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ABSTRACT: AL amyloidosis is caused by a small, indolent plasma cell clone synthesizing light chains that misfold and cause devastating damage of vital organs. Early diagnosis, before development of advanced cardiomyopathy, is the key to improving outcomes. This makes prompt recognition of "red-flags" crucial to trigger appropriate diagnostic procedures. Differentiation from other diagnoses, especially other systemic amyloidoses, may be challenging and may require advanced technologies. Prognosis is heavily dependent on the extent of cardiac involvement, and cardiac biomarkers should guide the choice of therapy. Treatment for AL amyloidosis is highly individualized due to the protean clinical presentation. Close monitoring of clonal and organ response guides regimen changes and duration of therapy. Alkylator-based chemotherapy, either conventional or high-dose, is effective in almost two thirds of patients. The combinations of proteasome inhibitors with dexamethasone and alkylators are feasible in most patients achieving high response rates although there is a need for controlled studies. Risk-adapted stem cell transplant and consolidation with novel agents may be considered in selected patients. The immune-modulatory drugs have an important role in treatment of refractory/relapsed patients. Novel agents and therapeutic targets are expected to be exploited, in the framework of an integrated, more effective and less toxic treatment strategy.
Blood 05/2013; · 9.90 Impact Factor
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ABSTRACT: BACKGROUND: In cardiac AL amyloidosis, myocardial infiltration is typically associated with "low QRS voltages" at the 12-lead electrocardiogram (ECG). Although considered as one of the hallmarks of the disease, its reported prevalence varies from 45% to 70%, mainly because of nonhomogeneous definitions. METHODS: To identify the "low QRS voltage" parameter having the best diagnostic value in identifying cardiac amyloidosis, and to assess its possible prognostic role, ECG and echocardiographic data were collected at diagnosis in 337 consecutive never-treated AL patients (233 with, 104 without cardiac involvement). Prognosis was assessed after a median follow-up of 14.5 months. RESULTS: "Low QRS voltage" prevalence varied from 84.12% when using Sokolow-Lyon index ≤15 mm to 27.04% with the definition of low total voltages (QRS amplitude ≤5 mm in each peripheral and ≤10 mm in each precordial lead), the widely used definition of low peripheral voltages (≤5 mm in each peripheral lead) being able to identify 66.52% cardiac AL patients. The presence of "low peripheral voltages" was associated with a more severe cardiac involvement, and was able to differentiate Mayo stage II patients' survival (i.e., AL patients with intermediate prognosis). According to receiver operator characteristic (ROC) curve analysis, sensitivity and specificity were 58.72% and 80.00%, for a peripheral QRS amplitude ≤24.5 mm (the sum of QRS in all the 6 peripheral leads), and 76.26% and 65.00% for a Sokolow-Lyon index ≤11 mm. CONCLUSIONS: In cardiac AL amyloidosis the prevalence of low QRS voltages is highly dependent on the method used for defining this ECG alteration.
Annals of Noninvasive Electrocardiology 05/2013; 18(3):271-280. · 1.10 Impact Factor
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Ashutosh D Wechalekar,
Stefan O Schonland,
Efstathios Kastritis,
Julian D Gillmore,
Meletios A Dimopoulos,
Thirusha Lane,
Andrea Foli,
Darren Foard,
Paolo Milani,
Lisa Rannigan,
Ute Hegenbart,
Philip N Hawkins,
Giampaolo Merlini, Giovanni Palladini
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ABSTRACT: Key points Deep clonal responses improve outcomes and can change the natural history of advanced (cardiac stage III) AL amyloidosis.NT-proBNP >8500 ng/L and systolic blood pressure <100 mm of Hg identify a very poor risk subgroup of stage III AL amyloidosis.
Blood 03/2013; · 9.90 Impact Factor
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ABSTRACT: Amyloidosis associated with immunoglobulin M clones is a distinct clinical entity that poses specific challenges to clinicians. Although there is substantial overlap, the pattern of organ involvement is peculiar, with higher frequencies of lung, lymph nodes, and peripheral nervous system involvement. Early diagnosis is vital to start effective therapy before irreversible organ damage has occurred and should be based on markers of initial, asymptomatic organ dysfunction, such as natriuretic peptides for heart involvement and albuminuria for renal amyloidosis. Immunoglobulin M clones can give rise to both light chain (AL) and reactive (AA) amyloidosis, and once the diagnosis of amyloidosis is made, correct amyloid typing is necessary to design appropriate therapy and follow-up. Prognostic stratification should include serum albumin concentration, which is an independent prognostic factor.
Clinical lymphoma, myeloma & leukemia 03/2013;
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ABSTRACT: OBJECTIVE: Serum prealbumin has a prognostic value in several diseases, but its serum levels can be influenced by different factors. However, a multivariable analysis to test the independent effect of each has not yet, to our knowledge, been performed. The aim of this cross-sectional study was to investigate the association between prealbumin and several factors possibly affecting its serum levels to test the potential of using prealbumin as an indicator of nutritional status and short-term energy intake in patients newly diagnosed with immunoglobulin light-chain amyloidosis. METHODS: Multivariable general linear regression models of non-collinear variables were fitted to assess the association of demographic (sex, age), nutritional (short-term energy intake, unintentional weight loss, body mass index), and clinical (cardiac and liver involvement, kidney function, C-reactive protein) parameters with serum prealbumin levels in 187 patients newly diagnosed with immunoglobulin light-chain amyloidosis. RESULTS: Serum prealbumin levels were associated with C-reactive protein and short-term energy intake (P < 0.001 for both). A significant association was also detected with age (P = 0.023), serum creatinine (P = 0.017), liver involvement (P = 0.002), and peripheral edema (P = 0.032). In a prespecified subgroup analysis (n = 140) in patients with normal C-reactive protein level (<0.5 mg/dL), all other associations were confirmed. A significant relation was also observed with sex (P = 0.022) and body mass index (P = 0.041). CONCLUSIONS: Serum prealbumin is associated with short-term energy intake independently of the presence of multiple-organ involvement and inflammation. Its serum levels should be always interpreted in light of its influencing factors, among which inflammation and liver and kidney functions appear predominant.
Nutrition 01/2013; · 3.03 Impact Factor
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Giovanni Palladini,
Angela Dispenzieri,
Morie A Gertz,
Shaji Kumar,
Ashutosh Wechalekar,
Philip N Hawkins,
Stefan Schönland,
Ute Hegenbart,
Raymond Comenzo,
Efstathios Kastritis,
Meletios A Dimopoulos,
Arnaud Jaccard,
Catherine Klersy,
Giampaolo Merlini
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ABSTRACT: PURPOSETo identify the criteria for hematologic and cardiac response to treatment in immunoglobulin light chain (AL) amyloidosis based on survival analysis of a large patient population. PATIENTS AND METHODS
We gathered for analysis 816 patients with AL amyloidosis from seven referral centers in the European Union and the United States. A different cohort of 374 patients prospectively evaluated at the Pavia Amyloidosis Research and Treatment Center was used for validation. Data was available for all patients before and 3 and/or 6 months after initiation of first-line therapy. The prognostic relevance of different criteria for hematologic and cardiac response was assessed. RESULTS: amyloid complete response (normal FLC ratio and negative serum and urine immunofixation), very good partial response (difference between involved and uninvolved FLCs [dFLC] < 40 mg/L), partial response (dFLC decrease > 50%), and no response. Cardiac involvement is the major determinant of survival, and changes in cardiac function after therapy can be reliably assessed using the cardiac biomarker N-terminal natriuretic peptide type B (NT-proBNP). Changes in FLC and NT-proBNP predicted survival as early as 3 months after treatment initiation. CONCLUSION
This study identifies and validates new criteria for response to first-line treatment in AL amyloidosis, based on their association with survival in large patient populations, and offers surrogate end points for clinical trials.
Journal of Clinical Oncology 10/2012; · 18.37 Impact Factor
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ABSTRACT: Immune-modulatory drugs are active in immunoglobulin light-chain amyloidosis and the addition of alkylating agents can potentiate their action. In this phase II prospective trial we treated with cyclophosphamide, lenalidomide and dexamethasone 21 patients who were refractory (13, 62%) or relapsed (8, 38%) after prior treatment including melphalan in all cases, bortezomib in 4 and thalidomide in 6. The median number of cycles administered was 4 (range: 2-9 cycles). Severe adverse events were observed in 57% of patients, most common being neutropenia (29%). The hematologic response rate was 62%, with 1 complete response and 5 very good partial responses. Overall median survival was 3 years. The achievement of CR/VGPR was associated with a significant survival advantage. The combination of cyclophosphamide, lenalidomide and dexamethasone is an effective treatment for relapsed/refractory AL amyloidosis, and good quality hematologic response should be the aim of treatment in this setting. (clinicaltrials.gov identifier: NCT00607581).
Haematologica 09/2012; · 6.42 Impact Factor
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Claudio Rapezzi,
Candida Cristina Quarta,
Laura Obici,
Federico Perfetto,
Simone Longhi,
Fabrizio Salvi,
Elena Biagini,
Massimiliano Lorenzini,
Francesco Grigioni,
Ornella Leone,
Francesco Cappelli, Giovanni Palladini,
Paola Rimessi,
Alessandra Ferlini,
Giorgio Arpesella,
Antonio Daniele Pinna,
Giampaolo Merlini,
Stefano Perlini
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ABSTRACT: AimsHereditary transthyretin (TTR)-related amyloidosis (ATTR) is mainly considered a neurologic disease. We assessed the phenotypic and genotypic spectra of ATTR in a Caucasian area and evaluated the prevalence, genetic background, and disease profile of cases with an exclusively cardiac phenotype, highlighting possible hints for the differential diagnosis with hypertrophic cardiomyopathy (HCM) and senile systemic amyloidosis (SSA).Methods and resultsIn this Italian multicentre study, 186 patients with ATTR were characterized at presentation. Thirty patients with SSA and 30 age-gender-matched HCM patients were used for comparison. Phenotype was classified as exclusively cardiac (n = 31, 17%), exclusively neurologic (n = 46, 25%), and mixed cardiac/neurologic (n = 109, 58%). Among the eight different mutations responsible for an exclusively cardiac phenotype, Ile68Leu was the most frequent. Five patients with an exclusively cardiac phenotype developed mild abnormalities at neurological examination, but no symptoms during a 36-month follow-up (range: 14-50). Exclusively cardiac phenotype was characterized by male gender, age >65 years, heart failure symptoms, symmetric left ventricular (LV) 'hypertrophy', and moderately depressed LV ejection fraction. This profile was similar to SSA, but relatively distinct from HCM. Compared with patients with a mixed phenotype, patients with an exclusively cardiac phenotype showed a more pronounced cardiac involvement on both echocardiogram and electrocardiogram (ECG).ConclusionA clinically relevant subset of Caucasian ATTR patients present with an exclusively cardiac phenotype, mimicking HCM or SSA. Echocardiographic and ECG findings are useful to differentiate ATTR from HCM but not from SSA. The role of liver transplantation in these patients should be reconsidered.
European Heart Journal 06/2012; · 10.48 Impact Factor
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Stefano Perlini,
Francesco Salinaro,
Francesco Cappelli,
Federico Perfetto,
Franco Bergesio,
Alessio Alogna,
Roberta Mussinelli,
Michele Boldrini,
Ambra Raimondi,
Francesco Musca, Giovanni Palladini,
Giampaolo Merlini
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ABSTRACT: BACKGROUND: In light-chain (AL) cardiac amyloidosis, the 12-lead electrocardiogram (ECG) reflects myocardial amyloid infiltration with low limb voltages, pseudoinfarction patterns, and conduction abnormalities. Moreover, it is not unusual to see "aspecific" QRS complex abnormalities, such as notches and RsR' pattern in the absence of QRS prolongation, i.e. a fragmentation of QRS complexes (fQRS), that has been associated with myocardial scars and prognosis. Since cardiomyocyte damage and interstitial fibrosis are associated with cardiac amyloid deposition, aim of the present study was to analyze the prevalence and the potential prognostic value of fQRS in patients with cardiac amyloidosis. METHODS: We enrolled 375 consecutive untreated patients in whom a first AL amyloidosis diagnosis was concluded between 2008 and 2010, 264 with and 111 without heart involvement. Patients with a positive history of coronary disease were excluded from the analysis. RESULTS: The prevalence of fQRS was significantly higher in patients with cardiac AL amyloidosis (28.5% vs. 11.7%; p=0.0008). After a median follow-up of 561days, Kaplan-Meier survival analysis revealed a significantly higher mortality in the fQRS group when compared with the "normal" QRS group (p=0.0008). No association was found between the presence of fQRS and the duration of PQ, QRS, and QTc intervals, the presence of peripheral low voltages or pseudonecrosis, NT-proBNP serum levels or cardiac wall thickness. CONCLUSIONS: In patients with cardiac AL amyloidosis, the presence of fQRS at diagnosis has an independent prognostic value. Such a simple and cheap analysis in patients' diagnostic work-up may improve diagnosis and prognostic stratification.
International journal of cardiology 06/2012; · 7.08 Impact Factor
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ABSTRACT: In AL amyloidosis prognosis depends on the severity of heart dysfunction which is best assessed by natriuretic peptides (BNP and NT-proBNP). However, their clearance relies on glomerular filtration rate (GFR) and their concentration increases with renal failure. We evaluated the diagnostic and prognostic performance of NT-proBNP and BNP in 248 patients with AL amyloidosis with different degrees of renal failure. Patients were grouped according to GFR. Group 1 comprised 109 patients with GFR ≥60 mL/min/1.73 m(2) , Group 2, 77 subjects with GFR <60 and ≥15 mL/min/1.73 m(2) , and Group 3, 62 patients with GFR <15 mL/min/1.73 m(2) . The ability of natriuretic peptides to detect heart involvement and to predict survival in the three groups was assessed. Decreasing eGFR required higher cutoffs of both NT-proBNP and BNP for detecting heart involvement and predicting survival. Both natriuretic peptides were independent prognostic markers in Groups 1 and 2, whereas in Group 3 only BNP independently predicted survival. Natriuretic peptides are powerful and useful markers of cardiac dysfunction and prognosis, provided that eGFR is considered in interpreting their clinical meaning. BNP should be preferred in patients with end-stage renal failure.
American Journal of Hematology 01/2012; 87(5):465-71. · 4.67 Impact Factor
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ABSTRACT: The cardiac involvement and associated mortality that occur in systemic AL amyloidosis remain among the most challenging aspects of the systemic amyloid-related diseases. Monoclonal immunoglobulin light chains produced by a clone of plasma cells are usually the cause of symptoms and organ dysfunction via both poorly understood toxic effects of misfolded species and accumulation of interstitial amyloid fibrils in key viscera. Treatment is aimed at eliminating the clonal cells in order to eliminate toxic light chain production. Recent advances in therapy have helped many patients with AL achieve complete hematologic responses and significant reversal of organ damage but these benefits do not extend to that 10-15 % who present with advanced cardiac involvement. Even with cardiac transplant followed by effective therapy such as stem cell transplant, outcomes for these patients remain promising at best.
Sub-cellular biochemistry 01/2012; 65:609-42.
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ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic plasma cell disorder occurring in 4.2% of adults > 50 years of age, which can progress into symptomatic diseases either through proliferation of the plasma cell clone, giving rise to multiple myeloma and other lymphoplasmacellular neoplasms, or through organ damage caused by the monoclonal protein, as seen in light-chain amyloidosis and related conditions. Differential diagnosis of asymptomatic and symptomatic monoclonal gammopathies is the determinant for starting therapy. The criteria for determining end-organ damage should include markers of organ injury caused by the monoclonal protein. Patient assessment and optimal follow-up are now performed using risk stratification models that should also take into account the risk of developing AL amyloidosis. Patients with low-risk MGUS (approximately 40% of all MGUS patients) need limited assessment and very infrequent follow-up. The ongoing development of novel molecular biomarkers and advanced imaging techniques will improve the identification of high-risk patients who may benefit from early therapeutic intervention through innovative clinical trials.
Hematology 01/2012; 2012:595-603. · 1.49 Impact Factor
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ABSTRACT: Serial measurement of NT-proBNP is performed routinely in the monitoring and assessment of the effectiveness of therapy in patients being treated for chronic heart failure (CHF). Intra-individual changes in NT-proBNP levels over time are compared typically to a reference change value (RCV) determined using either a standard [i.e., nested analysis of variance (nANOVA)] or a lognormal approach. The RCV defines the minimum percent change in serial analyte values that exceeds the percent change expected due to biological variation alone. Currently, there is no consensus on which approach (nANOVA or lognormal) to determining RCV is better.
Based on these considerations, we aimed to illustrate the impact of data transformation on the calculation of the biological variation of NT-proBNP and discuss the utility of logarithmic transformation in monitoring patients with heart failure.
15 healthy subjects were enrolled after informed consent; 5 blood specimens were collected twice a week. Nested ANOVA from replicate analyses was applied to obtain components of biological variation, on the raw data and after data transformation.
NT-proBNP distribution being highly skewed required data transformation. Natural log transformation yielded normalization. An example demonstrates that for untransformed values the RCV was overestimated for low concentrations of NT-proBNP and underestimated for higher concentrations.
Log-transformed data are often used in the establishment of reference intervals for evaluating laboratory tests results in clinical practice, especially when the reference interval data are not Gaussian distributed. As log-normal approach is the best approach to determining RCV values we encourage its use assessing the clinical utility of NT-proBNP serial testing. We propose that the log-normal approach becomes the standard approach to determining RCV and replaces the use of nANOVA.
Clinica chimica acta; international journal of clinical chemistry 12/2011; 413(5-6):544-7. · 2.54 Impact Factor
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Giovanni Palladini,
Alessandra Barassi,
Stefano Perlini,
Paolo Milani,
Andrea Foli,
Paola Russo,
Riccardo Albertini,
Laura Obici,
Francesca Lavatelli,
Gabriele Sarais,
Simona Casarini,
Remigio Moratti,
Gian Vico Melzi d'Eril,
Giampaolo Merlini
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ABSTRACT: Cardiac biomarkers play a major role in the identification of patients at risk of early death in AL amyloidosis, and a staging system based on amino-terminal pro-natriuretic peptide type-B (NT-proBNP) and troponins (cTn) is used for prognostic stratification. Adrenomedullin is produced by several tissues including the heart, and portends a poor prognosis in heart diseases. We investigated the ability of midregional proadrenomedullin (MR-proADM) to predict early death in AL amyloidosis.
One-hundred and thirty consecutive patients with newly-diagnosed AL amyloidosis were prospectively enrolled. The impact on survival of NT-proBNP, cTnI and MR-proADM was evaluated.
The concentration of MR-proADM correlated with systolic and diastolic function, but did not reflect the amount of amyloid deposited in the heart. Moreover, MR-proADM was associated with non-cardiac markers of advanced disease. The staging system based on NT-proBNP and cTnI identified high-risk subjects, but could not discriminate good-risk and intermediate-risk patients. Conversely, a staging system based on MR-proADM and cTnI identified 3 groups with significantly different survivals.
Midregional-proADM is a powerful prognostic marker in AL amyloidosis, which may not only reflect cardiac dysfunction but also widespread systemic disease, and can be combined with cTn for detecting patients at risk of early death.
Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 11/2011; 18(4):216-21. · 2.12 Impact Factor
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ABSTRACT: Monoclonal Ig light chains (LC) can be responsible for pathologic conditions in humans, as in systemic amyloid light amyloidosis. Protean clinical manifestations characterize this disorder with the most varied combination of symptoms generated by different degrees of diverse organ involvement. Kidney and heart are most frequently interested, with major heart involvement as the most relevant prognostic factor. The identification of the underlying mechanism involved in organ targeting is of major relevance for the pathobiology of this disorder. To this aim, we characterized the repertoire of variable region germline genes of λ LC preferentially targeting the heart and compared it with the repertoire of LC that do not in a case-control study. We found that the repertoires were highly restricted, showing preferential use of the same few germline genes but with a different frequency pattern. A single gene, IGVL1-44, was found associated with a 5-fold increase in the odds of dominant heart involvement (after adjusting for confounders in a multivariable logistic model). These results support an involvement of LC genetics in the determination of organ targeting. Study of the characteristics of IGVL1-44-LC with, and of the minority without, heart involvement might lead to identification of LC/tissue interactions.
Blood 11/2011; 119(1):144-50. · 9.90 Impact Factor
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ABSTRACT: Considering the important advances in treating specific types of systemic amyloidoses, unequivocal typing of amyloid deposits is now essential. Subcutaneous abdominal fat aspiration is the easiest, most common diagnostic procedure. We developed a novel, automated approach, based on Multidimensional Protein Identification Technology, for typing amyloidosis. Fat aspirates were obtained from patients with the most common systemic amyloidoses (ALλ, ALκ, transthyretin, and reactive amyloidosis), with Congo red score more than or equal to 3+, and nonaffected controls. Peptides from extracted and digested proteins were analyzed by Multidimensional Protein Identification Technology. On semiquantitative differential analysis (patients vs controls) of mass spectrometry data, specific proteins up-represented in patients were identified and used as deposit biomarkers. An algorithm was developed to classify patients according to type and abundance of amyloidogenic proteins in samples; in all cases, proteomic characterization was concordant with fibril identification by immunoelectron microscopy and consistent with clinical presentation. Our approach allows reliable amyloid classification using readily available fat aspirates.
Blood 09/2011; 119(8):1844-7. · 9.90 Impact Factor
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Riccardo Caccialanza, Giovanni Palladini,
Catherine Klersy,
Emanuele Cereda,
Chiara Bonardi,
Barbara Cameletti,
Elisabetta Montagna,
Paola Russo,
Andrea Foli,
Paolo Milani,
Francesca Lavatelli,
Giampaolo Merlini
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ABSTRACT: Nutritional status is an independent prognostic factor in immunoglobulin light-chain amyloidosis (AL), but its influence on quality of life (QoL) is unknown. The aim of this cross-sectional study was to investigate the association between nutritional status and QoL in AL patients at diagnosis. One hundred and fifty consecutive patients with biopsy-proven AL were assessed for nutritional status by anthropometry [body mass index, unintentional weight loss (WL) in the previous 6 months and mid-arm muscle circumference (MAMC)], biochemistry (serum prealbumin), and semiquantitative food intake at referral. QoL was assessed by the Medical Outcomes Study 36-item Short Form General Health Survey. The composite physical component summary (PCS) and the mental component summary (MCS) for AL outpatients were 36.2 ± 10.1 and 44.9 ± 11.3, respectively (p < 0.001 for both vs the population norms of 50). In multivariate linear regression models adjusted for gender, age, Eastern Cooperative Oncology Group performance status, the number of organs involved, the severity of cardiac damage, C-reactive protein, energy intake, and WL, PCS was significantly lower for serum prealbumin <200 mg/L and MAMC <10th percentile (adjusted difference 3.8, 95% CI 0.18-7.5, p = 0.040 and 5.3, 95% CI 2.0-8.7, p = 0.002, respectively). MCS was decreased by 0.47 (95% CI 0.18-0.75, p = 0.002) for each kilogram of body weight lost in the previous 6 months. Nutritional status independently affects QoL in AL patients since diagnosis. Nutritional evaluation should be integral part of the clinical assessment of AL patients. Nutritional support intervention trials are warranted in such patients' population.
Annals of Hematology 08/2011; 91(3):399-406. · 2.62 Impact Factor
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Oncology (Williston Park, N.Y.) 06/2011; 25(7):633, 637-8. · 1.03 Impact Factor
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Donna E Reece,
Ute Hegenbart,
Vaishali Sanchorawala,
Giampaolo Merlini, Giovanni Palladini,
Joan Bladé,
Jean-Paul Fermand,
Hani Hassoun,
Leonard Heffner,
Robert A Vescio,
Kevin Liu,
Christopher Enny,
Dixie-Lee Esseltine,
Helgi van de Velde,
Andrew Cakana,
Raymond L Comenzo
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ABSTRACT: This first prospective phase 2 study of single-agent bortezomib in relapsed primary systemic AL amyloidosis evaluated the recommended (maximum planned) doses identified in phase 1 testing (1.6 mg/m² once weekly [days 1, 8, 15, and 22; 35-day cycles]; 1.3 mg/m² twice weekly [days 1, 4, 8, and 11; 21-day cycles]). Among all 70 patients enrolled in the study, 44% had ≥ 3 organs involved, including 73% and 56% with renal and cardiac involvement. In the 1.6 mg/m² once-weekly and 1.3 mg/m² twice-weekly groups, the hematologic response rate was 68.8% and 66.7% (37.5% and 24.2% complete responses, respectively); median time to first/best response was 2.1/3.2 and 0.7/1.2 months, and 78.8% and 75.5% had response durations of ≥ 1 year, respectively. One-year hematologic progression-free rates were 72.2% and 74.6%, and 1-year survival rates were 93.8% and 84.0%, respectively. Outcomes appeared similar in patients with cardiac involvement. Among all 70 patients, organ responses included 29% renal and 13% cardiac responses. Rates of grade ≥ 3 toxicities (79% vs 50%) and discontinuations/dose reductions (38%/53% vs 28%/22%) resulting from toxicities appeared higher with 1.3 mg/m² twice-weekly versus 1.6 mg/m² once-weekly dosing. Both bortezomib dose schedules represent active, well-tolerated regimens in relapsed AL amyloidosis. This study was registered at www.clinicaltrials.gov as #NCT00298766.
Blood 05/2011; 118(4):865-73. · 9.90 Impact Factor
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ABSTRACT: The increasing number of effective agents allows rescue therapy of patients with light-chain (AL) amyloidosis refractory to ≥2 previous treatments. Lenalidomide is effective in this disease and its toxicity profile encourages its use in salvage regimens. All the patients with AL amyloidosis refractory to both melphalan and bortezomib referred to our center between July 2007 and July 2009 were treated with the combination of lenalidomide and dexamethasone. Twenty-four consecutive patients were enrolled. Seventy-nine percent were also refractory to thalidomide. Two patients died before evaluation of response, and 50% experienced severe adverse events. Survival was significantly shorter in subjects with troponin I >0.1 ng/mL and in patients diagnosed <18 months before treatment initiation. Hematologic response was observed in 41% of patients and prolonged survival (median 10 months vs. not reached, P = 0.005) independently from troponin I concentration and from pre-treatment disease duration. Salvage therapy beyond second line of treatment can improve survival in AL amyloidosis and lenalidomide plus dexamethasone is a valuable option in this setting.
Annals of Hematology 04/2011; 91(1):89-92. · 2.62 Impact Factor
