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

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.

scholarly journals Uptake and detection rate of a stepwise cardiometabolic disease detection program in primary care—a cohort study

2019 ◽  
Vol 30 (3) ◽  
pp. 402-407
Author(s):  
Daphne M Stol ◽  
Monika Hollander ◽  
Ilse F Badenbroek ◽  
Mark M J Nielen ◽  
François G Schellevis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Primary Care ◽  
Cohort Study ◽  
High Risk ◽  
Newly Diagnosed ◽  
Additional Risk ◽  
High Risk Patients ◽  
Detection Program ◽  
Risk Patients

Abstract Background Early detection and treatment of cardiometabolic diseases (CMD) in high-risk patients is a promising preventive strategy to anticipate the increasing burden of CMD. The Dutch guideline ‘the prevention consultation’ provides a framework for stepwise CMD risk assessment and detection in primary care. The aim of this study was to assess the outcome of this program in terms of newly diagnosed CMD. Methods A cohort study among 30 934 patients, aged 45–70 years without known CMD or CMD risk factors, who were invited for the CMD detection program within 37 general practices. Patients filled out a CMD risk score (step 1), were referred for additional risk profiling in case of high risk (step 2) and received lifestyle advice and (pharmacological) treatment if indicated (step 3). During 1-year follow-up newly diagnosed CMD, prescriptions and abnormal diagnostic tests were assessed. Results Twelve thousand seven hundred and thirty-eight patients filled out the risk score of which 865, 6665 and 5208 had a low, intermediate and high CMD risk, respectively. One thousand seven hundred and fifty-five high-risk patients consulted the general practitioner, in 346 of whom a new CMD was diagnosed. In an additional 422 patients a new prescription and/or abnormal diagnostic test were found. Conclusions Implementation of the CMD detection program resulted in a new CMD diagnosis in one-fifth of high-risk patients who attended the practice for completion of their risk profile. However, the potential yield of the program could be higher given the considerable number of additional risk factors—such as elevated glucose, blood pressure and cholesterol levels—found, requiring active follow-up and presumably treatment in the future.

Survival in Patients with Newly Diagnosed Myeloma Undergoing Therapy with Lenalidomide and Dexamethasone: Impact of High-Risk Cytogenetic Risk Status on Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 95-95 ◽  
Author(s):  
Prashant Kapoor ◽  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E Witzig ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Plasma Cell ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Impact ◽  
Standard Risk

Abstract Background: Multiple myeloma (MM) is a heterogeneous disease with very divergent outcomes that are dictated in a large part by specific cytogenetic abnormalities, as well as other prognostic factors such as the proliferative rate of marrow plasma cells. Prognostic systems incorporating these factors have shown clinical utility in identifying high-risk patients, and are increasingly being utilized for treatment decision-making. However, the prognostic relevance of these factors may change with the application of novel therapies. The objective of this study was to determine the impact of risk-stratification (incorporating plasma cell metaphase cytogenetics, interphase fluorescent in-situ hybridization (FISH) and the slide-based plasma cell labeling index (PCLI)) in a cohort of patients with newly diagnosed MM treated initially with lenalidomide + dexamethasone (Rev-Dex). Methods: From March 2004 to November 2007, 100 consecutive patients treated with Rev (25mg/day) on days 1 through 21 of a 4-week cycle in combination with dexamethasone as initial therapy for newly diagnosed myeloma, were identified. High-risk MM was defined as presence of any one or more of the following: hypodiploidy, monoallelic loss of chromosome 13 or its long arm (by metaphase cytogenetics only), deletion of p53 (locus 17p13) or PCLI ≥ 3% or immunoglobulin heavy chain (IgH) translocations, t(4;14) (p16.3;q32) or t(14;16)(q32;q23) on FISH. PFS and OS survival estimates were created using the Kaplan Meier method, and compared by log-rank tests. Results: The median estimated follow-up of the entire cohort (N=100) was 36 months. The median PFS was 31 months; the median OS has not been reached. The 2- and 3-year OS estimates were 93% and 83%, respectively. 16% patients were deemed high-risk by at least one of the 3 tests (cytogenetics, FISH or PCLI). Response rates (PR or better) were 81% versus 89% in the high-risk and standard risk groups, respectively, P=NS; corresponding values for CR plus VGPR rates were 38% and 45% respectively. The median PFS was 18.5 months in high-risk patients compared to 37 months in the standard-risk patients (n=84), P<0.001(Figure). Corresponding values for TTP were 18.5 months and 36.5 months, respectively, P=<0.001. OS was not statistically significant between the two groups; 92% 2-year OS was noted in both the groups. Overall, 95 patients had at least one of the 3 tests to determine risk, while 55 patients could be adequately stratified based on the availability of all the 3 tests, or at least one test result that led to their inclusion in the high-risk category. The significant difference in PFS persisted even when the analysis was restricted to the 55 patients classified using this stringent criterion; 18.5 months vs. 36.5 months in the high-risk and standard- risk groups respectively; P<0.001. In a separate analysis, patients who underwent SCT before the disease progression were censored on the date of SCT to negate its effect, and PFS was still inferior in the high-risk group (p=0.002). Conclusion: The TTP and PFS of high-risk MM patients are inferior to that of the standard-risk patients treated with Rev-Dex, indicating that the current genetic and proliferation-based risk-stratification model remains prognostic with novel therapy. However, the TTP, PFS, and OS obtained in high-risk patients treated with Rev-Dex in this study is comparable to overall results in all myeloma patients reported in recent phase III trials. In addition, no significant impact of high-risk features on OS is apparent so far. Longer follow-up is needed to determine the impact of risk stratification on the OS of patients treated with Rev-Dex. Figure Figure

