Treatment of Light Chain (AL) Amyloidosis and Light Chain Deposition Disease (LCDD) with the Combination of Bortezomib and Dexamethasone.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 191-191 ◽  
Author(s):  
Efstathios Kastritis ◽  
Athanasios Anagnostopoulos ◽  
Maria Roussou ◽  
Savvas Toumanidis ◽  
Constantinos Pamboukas ◽  
...  
Keyword(s):  
Median Time ◽  
Light Chain ◽  
Dose Adjustment ◽  
High Dose ◽  
Al Amyloidosis ◽  
Light Chain Deposition Disease ◽  
Hematologic Response ◽  
Organ Response ◽  
Light Chain Deposition

Abstract Background: Primary (AL) amyloidosis and light chain deposition disease (LCDD) are clonal plasma cells disorders characterized by deposition of either amyloid fibrils (in AL) or amorphous nodular non-congophilic deposits (in LCDD) derived from abnormal light chains, that cause failure of affected organs. Treatment of AL is based on steroids and standard dose or high dose melphalan with ASCT. Data on treatment of LCDD are limited. Bortezomib, a proteasome inhibitor, has significant activity in myeloma, which is enhanced by the addition of dexamethasone (BD) and can be given in myeloma patients with renal impairment. We evaluated this combination in patients with AL and LCDD. Methods: We treated consecutive patients with AL or LCDD with the combination of Bortezomib (1.3 mg/m2 days 1, 4, 8 and 11) and Dexamethasone (40 mg days 1–4), every 21 days, for up to 6 cycles. Dose modifications were made based on toxicity. Organ involvement and hematologic and organ response were assessed following standard criteria (Gertz et al, Am J Hematol 2005). Results: Since September 2005, 21 consecutive AL and 2 LCDD patients started treatment with BD. Eight patients (38%) had at least one prior therapy and 13 (62%) had ≥2 organs involved; kidneys and heart were affected in most patients. The majority had impaired performance status, high BNP values and 7 (33%) patients had creatinine>2 mg/dl. Among the 21 AL patients, 2 are early for evaluation, 4 had non-measurable disease and 15 patients are evaluable: 13 (87%) responded (CR+PR) and 7 (47%) achieved hematologic CR. All 5 patients refractory to high dose DEXA had a hematologic response and 3 had a CR. Two of 3 AL patients with abnormal FLC ratio but involved FLC<100 mg/L achieved normal FLC ratio. Both patients with LCDD responded- the patient who was refractory to VAD had a CR. Median time to hematologic response was 0.93 months; all responses occurred within 2 courses while all patients in hematologic CR maintain CR for a median of 10.5 months (range 4.6–21). So far, 6 (28%) AL patients had organ responses (3 renal and 3 cardiac) while 7 (44%) patients had a sustained >50% reduction in BNP. Median time to organ response in AL patients was 4 months (range 2–8). In both LCDD patients albuminuria was reduced by more than 50%. Median follow-up for all patients and for living patients is 9.5 months (range 1–23) and 12 months (range 4–23) respectively. In an intention to treat basis 8 (38%) patients have progressed, including 3 AL patients (14%) who died while on treatment (with two of them at hematologic PR at the time of their death- one died before she was assessable for response). Five AL patients had either hematologic or organ progression at a median of 6.8 months after treatment initiation. Peripheral neuropathy, fatigue, peripheral edema, constipation and exacerbation of postural hypotension were managed with appropriate dose adjustment; however 10 (47%) patients were not able to receive the planned 6 courses. Conclusions: The combination of BD is feasible for patients with AL amyloidosis and LCDD. Most patients achieve rapid hematologic response and toxicity can be managed with close follow-up and appropriate dose adjustment. This treatment may be a valid option for patients with severe heart or kidney impairment who are not candidates for other therapies.

High Dose Melphalan with Autologous Stem Cell Transplantation Overcomes Poor Prognosis of Primary Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1350-1350
Author(s):  
Simrit Parmar ◽  
Mubeen Khan ◽  
Gabriela Rondon ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Plasma Cells ◽  
High Dose ◽  
Al Amyloidosis ◽  
Hematologic Response ◽  
Bone Marrow Plasma ◽  
Organ Response ◽  
High Dose Melphalan

Abstract Abstract 1350 Background: Systemic Primary AL Amyloidosis is a rare but potentially fatal disease resulting from tissue deposits of amyloid fibrils derived from monoclonal immunoglobulin light chains. High-dose melphalan followed by autologous hematopoietic stem cell transplant (auto HCT) is associated with hematologic and organ responses and improved survival. Methods: In this retrospective analysis we identified 46 patients with primary AL amyloidosis who received auto HCT between 01/1998 to 05/2010 at MDACC. Organ responses were determined using Amyloidosis Consensus Criteria. Results: The median age at auto HSCT was 56 years (34-74) where 61% were males and 35% were older than 60 years of age. 61% had lambda light chain restriction and only 4% had cytogenetic abnormalities. Disease characteristics are summarized in Table 1. The median time from diagnosis to auto HCT was 6.6 months (2.2-29.4 months). 22 pts (47.8%) had one organ, 19 pts (41.3%) had 2 organ and 4 pts (8.7%) had 3 organ involvement. 11 pts (23.9%) had heart and 35 pts (76.1%) had kidney involvement. The median follow up from the time of diagnosis was 22.4 months and from time of auto HCT was 16.7 months. High dose Melphalan dose was 200mg/m2 in 24 pts (52%) and 140mg/m2 in 22 (47.8%). There were 4 early deaths and 4 pts whose follow up was less than 3 months and their response was not assessed. Out of the 38 evaluable patients, the post-transplant organ responses were as follows ≥PR 25(66%), ≥stable disease 35(92%) (Table2). The hematologic responses were: CR=5 (13%), ≥VGPR=10(26%), ≥PR=26 (68%), ≥SD=37(97%). One patient had progressive disease. There was a correlation between organ response and hematologic response (chi square;p<10-3). The day-100 treatment related mortality (TRM) was 8.7% and 1-yr TRM was 13%. The median progression-free (PFS) and overall survival (OS) from auto HCT was 73.8 months and not reached (from transplant). The median PFS and OS from diagnosis were 93 months and 59.8 months respectively. In multivariate analysis, heart involvement (p=0.01), female sex (p=0.011), age ≥60 years (p=0.002), bone marrow plasma cells≥10% (p=0.043) and Beta-2 microglobulin>3.5mg/l (p=0.02) were associated with poor OS. Improved OS correlated with organ response (52.6 vs 11.4 months; p=0.01) and hematologic response (52.6 vs.6.1months; p=0.002). Hemoglobin <10 g/dl (p=0.047), bone marrow plasma cells≥10% (p=0.043) and age≥60 years (p=0.075) were associated with shorter PFS. Hematologc response (p=0.48) and organ response (p=0.12) were not associated with improved PFS. Conclusion: In this analysis the outcome of patients with primary systemic AL amyloidosis was durable with auto HCT with acceptable mortality risk and improved survival. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Firstline Daratumumab Shows High Hematologic and Organ Response Rates in Advanced Cardiac AL Amyloidosis - a Retrospective Case Series

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3123-3123
Author(s):  
Georg Jeryczynski ◽  
Antonia Eder ◽  
Eva-Maria Reitter ◽  
Maria-Theresa Krauth ◽  
Hermine Agis
Keyword(s):  
High Risk ◽  
Median Time ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Stage Iiia ◽  
Hematologic Response ◽  
Risk Patients ◽  
Organ Response ◽  
Very High

Background AL amyloidosis is a plasma cell dyscrasia and the most common form of amyloidosis. It is associated with deposition of light chain amyloid, which leads to organ dysfunction, most commonly of the heart and kidneys. Treatment focuses on the reduction of the production of the monoclonal light chains and includes the off-label use of antimyeloma drugs. Their use, however, is often limited by the advanced organ dysfunction frequently encountered in these patients. Daratumumab, a monoclonal CD38 antibody has shown efficacy in both newly diagnosed and relapsed AL amyloidosis in several reports. It is usually well tolerated in patients with advanced AL amyloidosis-related heart failure and requires no dose adjustment for impaired kidney function. Aims and Methods The aim of this study was to retrospectively assess the efficacy of daratumumab in a single-center cohort of newly diagnosed AL amyloidosis patients. A chart review was performed on all patients treated with frontline daratumumab as an individual healing attempt at the Department of Oncology at the Medical University of Vienna between April 2017 and May 2019. Results A total of 14 patients (nine male, five female) were evaluable. According to the 2004 Mayo staging system one patient was stage I, four patients were stage II and nine patients were stage III, two of which were in the very high risk group IIIb (NT-proBNP > 8500 ng/L). Twelve patients produced monoclonal lambda light chains. Median number of organs involved was 2 (1-4), with heart (78.6%) and kidneys (64.3%) being the most common. All patients received daratumumab at the dose of 16 mg/m2 for at least 3 cycles (range 3-19). Dexamethasone was reduced to 20 mg per daratumumab infusion to increase tolerability. After a median follow-up of 12.5 months (range 2.17-25.17), eleven patients were still receiving daratumumab at time of analysis. One patient with stage IIIa proceeded to heart transplant after four cycles and later underwent autologous stem cell transplantation, while two patients were lost to follow-up (one patient had to withdraw from treatment due to psychiatric comorbidities; one patient moved to a different center). Seven patients were treated with daratumumab alone, seven patients received either additional proteasome inhibitors, additional IMIDs, or both during the course of their treatment. One patient was also briefly treated with oral cyclophosphamide. Two patients experienced infusion reaction at first administration. There was no severe toxicity leading to discontinuation observed, the most significant toxicity was susceptibility to infections for which six patients received intravenous immunoglobulins. Hematologic and organ response were assessed using previously published criteria (Comenzo et al 2012). All patients showed hematologic response at last follow-up. First hematologic response was classified as PR in 50% and VGPR in 50% after a median time of 44 days (7-252). Best hematologic response was VGPR in 78.6% and CR in 21.4%. The rates remained the same to last follow-up. Median time to best response was 277 days (14-412). In the group of high and very high risk patients 77.8% achieved VGPR and two stage IIIa patients (22.2%) achieved CR at last follow-up. Cardiac response was seen in five out of eleven evaluable patients, all classified as stage IIIa, while kidney response was seen in three out of nine (33.3%) patients with kidney involvement. Median time to heart and kidney response was 281 (88-348) and 196 (62-215) days respectively. Conclusion Daratumumab showed high efficacy as a firstline treatment in newly diagnosed AL amyloidosis yielding a 100% objective hematologic response rate and a significant organ response rate even in high risk patients that usually have a very poor prognosis and limited treatment options. Despite the limitations inherent to any retrospective study, our data underline the role of daratumumab as a safe, effective, and tolerable treatment option in AL amyloidosis both as a monotherapy as well as a combination partner for other agents, in particular in patients with advanced stage AL amyloidosis. Figure OffLabel Disclosure: Off-label use of daratumumab in AL Amyloidosis as an individual healing attempt

scholarly journals Light Chain Deposition Disease: First Analysis of an International Study in 359 Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Paolo Milani ◽  
Nelson Leung ◽  
Efstathios Kastritis ◽  
Stefan Schönland ◽  
Ute Hegenbart ◽  
...  
Keyword(s):  
Light Chain ◽  
Research Funding ◽  
Univariate Analysis ◽  
Response Criteria ◽  
Al Amyloidosis ◽  
Light Chain Deposition Disease ◽  
Hematologic Response ◽  
Bone Marrow Plasma ◽  
Light Chain Deposition ◽  
Serum And Urine

Introduction: Light chain deposition disease (LCDD) is a rare complication of monoclonal gammopathies, defined by non-amyloid linear monoclonal light chain (most commonly kappa) deposits in the kidney and other organs. The rarity of LCDD has hampered clinical studies and staging systems and response criteria are lacking. The International Kidney Myeloma Working Group (IKMG) started a clinical data collection from all participating centers in order to define the natural history of LCDD, and to establish prognostic factors and response criteria in a large, international, unselected patient population. Methods: Eight referral centers have yet participated in the data collection at the data lock of July 31, 2020. Patient inclusion is ongoing and expected accrual is 500 patients. The diagnosis of LCDD had to be biopsy-proven. The patients were diagnosed between 1992 to 2020. Response was assessed 6 months after treatment initiation according to the criteria used in light chain (AL) amyloidosis. Renal survival (RS) was defined as time from diagnosis to dialysis or last follow-up. Patients who died without requiring dialysis were censored at the time of death. The analysis of factors predicting RS was performed in patients whose baseline estimated glomerular filtration rate (eGFR) was &gt;15 mL/min. The cutoffs of baseline variables, as well as the cutoffs measured at the time of response, best predicting RS or OS at 12 months were identified by means of Receiver Operator Characteristics (ROC) analyses. All patients gave written informed consent for their clinical data to be used for research purposes. Results: Overall, 359 patients have been included in this first analysis. Sixteen (4%) subjects had concomitant cast nephropathy. The main clinical characteristics are reported in the Table. Median overall survival (OS) was 13 years and RS was 12 years (Figure1 A and 1B) and median survival of living patients is 4.5 years. At univariate analysis the only baseline variables predicting RS were proteinuria [best cutoff 2.5 g/24h, HR 2.25 (95%CI 1.13-4.60), P=0.02], and eGFR [best cutoff &gt;30 mL/min, HR 0.50 (95%CI 0.26-0.96) P=0.037], but at multivariate analysis only proteinuria predicted RS [HR 2.17 (95% CI 1.08, 4.33), P=0.027]. At univariate analysis, a higher bone marrow plasma cell infiltrate (best cutoff ≥20%) at diagnosis was associated with a significantly lower OS [HR 1.96 (95% CI 1.23-3.13) P=0.004], as was having end stage renal disease (ESRD) defined as an eGFR &lt;15 mL/min [HR 1.81 (95%CI 1.11-2.92) P=0.015]. We then tested the ability of the hematologic response criteria for AL amyloidosis to discriminate groups with different survival after treatment in a 6 months landmark analysis. Our choice of adopting the amyloidosis response criteria was corroborated by the results of the ROC analysis showing that the difference between involved and uninvolved free light chains (dFLC) cutoff (40 mg/L) used in AL amyloidosis to define very good partial response (VGPR) had 87% sensitivity and 65% specificity in identifying patients who needed dialysis within 12 months. Partial response (PR, 19% requiring dialysis at 3 years) was not associated with a RS benefit over no-response (29% requiring dialysis at 3 years, P=0.511). However, VGPR conferred a significant RS advantage (10% requiring dialysis at 3 years) over PR (P=0.002). No significant difference in RS was seen between complete response (CR, 0% requiring dialysis at 3 years) and VGPR (P=0.178). Thus, achieving VGPR or CR by amyloidosis response criteria [post-treatment dFLC&lt;40 mg/L (VGPR by AL criteria), with or without negative serum and urine immunofixation and normal FLC-ratio (CR by AL criteria)] was adopted as a provisional criterion for hematologic response in LCDD (Figure 1D). LCDD response was also associated with prolonged OS (Figure 1C). Conclusions: Almost one-third of patients with LCDD are diagnosed when they already have ESRD resulting in shorter OS. The degree of proteinuria and of bone marrow plasma cell infiltration predict RS and OS, respectively. Achievement of post treatment dFLC &lt;40 mg/L or negative serum and urine immunofixation at 6 months is proposed as a provisional criterion for hematologic response, being able to predict both improved RS and OS. Planned expanded recruitment might allow a validation analysis of the results, the analysis of organ response data and the evaluation of different time-points for response assessment. Disclosures Milani: Celgene: Other: Travel support; Janssen: Other: Speaker honoraria; Pfizer: Other: Speaker honoraria. Kastritis:Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria. Schönland:Janssen, Prothena, Takeda: Honoraria, Other: travel support to meetings, Research Funding. Bridoux:Baxter: Consultancy; Janssen: Honoraria; Celgene: Honoraria. Tuchman:Celgene: Honoraria, Research Funding, Speakers Bureau; Oncopeptides: Consultancy; Amgen: Research Funding; Caelum: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Research Funding; Roche: Research Funding; Karyopharm: Honoraria, Research Funding. Jimenez-Zepeda:Janssen, Celgene, Amgen, Takeda: Honoraria. Palladini:Jannsen Cilag: Honoraria, Other; Celgene: Other: Travel support. Wechalekar:Celgene: Honoraria; Caelum: Other: Advisory; Janssen: Honoraria, Other: Advisory; Takeda: Honoraria, Other: Travel.

scholarly journals P1693LONG-TERM OUTCOME OF KIDNEY TRANSPLANTATION IN PLASMA CELLS DYSCRASIAS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Fulvia Zappulo ◽  
Gabriele Donati ◽  
Giorgia Comai ◽  
Claudia Bini ◽  
Andrea Angeletti ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Light Chain ◽  
Graft Failure ◽  
Case Series ◽  
University Hospital ◽  
High Dose ◽  
Light Chain Deposition Disease ◽  
Light Chain Amyloidosis ◽  
First Case

Abstract Background and Aims Survival of patients with Multiple Myeloma (MM), Light Chain Amyloidosis (LCA) and Monoclonal Gammopathies of renal significance (MGRS) on chronic renal replacement therapy (RRT) is poor. The gold standand treatment of plasma cell dyscrasias (PCD) is high-dose chemotherapy followed by Autologous Stem Cell Transplantation (ASCT) which can induce complete remission and longer survival than chemotherapy alone. Kidney transplantation (KT) after ASCT could represent an option for patients with PCD and End Stage Renal Disease (ESRD). There is no evidence about the time of follow up required from MM remission and KT. Method We present a case series of 5 patients who underwent KT after ASCT and remission of MM among 2,500 transplant recipients followed at the Nephrology Dialysis and Renal Transplantation Unit of S.Orsola University Hospital from 1967 untill now. As in case of recovery from solid cancers, the feasibility of KT after MM was considered when no signs of relapse were assessed. In our cohort 3 patients were affected by Light Chain Deposition Disease (LCDD), 1 patient presented Myeloma Cast Nephropathy (MCN) and one patient Light Chain Amyloidosis (LCA). They all required RRT and underwent KT after ASCT. Results Time between ASCT and KT ranged from 3 and 11 years and clinical outcome was very different. The mean follow up period ranged from 2 to 4 years. In the first case (LCDD) KT was performed 11 years after ASCT, the graft failure occurred 6 years later because of chronic allograft nephropathy requiring RRT. In the second case (LCDD) patient received KT 3 years after ASCT. He developed Bence-Jones proteinuria requiring specific therapy with Dexametasone and Bortezomib determining progressive graft failure. In the third case (LCDD) KT was performed 4 years after ASCT and the 4 year follow up is negative for relapse of MM or ESRD. The fourth patient presented MCN and received KT 8 years after ASCT. MCN relapsed 6 years later; it caused ESRD requiring RRT. In the last patient (LCA) KT was performed 4 years after ASCT. No recurrence occurred in a 2-year follow up. Conclusion MM is the most frequent malignancy in dialytic population; the need for KT in MM remains high. ASCT improves the quality of life and offers higher survival in patients with myeloma/MGRS/amyloidosis-related ESRD. Therefore the combination of chemotherapy/ASCT and KT is pivotal to pursue renal restoring. Since high risk of recurrence larger study are required to clarify the better follow up period after MM remission and KT.

Baseline Serum Albumin and Proteinuria Predict Renal Response after Autologous Stem Cell Transplantation in AL Amyloidosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1166-1166
Author(s):  
Nelson Leung ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
Mark R. Litzow ◽  
Shaji K. Kumar ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Light Chain ◽  
Al Amyloidosis ◽  
Baseline Serum ◽  
Monoclonal Protein ◽  
Renal Response ◽  
Hematologic Response ◽  
Organ Response

Abstract Introduction: High dose melphalan followed by autologous stem cell transplantation (ASCT) is an effective treatment for patients with light chain associated (AL) amyloidosis. Longer patient survival and higher rates of organ response have now been documented by multiple studies. However, predictors of organ response remain unknown. Previously, we have reported the benefits of renal response after ASCT in this population. This study was conducted to investigate the characteristics that would predict renal response after ASCT. Methods: The study was performed retrospectively on consecutive patients that underwent ASCT at our institution from March of 1996 to December of 2004. Exclusion criteria include baseline proteinuria &lt; 1 g/d, dialysis prior to ASCT and lack of laboratory data at follow up to determine renal response. Renal response was defined by &gt; 50% reduction in baseline proteinuria with &lt; 25% decline in renal function as measured by serum creatinine. Treatment related mortality and dialysis dependence prior to meeting criteria of response were viewed as treatment failures. Hematologic response was determined by 50% reduction of monoclonal protein (free light chain) or complete eradication if the monoclonal protein was too small to be quantified. Results: A total of 135 patients met criteria for study. Median age was 56.2 years at the time of transplant, 53.7% were male. Median baseline proteinuria and GFR were 6.4 g/d and 70 ml/min/1.73m2 respectively. Renal response was achieved in 35.6% of the patients while hematologic response was 71.1% in the 128 patients evaluated. Patient’s age, sex, albumin, GFR, proteinuria, conditioning regimen, and hematologic response were evaluated and the following were found to be associated with renal response: albumin (p = 0.001), proteinuria (p = 0.008), and hematologic response (p = 0.0002). The cutoff for albumin was found to be 1.6 mg/dl and proteinuria was 3.5 g/d. Multivariate analysis using a logistic regression model showed hematologic response and proteinuria to be independent predictors of renal response. The impact of proteinuria and hypoalbuminemia was then investigated together (Table 1). When combined, they were a better predictor then either one alone (Hazard ratio = 6.34 for combined, 3.43 for proteinuria, 3.32 for hypoalbuminemia). The combination was also a better independent predictor of renal response in the multivariate analysis. In this group of patients, renal response was associated with longer survival but hematologic response was not (p = 0.02). Discussion: Our study showed that besides hematologic response, baseline serum albumin and proteinuria are independent predictors of renal response in AL patients after ASCT. Hypoalbuminemia and nephrotic range proteinuria, both markers of the severity of renal disease, have strong negative impact on response. This implies that there may be a limit to the reversibility of organ damage even when hematologic response is achieved. This study also points out the importance of organ (renal) response in this disease as hematologic response alone did not predict long term outcome. Our results suggest ASCT should be done early for AL to insure optimal organ response and patient outcome. Table 1 The Effects of Hypoalbuminemia and Proteinuria on Renal Response after ASCT Hypoalbuminemia & Proteinuria No Renal Response Renal Response None 39.3% 60.7% One 66.2% 33.8% Both 81.8% 18.2%

Bortezomib with Dexamethasone in Newly Diagnosed Patients with Primary Systemic Light Chain Amyloidosis or Multiple Myeloma-Associated AL Amyloidosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5036-5036 ◽  
Author(s):  
Beihui Huang ◽  
Juan Li ◽  
Junru Liu ◽  
Dong Zheng ◽  
Mei Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Side Effects ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Hematologic Response ◽  
Best Response ◽  
Organ Response

Abstract Abstract 5036 Objective: To assess the efficacy and tolerability of bortezomib with dexamethasone for patients with primary systemic light chain (AL) amyloidosis or multiple myeloma-associated AL amyloidosis. Methods: Twelve newly diagnosed patients with primary systemic AL amyloidosis and six patient with multiple myeloma-associated AL amyloidosis were treated with a combination of bortezomib (1. 3 mg/m2 d1, 4, 8, 11) and dexamethasone (20 mg d1–4). Results: Sixteen patients was evaluable. 12/16 had a hematologic response and 6/16 (37. 5%) a hematologic complete response. Median cycles to response was 1 cycle and median cycles to best response was 2 cycles. In patients with primary AL amyloidosis, 8/10 (80. 0%) had a hematologic response and 5/10 (50. 0%) a hematologic complete response. In patients with myeloma-associated AL amyloidosis, 7/10 (70. 0%) had a hematologic response and 1/6 (16. 7%) a hematologic complete response. Twelve patients (75. 0%) had a response in at least one affected organ, in which 7 in patients with primary AL amyloidosis and 5 in myeloma-associated AL amyloidosis. Person correlation between hematologic response and organ response was 0. 667 (p=0. 005). Fatigue, diarrhea and infection were the most frequent side effects. Three patients developed herpes zoster and had to stop chemotherapy. Conclusions: VD produces rapid and high hematological responses in the majority of patients with newly diagnosed AL regardless of primary or associated with myeloma. It is well tolerated with few side effects. This treatment may be a valid option as first-line treatment for newly diagnosed patients with primary systemic AL amyloidosis and multiple myeloma-associated AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

Outcomes of ASCT for cardiac AL-amyloidosis and cardiac light chain deposition disease.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 7035-7035
Author(s):  
Al-Ola A. Abdallah ◽  
Shebli Atrash ◽  
Aziz Bakhous ◽  
Daisy Alapat ◽  
Maurizio Zangari
Keyword(s):  
Light Chain ◽  
Al Amyloidosis ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

scholarly journals Hematologic Responses in Patients with Heavily Pretreated Light Chain Deposition Disease (LCDD) Receiving Daratumumab

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1985-1985
Author(s):  
Paolo Milani ◽  
Marco Basset ◽  
Andrea Foli ◽  
Giampaolo Merlini ◽  
Giovanni Palladini
Keyword(s):  
Partial Response ◽  
Light Chain ◽  
Cell Transplant ◽  
Light Chain Deposition Disease ◽  
Hematologic Response ◽  
Deposition Disease ◽  
Heavily Pretreated ◽  
Renal Progression ◽  
Line Of Therapy ◽  
Light Chain Deposition

Abstract Introduction: The monoclonal antibody daratumumab showed high response rates and a good safety profile in multiple myeloma and is being evaluated in clinical trials in AL amyloidosis. Light chain deposition disease (LCDD) is a rare monoclonal gammopathy of renal significance. Treatment directed against the underlying plasma cell clone can prevent renal progression. Bortezomib is commonly used upfront in these patients and daratumumab may represent a powerful novel option. Methods: We report the outcome of six patients with refractory light chain deposition disease (LCDD) treated with daratumumab at the Amyloidosis Research and Treatment Center of Pavia. All patients gave written informed consent. Hematologic response was assessed according to the International Society of Amyloidosis criteria. Results: Six patients (5 males and 1 female) received daratumumab intravenously at 16 mg/kg weekly for 8 weeks, followed by every other week infusions for 8 doses and then monthly infusions. Patients' clinical characteristics are reported in Table 1. All patients received daratumumab single agent except one who was treated with daratumumb and bortezomib combination (this patient received only 1 prior line of therapy). All patients were refractory to the last line of therapy. All patients received at least two months of therapy. All patients were previously treated with bortezomib, pomalidomide was used in 4 cases, lenalidomide, thalidomide and bendamustine in 2 cases each, and autologous stem cell transplant was performed in 4 subjects. The median time from LCDD diagnosis to daratumumab initiation was 8.3 years (range 8 - 147 months). Five of the 6 patients obtained hematologic response with at least a reduction of 50% of the dFLC value (partial response). Three patients obtained a very good partial response (dFLC <40 mg/L). The estimated glomerular filtration rate improved in one subject (from 30 to 45 mL/min per 1.73 m2) and in all the others remained stable. In 2 subjects treatment was temporarily discontinued due to pneumonia. Conclusions: This is the first report of the use of daratumumab in LCDD. This antibody yielded rapid and significant hematologic responses in five of six heavily pretreated patients with this disease, preventing renal progression. Daratumumab represents a promising option for these patients and larger, international studies are warranted. Disclosures Merlini: Akcea: Consultancy; Ionis: Consultancy; Prothena: Consultancy; Millenium: Consultancy; Janssen: Consultancy; Pfizer: Consultancy. Palladini:Celgene: Other: Travel support; Janssen: Membership on an entity's Board of Directors or advisory committees; Prothena: Honoraria.

Treatment with Oral Melphalan and Dexamethasone of An Extended Patient Population with AL Amyloidosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3889-3889 ◽  
Author(s):  
Giovanni Palladini ◽  
Paola Russo ◽  
Andrea Foli ◽  
Letizia Zenone Bragotti ◽  
Francesca Lavatelli ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Nyha Class ◽  
Fluid Retention ◽  
Phase Iii ◽  
High Dose ◽  
Al Amyloidosis ◽  
Hematologic Response ◽  
Heart Involvement ◽  
Phase Iii Trials ◽  
Organ Response

Abstract Abstract 3889 Poster Board III-825 Oral melphalan and dexamethasone (MDex) has been adopted in many referral centers as standard therapy for AL amyloidosis, particularly in patients who are not eligible for high dose melphalan (M) and autologous stem cell transplant (ASCT). A randomized trial failed to demonstrate the superiority of ASCT over MDex, and phase III trials are being designed to compare MDex with regimens including new drugs. However, only few small series of patients treated with MDex have been published so far. We report the outcome of 126 consecutive patients with AL amyloidosis who received first line MDex between January 2004 and December 2007. All the patients who were not eligible for ASCT with high dose M, due to any of the following conditions: age >60 years, N terminal natriuretic peptide type B (NT-proBNP) >332 ng/L, troponin I (cTnI) >0.1 ng/mL, glomerular filtration rate (eGFR) ≤50 mL/min, were included. Patients were given M (0.22 mg/Kg, or 0.16 mg/Kg if eGFR was <30 mL/min) and Dex (40 mg, or 20 mg in case of fluid retention >3% of body weight or complex ventricular arrhythmias at 24 h Holter ECG) on days 1-4 q28 days for up to 9 cycles. Treatment was discontinued if complete remission (CR) or partial hematologic response (PR) plus organ response (OR) was reached after 6 cycles, or in case of lack of response after 3 cycles. The International Society for Amyloidosis (ISA) consensus criteria for hematologic and organ response and progression were used. Progression free survival (PFS) was defined as the time to death or hematologic or organ progression according to the ISA criteria. Response and progression of NT-proBNP were defined as 3300 ng/L and 330% modifications. The median number of organs involved was 2 (range 1-5), 92 patients (73%) had heart involvement, with New York Heart Association (NYHA) class ≥2 heart failure in 66 cases (60%) and 93 patients (74%) had renal involvement, with eGFR <30 mL/min in 9 (7%). Cardiac TnI was >0.1 ng/mL in 27 patients (22%) and NT-proBNP was >332 ng/L in 99 (79%). Twenty-four patients (19%) experienced severe, though non fatal, adverse events. The most common was fluid retention (12%), that was significantly associated with NYHA class (p=0.02) and cTnI concentration (p<0.001). Four patients (3%) died on treatment due to progressive cardiac amyloidosis. Hematologic response was reached in 78 subjects (62%), with 33 CRs (26%). Median time to response was 3.5 months (range 0.7-13.2 months). Forty-two patients (33%) achieved OR. The mLVW thickness decreased by at least 2 mm in 6 (6%) of the 92 patients with heart involvement, whereas NT-proBNP response was achieved in 32 patients (35%) and was associated with improvement of NYHA class. Forty-two patients (33%) died. The median follow-up of living patients was 3 years (range 1.1-5.4 years). Median overall survival (OS) was not reached. Median PFS was 2.5 years. The multivariate analysis including variables measured at presentation showed that only NT-proBNP was independently associated with OS and PFS (p <0.001). Hematologic response improved OS (median 22 months vs. not reached, p<0.001) and PFS (median 6 vs. 40 months, p<0.001), and CR gave an advantage in OS (70% vs. 100% surviving at 3 years, p<0.001) and PFS (median 30 months vs. not reached, p<0.001) over PR. Patients who obtained NT-proBNP response had longer OS (62% vs. 88% surviving at 3 years, p=0.005) and PFS (median 18 vs. 40 months, p=0.01). Progression of NT-proBNP identified patients with poor outcome among non responders (median OS 6 months vs. not reached, p=0.02; PFS 3 vs. 15 months, p=0.006) and among patients in PR (median OS 19 months vs. not reached, p=0.03; PFS 14 vs. 32 months, p=0.05). The multivariate analysis including variables measured 6 months after treatment initiation showed that only the absolute concentrations of involved free light chains (FLC) and NT-proBNP remaining after therapy independently affected survival (p <0.001). The FLC (62 mg/L) and NT-proBNP (3100 ng/L) cutoff best predicting survival after MDex were identified. Estimated OS at 3 years was 94% in patients with both NT-proBNP and FLC below the cutoff, 60% in subjects with 1 marker above the cutoff and 30% in those with both markers above the cutoff (p=0.001). Future efforts should be directed to improve the response rate and rapidity of response, while preserving treatment tolerability and feasibility. Phase III trials comparing MDex with MDex associated with new agents are being developed. Disclosures: No relevant conflicts of interest to declare.

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