scholarly journals Epidemiology of Light-Chain Amyloidosis: A Population-Based Cohort Study in Taiwan

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1637-1637
Author(s):  
Hsin-An Hou ◽  
Chao-Hsiun Tang ◽  
Choo Hua Goh ◽  
Sarah Siggins ◽  
Shih-Pei Shen ◽  
...  
Keyword(s):  
Cohort Study ◽  
Mortality Rate ◽  
Light Chain ◽  
Research Funding ◽  
Population Based ◽  
Advisory Board ◽  
Al Amyloidosis ◽  
Prevalence Rates ◽  
Newly Diagnosed ◽  
All Cause Mortality

Abstract Introduction: AL (light-chain) amyloidosis is a rare disease with an incidence rate of approximately 12-13 per million population in Western countries. To date, the epidemiology of AL amyloidosis in Asian countries has not been described. Population-based clinical information about AL amyloidosis is needed to understand disease characteristics and the impacts of future treatments on the disease Methods: We conducted a retrospective cohort study using the Taiwan National Healthcare Insurance Research database (NHIRD) and Death Registry to estimate the incidence, prevalence, all-cause mortality rate and characteristics of patients with AL amyloidosis in Taiwan. All patients with confirmed newly diagnosed AL amyloidosis (ICD-10 E85.4: Organ-limited amyloidosis, E85.8: Other amyloidosis and E85.9: Amyloidosis, unspecified) from 01 January 2016 until 31 December 2019 were enrolled. Eligible patients had a biopsy record within 12 months prior to, or up to 6 months after the date of diagnosis of AL amyloidosis; and at least two consecutive outpatient claims and/or one inpatient claim amyloidosis in the NHIRD. Patients were followed up until dis-enrolment, death or study end (31 December 2019), whichever occurred first. Results: A total of 841 patients with newly diagnosed AL amyloidosis were identified in Taiwan during the period 01 January 2016 until 31 December 2019. The median age at diagnosis was 61.4 years and 58.7% were men. At diagnosis, cardiac disease was present in 28.54%, renal-related disease in 23.19% and had 7.85% had multiple myeloma (Table). The crude annual incidence of AL amyloidosis was 8.46 per million population in 2016 and 8.31 per million population in 2019 (Figure). The age-adjusted incidence rates were 5.73 and 5.26 per million population, respectively. The crude and age-adjusted prevalence rates of AL amyloidosis remained similar over the study period: the crude prevalence rates were 121 to 142 per million population, and age-adjusted prevalence rate were 81.52 to 99.84 per million population. The all-cause mortality rate ranged from 1.7 to 2.9 per 1000 patients over the study period but was highest (~10 per 1000) in patients aged ≥80 years. There were 501 patients (59.6%) with a biopsy report prior to the AL diagnosis index date. Presenting clinical symptoms were not available in the claims database so we assessed the time period from biopsy to diagnosis. The median time from biopsy until diagnosis was 3.8 months and was longer than 12 months in some patients, with little change observed from year to year. Conclusion: To our knowledge, this is the first known population-based cohort study of non-hereditary amyloidosis in Asia. The incidence of AL amyloidosis in Taiwan appears to be similar to Western countries with higher prevalence in Asia. There was no apparent change in the incidence or prevalence rates over the 4 years of the study. Diagnostic delay is recognized as an important limitation in the treatment of AL amyloidosis. Figure 1 Figure 1. Disclosures Goh: Janssen: Current Employment. Siggins: Janssen Pharmaceuticals: Current Employment. Qiu: Janssen Research & Development LLC: Current Employment, Current holder of individual stocks in a privately-held company. Chou: Abbvie: Honoraria, Other: Advisory Board, Research Funding; Celgene: Honoraria, Other: Advisory Board, Research Funding; IQVIA: Honoraria, Other: Advisory Board; Pfizer: Honoraria, Other: Advisory Board; Novartis: Honoraria, Other: Advisory Board; Bristol Myers Squibb: Honoraria, Research Funding; Kirin: Honoraria, Research Funding. Liu: Janssen Research & Development LLC: Current Employment, Current holder of individual stocks in a privately-held company.

scholarly journals Decreased Cardiac Ejection Fraction Is Associated with Worse Survival in Patients with Light Chain Amyloidosis Treated with Autologous Stem Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-42
Author(s):  
Abdullah S. Al Saleh ◽  
Iuliana Vaxman ◽  
Harsh Parmar ◽  
Alissa Visram ◽  
M Hasib Sidiqi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Ejection Fraction ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Light Chain ◽  
Research Funding ◽  
Cardiac Involvement ◽  
Advisory Board ◽  
Al Amyloidosis

Introduction: Cardiac involvement is one of the main predictors for survival in patients with light chain (AL) amyloidosis. Biomarkers such as Troponin T and N-terminal pro b-type natriuretic peptide (NT-proBNP) are used routinely for detecting cardiac involvement. In addition echocardiogram (ECHO) is used to determine septal and left ventricular wall thickness and strain. Most patients with AL present with preserved ejection fraction (EF) however, the outcomes of AL patients undergoing autologous stem cell transplantation (ASCT) with decreased EF are not very well described. Methods: We retrospectively reviewed patients who had a diagnosis of AL amyloidosis and received ASCT between March 1996 and September 2017. All patients had an ECHO done before ASCT and the EF was documented. In our practice, the threshold for performing ASCT is an EF >40%. We evaluated the outcomes of patients who had an EF <55% compared to patients with an EF ≥55%. The baseline characteristics were compared between patients with high and low EF. Progression-free survival (PFS) was defined as time from ASCT to disease progression, relapse, or death of any cause. Overall survival (OS) was calculated from time of ASCT to death of any cause. Univariate and multivariate analysis for PFS and OS were done using the following variables: age>65 vs. ≤65 years, Mayo 2012 stage 3/4 vs. 1/2, bone marrow plasma cell percentage (BMPC) ≥ 10% vs. <10%, organs involved >2 vs. ≤2, melphalan conditioning 200mg/m2 vs. 140 mg/m2 ,ASCT year >2010 vs. ≤2010, and EF <55% vs. ≥55%. Results: We identified 716 patients and 69 (10%) had an EF<55%, with most (n=63, 91%)having cardiac involvement . Compared to patients with EF ≥55%, patients with EF <55% were more likely to have Mayo 2012 stage 3/4 (58% vs. 22%, P<0.0001) and more likely to have thicker interventricular septum (median 14 vs. 12 mm, P<0.0001). The day 100 transplant related mortality (TRM) was higher in patients with EF <55% compared to EF ≥55% (19% vs. 6%, P=0.0006). In patients with Mayo 2012 stage 3/4, the day 100 TRM was higher in patients with an EF<55% compared to EF ≥55% (27% vs. 7%, P=0.004). Overall, PFS and OS were significantly shorter in patients with EF <55% compared to patients with EF ≥55% (Figure 1 A,B). Evaluating PFS and OS according to EF specifically in Mayo 2012 stage 3/4 patients is displayed in Figure 1 (C,D). Predictors for PFS included Mayo 2012 stage 3/4 vs. 1/2 (hazard ratio (HR): 1.4, P=0.006), BMPC ≥ 10% vs. <10% (HR: 1.5,P=0.0005), melphalan conditioning 200mg/m2 vs. 140 mg/m2 (HR:0.7, P=0.01), ASCT year >2010 vs. ≤2010 (HR: 0.7, P=0.01), and EF <55% vs. ≥55% (HR: 1.5, P=0.02). For OS, age >65 vs. ≤65 years (HR:1.4, P=0.04), Mayo 2012 stage 3/4 vs. 1/2 (HR: 1.96, P<0.0001), melphalan conditioning 200mg/m2 vs. 140 mg/m2 (HR:0.5, P<0.0001), BMPC ≥ 10% vs. <10% (HR: 1.8, P=0.03), ASCT year >2010 vs. ≤2010 (HR: 0.5, P<0.0001), and EF <55% vs. ≥55%(HR:1.9, P=0.003) were predictive. Conclusion: Having an EF <55% is associated with a higher day 100 TRM and is an independent predictor for PFS and OS in patients with AL amyloidosis undergoing ASCT. Disclosures Sidiqi: Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria, Other: Travel grant. Dingli:Alexion: Consultancy; Apellis: Consultancy; Sanofi-Genzyme: Consultancy; Millenium: Consultancy; Bristol Myers Squibb: Research Funding; Karyopharm Therapeutics: Research Funding; Janssen: Consultancy; Rigel: Consultancy. Kapoor:Janssen: Research Funding; GlaxoSmithKline: Research Funding; Cellectar: Consultancy; Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Takeda: Honoraria, Research Funding; Amgen: Research Funding. Dispenzieri:Janssen: Research Funding; Pfizer: Research Funding; Alnylam: Research Funding; Intellia: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Kumar:AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Merck: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Dr. Reddy's Laboratories: Honoraria; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Kite Pharma: Consultancy, Research Funding; Novartis: Research Funding; Sanofi: Research Funding; MedImmune: Research Funding; Karyopharm: Consultancy; BMS: Consultancy, Research Funding; Tenebio: Other, Research Funding; Genecentrix: Consultancy; Cellectar: Other; Carsgen: Other, Research Funding. Gertz:Spectrum: Other: personal fee, Research Funding; Janssen: Other: personal fee; Sanofi: Other; Research to Practice: Other; Celgene: Other; Medscape: Other: personal fee, Speakers Bureau; Proclara: Other; DAVA oncology: Speakers Bureau; Alnylam: Other: personal fee; Johnson and Johnson: Speakers Bureau; Physicians Education Resource: Other: personal fee; Teva: Speakers Bureau; Ionis/Akcea: Other: personal fee; Amgen: Other: personal fee; Springer Publishing: Patents & Royalties; Aurora Bio: Other; Appellis: Other: personal fee; Abbvie: Other; Annexon: Other: personal fee; Prothena: Other: personal fee.

scholarly journals Retroperitoneal Involvement of Light Chain Amyloidosis-Case Series and Literature Review

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-38
Author(s):  
Iuliana Vaxman ◽  
Alissa Visram ◽  
Oren Pasvolsky ◽  
Shaji K. Kumar ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Weight Loss ◽  
Clinical Trials ◽  
Light Chain ◽  
Research Funding ◽  
Case Series ◽  
Advisory Board ◽  
Ct Scans ◽  
Al Amyloidosis ◽  
Nephrostomy Tube

Introduction Amyloidosis is a disease caused by aggregates of misfolded insoluble proteins that accumulate extracellularly and impair organ function. The most common type of systemic amyloidosis is immunoglobulin light chain (AL), which typically involves the heart, kidneys, nerves, liver, gastrointestinal tract and soft tissue. Retroperitoneal involvement in the setting of systemic AL amyloidosis is rare and only published as case reports. Aim To report characteristics and outcomes of AL amyloidosis patients that had retroperitoneal deposition of amyloid in the novel agent era. Methods Retrospective study of all consecutive systemic AL amyloidosis patients with retroperitoneal involvement at all three Mayo Clinic sites and at Davidoff cancer center, a tertiary hospital in Israel. All patients were diagnosed with retroperitoneal involvement based on computerized tomography (CT) scans. All patients had biopsy proof of amyloidosis with Congo red staining. Patients that were diagnosed with localized amyloidosis of the bladder or ureter and patients that did not receive systemic treatment were excluded. Results We identified 11 patients with systemic AL amyloidosis and retroperitoneal involvement between January 2001 and December 2018. Median age at diagnosis was 65 years (range 50-72). Ten were male (91%) and one was female. Five patients had amyloid secondary to B cell lymphoma (4 Waldenstrom macroglobulinemia and 1 had follicular lymphoma). The involved light chain was lambda in 7 patients and kappa in 4 patients. All patients were diagnosed with retroperitoneal involvement of amyloidosis at presentation (not at progression). In 10 out of the 11 patients, amyloidosis in the retroperitoneum was confirmed by a core biopsy of the retroperitoneal tissue. Significant unintentional weight loss (more than 5 kg) at presentation was documented in six patients (55%). Seven patients (64%) had enlarged lymph nodes on the CT scan. Three patients had CT finding of calcifications, and the distribution pattern was diffuse in 7 patients (64%), while 4 patients presented with a mesenteric mass. Six patients (55%) had evidence of amyloid deposits in the bone marrow and 3 patients (27%) had a positive fat pad. Periorbital purpura was observed in one patient and none had macroglossia. Therapy regimens used are described in table 1. Five patients underwent an autologous stem cell transplantation (ASCT). Eight patients (72%) presented with unilateral (N=2) or bilateral (N=6) hydronephrosis and 7 had nephrostomy tubes or stents inserted. The median follow-up from stent/nephrostomy tube insertion was 33 months (IQR 8-91). Regression of the deposition was documented in one patient and one patient was able to have his nephrostomy tube removed. One patient (9%) developed end stage renal disease requiring dialysis. Data regarding hematologic response rates were available for 9 patients and all responded and achieved hematologic PR or better. The median follow-up for all surviving patients was 91 months (IQR 27-179). Seven of the patients are currently alive. The median OS from diagnosis was 150 months. Figure 1 shows typical diffuse retroperitoneal involvement of AL amyloidosis on a CT scan. Review of the literature revealed 5 cases of retroperitoneal involvement of systemic AL amyloidosis. Most were reports published before routine typing of amyloid. Four of the five cases (80%) were male. The ages ranged from 46 to 80 years. Four of the five cases (80%) presented with weight loss. Two patients had calcifications on the CT scans, and one had a large pleural effusion. Conclusions We report a multicenter case series of 11 patients diagnosed with systemic AL amyloidosis with retroperitoneal involvement, all received systemic chemotherapy. We found male predominance in our cohort. Eight patients presented with hydronephrosis, and only one patient had the nephrostomy tube removed successfully after systemic therapy. ORR was 100% and median OS from diagnosis was 150 months, suggesting that retroperitoneal deposition might confer improved prognosis compared to the general amyloid population. Disclosures Kumar: Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; Dr. Reddy's Laboratories: Honoraria; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Karyopharm: Consultancy; BMS: Consultancy, Research Funding; Carsgen: Other, Research Funding; Genecentrix: Consultancy; Cellectar: Other; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Adaptive Biotechnologies: Consultancy; MedImmune: Research Funding; Novartis: Research Funding; Kite Pharma: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Tenebio: Other, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments. Dispenzieri:Intellia: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding. Dingli:Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Alexion: Consultancy; Apellis: Consultancy; Millenium: Consultancy; Sanofi-Genzyme: Consultancy; Janssen: Consultancy; Karyopharm Therapeutics: Research Funding. Kapoor:Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; GlaxoSmithKline: Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Takeda: Honoraria, Research Funding. Gertz:DAVA oncology: Speakers Bureau; Appellis: Other: personal fee; Proclara: Other; Medscape: Other: personal fee, Speakers Bureau; Springer Publishing: Patents & Royalties; Annexon: Other: personal fee; Research to Practice: Other; Celgene: Other; Prothena: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Physicians Education Resource: Other: personal fee; Abbvie: Other; Johnson and Johnson: Speakers Bureau; Teva: Speakers Bureau; Janssen: Other: personal fee; Amgen: Other: personal fee; Alnylam: Other: personal fee; Ionis/Akcea: Other: personal fee; Aurora Bio: Other; Sanofi: Other.

scholarly journals Early Serum Free Light Chain Response after High-Dose Melphalan and Stem Cell Transplantation Predicts Hematologic Response in AL Amyloidosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 26-26
Author(s):  
Vanessa Fiorini Furtado ◽  
Dina Brauneis ◽  
Shayna Sarosiek ◽  
Karen Quillen ◽  
Vaishali Sanchorawala
Keyword(s):  
Light Chain ◽  
Research Funding ◽  
Amyloid Fibrils ◽  
Advisory Board ◽  
Free Light Chain ◽  
Light Chains ◽  
High Dose ◽  
Al Amyloidosis ◽  
Serum Free Light Chain ◽  
High Dose Melphalan

Introduction Immunoglobulin light chain (AL) amyloidosis is a rare disease caused by a clonal plasma cell dyscrasia producing monoclonal light chains that misfold and form amyloid fibrils which can deposit in a variety of tissues and organs. This deposition of amyloid fibrils can lead to progressive organ impairment, multi-organ failure, and death if left untreated. High-dose melphalan and autologous stem cell transplantation (HDM/SCT) is known to improve patient outcomes with hematologic complete responses (CR) rates of 25-67%. Hematologic CR is currently defined as the absence of monoclonal protein in serum and urine by immunofixation electrophoreses and normal serum free light chain ratio (FLCR). Studies have shown that even among patients achieving a normal FLCR after initial therapy with HDM, persistent elevation of the involved FLC (hiFLC) predicts poor prognosis. Serum half-life of FLCs is approximately 2-6 hours, even with diminished glomerular filtration rates, and could be a tool for early treatment response evaluation. We sought to determine the extent to which early FLC responses after HDM/SCT predict hematologic complete response (CR) at 6 months. Methods We analyzed patients with AL amyloidosis who underwent HDM/SCT from 2012-2019 at Boston Medical Center. Exclusion criteria included death within 100 days, lack of FLC data at any time point, pre-SCT normal FLC concentrations and ratio, and chronic renal insufficiency (serum creatinine >1.3 mg/dL) with a normal FLC ratio. All subjects received a total of 140-200 mg/m2 melphalan IV in equally divided doses on days -3 and -2. Stem cells were infused on day 0. FLC measurements were obtained early in the peri-SCT period (< 1 month), at 6 months, and at 12 months after HDM/SCT. The patients were evaluated for response according to the consensus response criteria at 6 months. Statistical analysis to compare CR at 6 months and early post-SCT free light chain levels was performed by Chi-square with significance considered at p<0.05. Results Of the 113 patients with AL amyloidosis treated with HDM/SCT during the specified time period, 32 were excluded (4 died within 100 days of SCT, 15 had normal FLCs pre-SCT, 5 lacked data, and 8 had chronic renal insufficiency (Cr >1.3 mg/dL) with normal FLCR. A total of 81 subjects (females=30) were analyzed. Median follow-up from SCT was 27.6 months (range, 6-145). Median time of early post-SCT FLC measurement was 8 days (range, 7-30). Median age at diagnosis was 58 years (range 30-79) and the iFLC was lambda in 81.5% (n = 66) of patients. Median number of bone marrow plasma cells was 10% (range, 1-50). The mean absolute involved FLC was 196 mg/L ±221 prior to SCT, 60 mg/L ± 77 in the early post-SCT period, 92 mg/L ± 152 at 6 months post-SCT. In early post-SCT period, 39.5% (n=32) had iFLC <20 mg/L, 28% (n=16/57) had dFLC<10 mg/L, and 84% (n=48/57) had normal FLCR. Early post-SCT dFLC <10 mg/dL and early post-SCT iFLC <20 mg/L were statistically associated with prediction of hematologic CR at 6 months (p=0.025 and p=0.001, respectively). However, early post-SCT normal FLCR was not associated with predicting hematologic CR at 6 months. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of early post-SCT iFLC <20 mg/L, dFLC <10 mg/L and normal FLCR to predict hematologic CR at 6 months are presented in table 1. Conclusion This study concludes that achievement of dFLC <10 mg/L and iFLC <20 mg/L in the early post-SCT period is associated with prediction of hematologic CR at 6 months. Early post-SCT dFLC <10 mg/L could be considered a tool for early evaluation of treatment response following HDM/SCT in AL amyloidosis. Key words: immunoglobulin light chains; AL amyloidosis, HDM/SCT Disclosures Sarosiek: Spectrum: Research Funding. Sanchorawala:Caelum: Research Funding; Prothena: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Proclara: Other: advisory board; Abbvie: Other: advisory board; UpToDate: Patents & Royalties; Oncopeptide: Research Funding; Regeneron: Other: advisory board; Caleum: Other: advisory board; Janssen: Research Funding.

scholarly journals Sars-Cov-2 Infection and Systemic Light Chain Amyloidosis: The International Society of Amyloidosis' Survey

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-11
Author(s):  
Paolo Milani ◽  
Vaishali Sanchorawala ◽  
Ramon Lecumberri ◽  
Sunil Saith ◽  
Mathew S. Maurer ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Data Collection ◽  
Board Of Directors ◽  
International Society ◽  
Light Chain ◽  
Research Funding ◽  
Advisory Board ◽  
Al Amyloidosis ◽  
Advisory Committees ◽  
Heart Involvement

Introduction: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has become a global health crisis since it was first reported in December 2019. In a subset of infected subjects, pneumonia, multi-organ failure, and eventually death can occur. Frail patients and those with comorbidities are believed to be at increased risk of severe manifestations of SARS-CoV-2 infection. Patients with light chain (AL) amyloidosis have a hematologic malignancy that causes multi-organ dysfunction and can be at higher risk of complications and death. The International Society of Amyloidosis (ISA) has issued a guidance (Kastritis et al. BJH 2020, https://cms.cws.net/content/isaamyloidosis.org/files/ISA%20recommendations%20Covid-19%20v_%203_3.pdf) for patients with amyloidosis during the pandemic and called for an international data collection in April 2020. Aim of this study is to report the preliminary data of the ongoing international survey regarding systemic AL amyloidosis and COVID-19. Methods: The survey was proposed by the ISA Board and approved by the coordinating institution's Ethics Committee. All members of the ISA were invited to participate by email and a link for participation is online on ISA website. RedCap software was used for the data collection. Results: Twelve Institutions requested the access to the data collection system from 7 countries. At the data lock of July 26, 2020, 29 patients with systemic amyloidoses were collected from 7 different Institutions. Systemic AL amyloidosis patients reported so far were 19: 12 from the Pavia Amyloidosis Research and Treatment Center (Italy), 3 from the Boston Medical Center (USA), and 1 patient each from the Columbia University Hospital (New York, USA), Hospital Clinic (Barcelona, Spain), Clinica Universitaria de Navarra (Navarra, Spain) and Amyloidosis Centrum (Heidelberg, Germany). Eleven (58%) had heart involvement, 8 (42%) had kidney and two or more organs were involved in 9 patients (47%). The most frequent comorbidities reported were history of hypertension in 7 (37%) and cardiovascular diseases in 3 (16%). Four (21%) patients were newly diagnosed and treatment-naïve at the time SARS-CoV-2 infection was documented. The remaining 15 patients had received a median number of 2 previous lines of therapy (range 1-3). Nine (47%) patients were on active chemotherapy at the time of COVID-19 infection. Five were receiving daratumumab combinations, and the 4 remaining patients were on cyclophosphamide, bortezomib and dexamethasone, oral melphalan and dexamethasone, lenalidomide and ixazomib. Relevant concomitant medications were anti-hypertensive drugs in 26% of cases and diuretics in 21%. One patient was on dialysis. COVID-19-related symptoms were fever 11 (58%), cough 8 (42%), anosmia and ageusia. Pneumonia was documented in 10 (53%) patients, 5 of whom had acute respiratory distress syndrome (ARDS) (26%). Four of them were treated with non-mechanical ventilation and one accessed intensive care support. Three of the 5 patients with severe COVID-19 had heart involvement, 2/5 had concomitant heart and kidney involved and 3 was infected while on active chemotherapy. Azytromicin was used in 6 (26%) cases, which was in combination with hydroxycloroquine in 4 of them. Three patients received steroids as treatment for SARS-CoV-2 infection, while anticoagulant therapy was used only in two cases. Lopinavir, tocilizumab and sarilumab were used in one patient each. Four patients (21%) died in the whole cohort. Three had ARDS and one patient died few weeks after the recovery of COVID-19 infection. All deceased patients had heart involvement, 2 were on active therapy (daratumumab plus bortezomib and ixazomib plus dexamethasone). Two patients with kidney involvement at diagnosis, one with ARDS and one with a radiological documented pneumonia treated with non-mechanical ventilation recovered from COVID-19 but developed subsequent worsening of renal function, requiring dialysis in one case. Conclusions: The fatality rate and the proportion of patients with severe COVID-19 in this series is in the higher range of reports from the general population. Severe SARS-CoV-2 infection can result in renal failure in patients with renal AL amyloidosis. Disclosures Milani: Janssen: Other: Speaker honoraria; Pfizer: Other: Speaker honoraria; Celgene: Other: Travel support. Sanchorawala:Oncopeptide: Research Funding; Abbvie: Other: advisory board; Proclara: Other: advisory board; Caleum: Other: advisory board; Regeneron: Other: advisory board; Prothena: Research Funding; Takeda: Research Funding; Janssen: Research Funding; UpToDate: Patents & Royalties; Caelum: Research Funding; Celgene: Research Funding. Cibeira:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational lectures; Akcea Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Other: Educational lectures; Amgen: Honoraria, Other: Educational lectures. Schönland:Janssen, Prothena, Takeda: Honoraria, Other: travel support to meetings, Research Funding. Palladini:Celgene: Other: Travel support; Jannsen Cilag: Honoraria, Other.

Bortezomib-Containing Regimens for the Treatment of Newly Diagnosed AL Amyloidosis: Experience of Two Centers in Canada

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2131-2131 ◽  
Author(s):  
Hatem Alahwal ◽  
Kevin W. Song ◽  
Peter Duggan ◽  
Heather J. Sutherland ◽  
Paola Neri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Light Chain ◽  
Cardiac Disease ◽  
Research Funding ◽  
Cardiac Response ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Dismal Prognosis ◽  
Organ Response ◽  
The Impact

Abstract Introduction Bortezomib is a novel, dipeptide boronic acid molecule that has shown anti-tumor activity against Multiple Myeloma (MM) and more recently has been demonstrated to be efficacious in the treatment of Light-chain Amyloidosis (AL). Bortezomib-based regimens have changed the landscape of the treatment of AL Amyloidosis due to high levels of response as well as the adequate tolerance. Based on the above mentioned, we aimed to assess the role of Bortezomib-containing regimens (BCR) for the treatment of newly diagnosed AL amyloidosis. Methods 80 consecutive patients have been treated with bortezomib-containing regimens at BCCA and TBCC in Calgary, AB and Vancouver, BC, Canada from 01/2010 to 01/2016. Among these cases, 51 (63.8%) have received CyBorD, 19 (23.7%) bortezomib (1.3 mg/m2) and dexamethasone and the rest Bortezomib in different combinations (Table 1). The primary objective of the study was to assess hematological and organ response. Results Clinical characteristics are shown in Table 1. Median age at diagnosis was 66 years and 51.1% of patients were male. At the time of analysis, 56 patients are still alive and 14 patients have already progressed. A HR was seen in 65/72 evaluable patients (ORR, 90%) after a median of 6 cycles (range, 1-24). Fourteen patients (17.5%) did not have measurable disease based on light chain levels. CR (34.7%) and VGPR (26.4%) were seen in 61% of cases. Organ response was achieved in 49% of cases. Cardiac response was observed in 40% of cases. Median OS and PFS have not been reached (Estimate, 67 and 41 months, respectively). (Fig 1a) However, OS was shorter in the group with severe heart involvement (NT-pro-BNP>5000 or BNP>1100) (p=0.03) (Fig 1b). In conclusion, BCR are efficacious for the treatment of newly diagnosed AL Amyloidosis, providing with a high degree of organ and hematological responses. The impact of BCR on advanced heart dysfunction cases remains unclear but it seems that these patients still require a different approach maintaining a dismal prognosis. Overall survival and advanced cardiac disease Overall survival and advanced cardiac disease Figure 1 PFS for the whole AL group treated with BCR Figure 1. PFS for the whole AL group treated with BCR Disclosures Song: Janssen: Honoraria; Otsuka: Honoraria; Celgene: Honoraria, Research Funding. Neri:Celgene and Jannsen: Consultancy, Honoraria. Bahlis:Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Onyx: Consultancy, Honoraria; BMS: Honoraria. Jimenez-Zepeda:Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria.

scholarly journals Phase 2 Trial of Ixazomib, Cyclophosphamide and Dexamethasone for Treatment of Previously Untreated Light Chain Amyloidosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 52-53
Author(s):  
Eli Muchtar ◽  
Morie A Gertz ◽  
Betsy Laplant ◽  
Francis K. Buadi ◽  
Nelson Leung ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Board Of Directors ◽  
Light Chain ◽  
Research Funding ◽  
Advisory Board ◽  
Organ Involvement ◽  
Al Amyloidosis ◽  
Advisory Committees ◽  
Hematologic Response ◽  
Phase 2 Trial

Background: Bortezomib, a proteasome inhibitor, has shown efficacy in the treatment of newly diagnosed and relapsed light chain (AL) amyloidosis, and the combination of bortezomib, cyclophosphamide and dexamethasone is a commonly used regimen in AL. Ixazomib is the first oral proteasome inhibitor to be approved, and the combination of ixazomib with cyclophosphamide and dexamethasone is an all oral effective regimen for the treatment of multiple myeloma. This phase 2 trial was designed to evaluate the efficacy of this regimen in patients with AL, who have not received any therapy. Patients and methods: Newly diagnosed patients with biopsy proven AL amyloidosis, with organ involvement requiring therapy, were enrolled if they had measurable disease (Serum immunoglobulin free light chain ≥5 mg/dL AND abnormal serum free light chain ratio) and adequate organ function. Patients with severe organ involvement were excluded (Alkaline phosphatase >750 U/L, creatinine clearance <30 mL/min or NT-ProBNP ≥ 7500 ng/dL). Treatment consisted of ixazomib 4 mg days 1, 8, 15; cyclophosphamide 500 mg PO weekly and dexamethasone 40 mg, weekly for twelve 28-day cycles, followed by ixazomib maintenance (days 1, 8, 15) at the last tolerated dose till progression. The primary objective was to determine the hematologic response rate of ixazomib, used in combination with cyclophosphamide and dexamethasone in patients with previously untreated AL. A one-stage binomial design was utilized to test the null hypothesis that the hematologic response rate is at most 30% against the alternative hypothesis that it is at least 50%, with 85% power and 9% type I error. Results: Thirty-five patients were enrolled, median age was 67 (range 38-78) years; 69% were male. Organ involvement included cardiac in 23 (65.7%), renal in 19 (54.3%), and nervous system involvement in 5 (14.3%). At data cutoff 8 patients still remain on study with a median follow up of 4.4 months for those who are alive. Across the trial a median of 4 cycles (range 0-23) of treatment have been completed; the most common reason for going off study was institution of alternate therapy in 17 patients (63%). The overall hematologic response was 57% (20/35) and included amyloid CR in 5 (14%), VGPR in 9 (26%) and a PR in 6 (17%) patients. Confirmed organ responses have been observed in 5 patients so far, 2 each for cardiac and renal and 1 hepatic. The median PFS and OS have not been reached; 4 patients had hematological progression; 6 patients (17%) have died. Across 193 cycles of treatment administered, dose modification was required in 5, 3, and 10 patients, respectively, for ixazomib, cyclophosphamide and dexamethasone. A grade 3 or higher adverse event (AE), at least possibly attributed to the study drugs, was observed in 41% of patients. The figure shows the maximum grade of adverse events for individual patients seen in more than one patient across the study. Conclusions: The all-oral regimen of ixazomib, cyclophosphamide, and dexamethasone is active in patients with previously untreated AL amyloidosis with hematologic responses observed in 57% of patients, including complete responses. Organ response has been observed but will likely need longer follow up for accurate assessment, given the delay in organ responses in this disease. Further evaluation of this combination is warranted. Disclosures Gertz: Alnylam: Consultancy; Ionis/Akcea: Consultancy; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Data Safety Monitoring board from Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Advisory Board for Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Advisory Board for Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Consultancy; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding; NCI SPORE MM: Research Funding; Prothena: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Appellis: Consultancy. Kapoor:Celgene: Honoraria; GlaxoSmithKline: Research Funding; Takeda: Honoraria, Research Funding; Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; Cellectar: Consultancy. Larsen:Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dingli:Apellis: Consultancy; Janssen: Consultancy; Sanofi-Genzyme: Consultancy; Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Karyopharm Therapeutics: Research Funding; Alexion: Consultancy; Millenium: Consultancy. Dispenzieri:Janssen: Research Funding; Intellia: Research Funding; Alnylam: Research Funding; Celgene: Research Funding; Pfizer: Research Funding; Takeda: Research Funding. Kumar:Adaptive Biotechnologies: Consultancy; Carsgen: Other, Research Funding; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genecentrix: Consultancy; Dr. Reddy's Laboratories: Honoraria; Tenebio: Other, Research Funding; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; BMS: Consultancy, Research Funding; Sanofi: Research Funding; Novartis: Research Funding; Kite Pharma: Consultancy, Research Funding; Karyopharm: Consultancy; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Merck: Consultancy, Research Funding; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Cellectar: Other; MedImmune: Research Funding.

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