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.

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.

scholarly journals Phase II Trial of Cyclophosphamide, Lenalidomide and Dexamethasone (CYCLO-LEN-DEX) for Previously Untreated Patients with Light-Chain Amyloidosis (AL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2135-2135
Author(s):  
Joan Blade ◽  
Albert Oriol ◽  
Juan José Lahuerta ◽  
Maria-Victoria Mateos ◽  
Javier de la Rubia ◽  
...  
Keyword(s):  
Partial Response ◽  
Board Of Directors ◽  
Cardiac Involvement ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Hematologic Response ◽  
Organ Response ◽  
New Treatment ◽  
Good Partial Response

Abstract Background: Treatment with oral melphalan and dexamethasone has been adopted as the standard of care for newly diagnosed patients with immunoglobulin light chain (AL) amyloidosis not eligible for high-dose melphalan and stem cell transplantation (HDM/SCT). However, new treatment options are still needed for this patient population. Aim: Based on the activity of IMiDs® immunomodulatory drugs in relapsed/refractory AL amyloidosis, we designed a multicenter prospective, phase II trial with lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients not eligible for autologous transplant. Patients and methods: The main inclusion criteria were newly diagnosed AL amyloidosis confirmed by biopsy, significant organ involvement, cardiac ejection fraction over 50%, serum creatinine below 3 mg/dL, and not being eligible for autologous transplant. Treatment schedule consisted of 6 cycles of lenalidomide at 15 mg orally (po) on days 1 to 21, dexamethasone at 20 mg po on days 1 to 4 and 9 to 12, and cyclophosphamide at 300 mg/m2 intravenously (iv) on days 1 and 8 every 28 days, followed by 6 more cycles of lenalidomide at the same dose, dexamethasone at 20 mg po on days 1 to 4 and cyclophosphamide 300 mg/m2 iv on day 1. After these 12 cycles, maintenance with lenalidomide (10 mg po on days 1 to 21) and dexamethasone (20 mg po on days 1 to 4) was planned for three additional years or until discontinuation due to intolerance or disease progression. All patients received prophylaxis of thromboembolic events with oral aspirin (100 mg po daily) or subcutaneous low-molecular-weight heparin. The primary endpoint was hematologic response. Diagnosis of AL amyloidosis, definition of organ involvement and response criteria followed the Consensus Opinion from the Xth International Symposium on Amyloid and Amyloidosis (Gertz et al, Am J Hematol 2005), adding the very good partial response category included in the recently reported criteria (Palladini et al, J Clin Oncol 2012). Assessments of response were performed at the beginning of each cycle during the treatment period and every 3 months during the maintenance phase. Results: From September 2010 to December 2012, 28 patients were enrolled in the study. Twenty-three patients had cardiac involvement, with cardiac stage 3 in 14 of them. The overall hematologic response rate was 46%, including 7 patients (25%) with complete response, 5 patients (18%) with very good partial response and 1 patient (3%) with partial response. The organ response rate was 46% and was only observed among patients who achieved hematologic response. The organ response was reached in 10 (43%) of the 23 patients with renal involvement and 6 (26%) of the 23 patients with cardiac involvement. In 4 patients lenalidomide was reduced or discontinued due to toxicity. A therapy-related serious adverse event was reported in 6 patients. No significant cytopenias and no second primary malignancies (SPM) were observed. So far, 11 patients remain on the study. Seventeen (60%) have been discontinued mostly due to death secondary to cardiac or renal AL-related late events (8 patients), progression or lack of response (4), and toxicity (3). After a median follow up of 24 months, the median PFS and OS have not been reached, being significantly longer in responders. The estimated probability of PFS and OS for responders was 92% at 34 months. In contrast, the median PFS and OS for non-responders were only 1.9 and 2.4 months, respectively. Finally, according to Mayo Clinic risk stratification based on cardiac biomarkers, median OS for patients with stage I-II has not been reached (the 2-year estimate was 100%), and was 2.2 months for stage III (p <0.001; Figure 1). Conclusions: Our results support the efficacy and safety of the combination lenalidomide, dexamethasone and cyclophosphamide as a new treatment option for patients with AL amyloidosis not eligible for ASCT, without the risk of neuropathy associated with bortezomib-based therapies. However, this regimen should be preferably used when the organ function is still preserved since patients with advanced stage disease, particularly those with severe cardiac involvement, are unlikely to benefit. Figure 1. Figure 1. Disclosures Blade: Janssen, Celgene and Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Lenalidomide. First-line therapy in combination for AL amyloidosis.. Oriol:Janssen and Celgene: Honoraria. Lahuerta:Celgene: Honoraria; Janssen: Honoraria. Mateos:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. de la Rubia:Janssen and Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fernandez de Larrea:Janssen and Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. San Miguel:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cibeira:Janssen and Celgene: Honoraria.

scholarly journals SPECIFICS OF ANTIHYPERTENSION THERAPY IN HYPERTENSIVES OF VARIOUS CARDIOVASCULAR RISK (BY THE REGISTRY OF CHRONIC NON-COMMUNICABLE DISEASES IN TYUMENSKAYA OBLAST)

2018 ◽  
Vol 17 (3) ◽  
pp. 4-10
Author(s):  
A. Yu. Efanov ◽  
Yu. A. Vyalkina ◽  
Yu. A. Petrova ◽  
Z. M. Safiullina ◽  
O. V. Abaturova ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Risk Level ◽  
Moderate Risk ◽  
High Risk Patients ◽  
Risk Patients ◽  
Very High

Aim. To assess the specifics of antihypertension therapy (AHT) in hypertensives of various cardiovascular risk, in the registry of chronic non-communicable diseases in Tyumenskaya oblast.Material and methods. A random sample studied, of 1704 patients with hypertension, inhabitants of Tyumenskaya oblast (region), ascribed to dispensary follow-up. Mean age 62±7,5 y.o. Of those 31,5% (n=537) males. The prevalence and efficacy of AHT assessed according to cardiovascular risk level. The significance was evaluated with the criteria χ2.Results. AHT was characterized by the growth of the frequency of treatment approaches with cardiovascular risk consideration. Regular treatment took 33,9% patients of low and moderate risk vs 41,3% of high and very high (p<0,01). In the male group such tendency also took place. Gender specifics of AHT was characterized by that in the groups of high and very high risk females took medications significantly more commonly than males — 46,6% vs 29,1% in high risk group (p<0,01) and 47,5% vs 30% in very high risk group (p<0,01). With the increase of the risk level, there was decline of treatment efficacy — from 95% in low risk group to 32,5% in very high risk group; 53,1% of the participants were taking monotherapy, 32,9% — two drugs, 14,0% — ≥3 drugs. With the increase of risk grade there is tendency to increase of combinational AHT, however with no significant increase of efficacy. Treatment efficacy in high and very high risk patients comparing to patients with low and moderate risk was significantly lower — 33,1% vs 69,7% (p<0,01), respectively. Statins intake among the high and very high risk patients was 10,6-11,0% males and 7,8% females (p<0,05).Conclusion. AHT in hypertensives in Tymenskaya oblast, under dispensary follow-up, is characterized by insufficient usage of combinational drugs. With the raise of cardiovascular risk there is tendency to higher rate of combinational AHT. However there is no significant increase in efficacy of treatment with the increase of medications number. A very low rate of statins intake is noted. The obtained specifics witness for the necessity to optimize AHT among the high and very high risk patients — inhabitants of Tyumenskya oblast.

scholarly journals Thrombosis and Risk of Mortality in Newly Diagnosed High-Risk Polycythemia Vera: An Analysis of the Medicare Claims Database in the United States

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Naveen Pemmaraju ◽  
Aaron T. Gerds ◽  
Shreekant Parasuraman ◽  
Jingbo Yu ◽  
Anne Shah ◽  
...  
Keyword(s):  
High Risk ◽  
Median Time ◽  
Research Funding ◽  
Index Date ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
History Of

Background Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with an increased risk of thrombotic events (TEs), a major cause of morbidity and mortality. Patients aged ≥60 years and/or with a history of thrombosis are considered to have high-risk PV. There is limited contemporary, real-world evidence exploring the effect of TEs on mortality in patients with PV. The aim of this analysis was to compare the risk of mortality in patients newly diagnosed with high-risk PV who experienced a TE vs those who did not experience a TE. Study Design and Methods All data from the Medicare Fee-for-Service (FFS) claims database (Parts A/B/D) from January 2010-December 2017 were used to identify patients with a PV diagnosis (all high risk based on cohort being ≥65 years of age) with ≥1 inpatient or ≥2 outpatient claims. The index date was the date of the first qualifying PV claim. Patients with a PV diagnosis or use of cytoreductive therapy within 12 months before the index date (pre-index period) were excluded; ≥12-months continuous medical and pharmacy enrollment pre-index dates was required. The study sample was categorized into TE and non-TE groups based on the occurrence of any of the following events during follow-up: deep vein thrombosis, pulmonary embolism, ischemic stroke, acute myocardial infarction, transient ischemic attack, peripheral arterial thrombosis, or superficial thrombophlebitis. TEs were evaluated from the index date to the end of follow-up. Cox regression analyses with time-varying effects were used to assess mortality risk among patients with PV, with post-index TE as a time-dependent variable, stratified by pre-index TE, and adjusting for patient demographic characteristics and comorbid conditions. Results A total of 56,176 Medicare FFS beneficiaries with PV diagnoses met inclusion criteria. The median age was 73 years, 51.9% were men, and 90.7% were white; 10,110 patients (18.0%) had a history of TE before diagnosis (ie, pre-index). In the follow-up period, 20,105 patients (35.8%) had a TE and 36,071 patients (64.2%) did not have a TE. In the comparison between the TE vs non-TE groups, the median (range) age (75.0 [65-104] vs 73.0 [65-106] years, respectively), mean (SD) Charlson comorbidity index score (3.1 [2.6] vs 2.2 [2.3]), and percentage of patients with a history of cardiovascular events (34.1% vs 23.8%), bleeding (13.3% vs 10.4%), or anemia (28.6% vs 23.4%) were higher (Table 1). Among all patients with PV, the median time from diagnosis to first post-index TE was 7.5 months. Among those with pre-index TE (n=10,093), median time from index to first post-index TE was 0.6 months, whereas patients without pre-index TE (n=46,083) had a median time to first post-index TE of 14.2 months. Among all patients with TE during follow-up, the most common TEs were ischemic stroke (47.5%), transient ischemic attack (30.9%), and acute myocardial infarction (30.5%). The risk of mortality was increased for patients who experienced a TE compared with those who did not (hazard ratio [HR; 95% CI], 9.3 [8.4-10.2]; P&lt;0.0001). For patients who experienced a pre-index TE, the risk of mortality was increased for patients who experienced a subsequent TE during follow-up compared with patients who did not (HR [95% CI], 6.7 [5.8-7.8]; P&lt;0.0001). Likewise, for patients who did not experience a pre-index TE, the risk of mortality was increased for patients who experienced a TE during follow-up compared with patients who did not (HR [95% CI], 13.1 [11.4-15.0]; P&lt;0.0001). Conclusions In this real-world study, approximately one-third of patients with newly diagnosed high-risk PV experienced a TE during follow-up and had a 9-fold increased risk of mortality vs those who did not experience a TE. TE risk mitigation remains an important management goal in patients with PV, particularly in those with prior TE. Disclosures Pemmaraju: Samus Therapeutics: Research Funding; Celgene: Honoraria; SagerStrong Foundation: Other: Grant Support; Affymetrix: Other: Grant Support, Research Funding; MustangBio: Honoraria; Blueprint Medicines: Honoraria; LFB Biotechnologies: Honoraria; Plexxikon: Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Stemline Therapeutics: Honoraria, Research Funding; Pacylex Pharmaceuticals: Consultancy; Daiichi Sankyo: Research Funding; Incyte Corporation: Honoraria; Roche Diagnostics: Honoraria; Cellectis: Research Funding; DAVA Oncology: Honoraria. Gerds:Sierra Oncology: Research Funding; Celgene: Consultancy, Research Funding; Gilead Sciences: Research Funding; Imago Biosciences: Research Funding; Pfizer: Research Funding; CTI Biopharma: Consultancy, Research Funding; Roche/Genentech: Research Funding; Apexx Oncology: Consultancy; AstraZeneca/MedImmune: Consultancy; Incyte Corporation: Consultancy, Research Funding. Parasuraman:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Yu:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Shah:Avalere Health: Current Employment. Xi:Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation; Avalere Health: Current Employment. Kumar:Avalere Health: Current Employment; Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Verstovsek:Gilead: Research Funding; Incyte Corporation: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; CTI Biopharma Corp: Research Funding; Promedior: Research Funding; Roche: Research Funding; AstraZeneca: Research Funding; Blueprint Medicines Corp: Research Funding; Genentech: Research Funding; Sierra Oncology: Consultancy, Research Funding; Protagonist Therapeutics: Research Funding; ItalPharma: Research Funding; PharmaEssentia: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding.

Risk-adapted therapy utilizing upfront brentuximab vedotin (Bv) and rituximab (R) with reduced toxicity chemotherapy in children, adolescents, and young adults with Hodgkin lymphoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10532-10532
Author(s):  
Jessica Hochberg ◽  
Liana Klejmont ◽  
Lauren Harrison ◽  
Allyson Flower ◽  
Quihu Shi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Hodgkin Lymphoma ◽  
Combination Chemotherapy ◽  
Early Response ◽  
Brentuximab Vedotin ◽  
Response To Therapy ◽  
Newly Diagnosed ◽  
Risk Patients

10532 Background: Cure rates for CAYA patients with Hodgkin Lymphoma remain high, however are limited by significant toxicity of chemoradiotherapy. Brentuximab Vedotin and Rituximab have shown efficacy in relapsed HL. We hypothesize that the addition of both to combination chemotherapy will be safe in newly diagnosed HL preserving current EFS with elimination of more toxic chemoradiotherapy. Objective: To evaluate the safety and overall response and EFS of Brentuximab and Rituximab in combination with risk adapted chemotherapy in CAYA with newly diagnosed HL. Methods: Age 1-30 yrs with newly diagnosed classical HL given 3 to 6 cycles of chemoimmunotherapy: Brentuximab vedotin with Doxorubicin, Vincristine, Prednisone and Darcarbazine (Bv-AVPD) for Low risk patients or Doxorubicin, Vinblastine, Darcarbazine and Rituximab (Bv-AVD-R) for Intermediate/High risk. Early response measured by PET/CT scan following 2 cycles. Slow responders received an additional 2 cycles of Bv-AVD-R for Intermediate Risk or Ifosfamide/Vinorelbine for High Risk patients. Radiation therapy was given ONLY to those patients not in CR. Results: Total = 19 patients. Median age = 15yr (range 4-23yr). Risk = 2 low, 13 intermediate, 4 high. Toxcity = 1 episode of GrIII mucositis, 1 episode of GrIII infusion reaction to Brentuximab. 17 patients have completed therapy. All 17 patients achieved a complete response to therapy for a CR = 100%. Eleven (58%) have achieved a rapid early response. No patient has required radiation therapy. For 17 patients who have completed therapy, the EFS and OS is 100% with a median follow up time of 915 days (30 months). Conclusions: The addition of Brentuximab vedotin and Rituximab to combination chemotherapy for newly diagnosed Hodgkin Lymphoma appears to be safe. Our early results show significant promise with a CR rate of 100% and 58% rapid early response. We have successfully deleted toxic alkylator, topoisomerase inhibitor, bleomycin and radiation from this treatment regimen. The EFS/OS to date is 100% with a median follow up time of 2.5 years. Further follow up and a larger cohort is needed to determine long term outcomes of this approach. Clinical trial information: NCT02398240.

Characteristics and Treatment Response of Newly Diagnosed Advanced-Stage and Relapsed/Refractory Hodgkin Lymphoma in Taiwan: A Nationwide Retrospective Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-30
Author(s):  
Chieh-Lin Jerry Teng ◽  
Tran-Der Tan ◽  
Yu-Wen Lin ◽  
Pei-Wen Lien ◽  
Hsin-Chun Chou ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Outcomes ◽  
Clinical Features ