy ◽  
Balanced Crystalloid

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background The authors recently demonstrated that administration of balanced hydroxyethyl starch solution as part of intraoperative goal-directed fluid therapy was associated with better short-term outcomes than administration of a balanced crystalloid solution in patients having major open abdominal surgery. In the present study, a 1-yr follow-up of renal and disability outcomes in these patients was performed. Methods All patients enrolled in the earlier study were followed up 1 yr after surgery for renal function and disability using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS). The main outcome measure was the estimated glomerular filtration rate. Other outcomes were serum creatinine, urea, pruritus, and WHODAS score. Groups were compared on a complete-case analysis basis, and modern imputation methods were then used in mixed-model regressions to assess the stability of the findings taking into account the missing data. Results Of the 160 patients enrolled in the original study, follow-up data were obtained for renal function in 129 and for WHODAS score in 114. There were no statistically significant differences in estimated glomerular filtration rate at 1 yr (ml min−1 1.73 m−2): 80 [65 to 92] for crystalloids versus 74 [64 to 94] for colloids; 95% CI [−10 to 7], P = 0.624. However, the WHODAS score (%) was statistically significantly lower in the colloid than in the crystalloid group (2.7 [0 to 12] vs. 7.6 [1.3 to 18]; P = 0.015), and disability-free survival was higher (79% vs. 60%; 95% CI [2 to 39]; P = 0.024). Conclusions In patients undergoing major open abdominal surgery, there was no evidence of a statistically significant difference in long-term renal function between a balanced hydroxyethyl starch and a balanced crystalloid solution used as part of intraoperative goal-directed fluid therapy, although there was only limited power to rule out a clinically significant difference. However, disability-free survival was significantly higher in the colloid than in the crystalloid group.

Follow-Up of Infants With Bilateral Renal Disease Detected In Utero. Growth and Renal Function

1988 ◽  
Vol 140 (6) ◽  
pp. 1607-1607
Author(s):  
V.M. Reznik ◽  
G.W. Kaplan ◽  
J.L. Murphy ◽  
M.G. Packer ◽  
D. Boychuck ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Disease ◽  
In Utero

Cyclophosphamide, Bortezomib and Dexamethasone (CVD) Therapy in AL Amyloidosis Is Associated with High Clonal Response Rates and Prolonged Progression Free Survival,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3978-3978
Author(s):  
Christopher P. Venner ◽  
Julian D Gillmore ◽  
Thirusha Lane ◽  
Darren Foard ◽  
Lisa Rannigan ◽  
...  
Keyword(s):  
Renal Involvement ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Great Promise ◽  
Maximal Response ◽  
Al Amyloidosis ◽  
Effective Treatment Option ◽  
Free Survival ◽  
Entire Cohort

Abstract Abstract 3978 Background: Bortezomib alone and in combination with other agents has shown great promise in the treatment of AL amyloidosis in various preliminary open studies. Here we present our experience at the UK National Amyloidosis Centre with CVD in both the upfront and relapsed setting. Patients and Methods: The primary cohort comprises 37 patients referred to the National Amyloidosis Centre in London from 2006–2010. 27 patients had cardiac involvement by 2005 consensus criteria. 29 had renal involvement, 10 had liver involvement and 26 had other organs involved. Complete information for staging by the Mayo clinic criteria was available in 34 patients, and 47% were stage III based on values obtained prior to the initiation of CVD (23% of upfront patients and 62% of relapsed patients). The recommended CVD regimen was as follows: bortezomib 1.0 mg/m2 IV days 1, 4, 8, 11 (increase to 1.3 mg/m2 if well tolerated) cyclophosphamide 350 mg/m2 po days 1, 8, 15 dexamethasone 20 mg po days 1, 4, 8, 11 (increase to 40 mg if well tolerated) with an aim to deliver 6 cycles of treatment. Dose modifications were at the discretion of the treating haematologist. We aimed to assess response at 6 months (m). Haematologic and organ responses were defined as per the 2005 consensus criteria. The dFLC response (difference between the involved and uninvolved free light chain) was defined as the percent difference in the dFLC at the start of therapy and at response assessment and was considered assessable if the baseline dFLC was >50mg/L. A dFLC of 50–90% defined a partial response, and a dFLC of >90% defined a VGPR. Progression free survival (PFS) was calculated by the Kaplan-Meier method and calculated from the start of CVD until relapse, death or last follow-up. Statistical analysis was performed using SPSS version 19. Approval for analysis and publication was obtained from the institutional review board at the University College London, and written consent was obtained from all patients. Results: Median follow-up was 13.3m. Median time to assessment was 5.9m. Median number of cycles given was 4.9. All 37 patients were assessable by haematologic response criteria, 29 of whom were assessable for dFLC response. Overall hematologic response rate (RR) was 78.4% (CR = 35.1%). A VGPR was attained 48.3% of patients with an overall dFLC RR of 79.3%. 14 patients were treated with CVD upfront with a RR of 85.7% (CR = 64.3%, VGPR = 66.7%). 23 patients were treated in the relapse setting and the RR was 73.9% (CR = 17.4%, VGPR = 35.3%). Clonal response is detailed in table 1. 26 patients were assessable for a BNP response based on a pre-treatment NT-proBNP > 660 ng/L. BNP responses were seen in 8 patients (31%), stable disease in 14 (54%) and progression in 4 (15%). Of the entire cohort only one death was reported and there were no treatment related mortalities. The time to maximal response was 3.8m (3.0m and 3.8m in patients treated upfront and at relapse respectively). Median PFS has not been reached. The estimated 2-year PFS was 55.6% for the entire cohort, 69.6% for patients treated upfront and 43.8% for those treated at relapse. Attaining a CR correlated with a significant improvement in progression free survival compared with those who had not (median PFS not reached vs. 23.1m respectively, P = 0.029; figure 1A). Attaining a VGPR also correlated with an improved PFS compared with those who had not (median PFS not reached vs. 13.2m respectively, P = 0.003; figure 1B). Conclusion: This retrospective series lends further support to the use of bortezomib containing regimens in the treatment of AL amyloidosis. CVD is a safe and effective treatment option supporting similar findings in other small retrospective series, particularly when used in the upfront setting. This is, to our knowledge, the first series reporting PFS with this regimen. In addition, it confirms the importance of achieving a CR for improved survival outcomes and further validates the dFLC response as an important treatment endpoint. CVD is an attractive treatment combination for patients with AL amyloidosis many of whom are transplant ineligible due to advanced disease. Larger phase III studies are warranted and are underway. Disclosures: Wechalekar: Jansen Cilag: Honoraria.

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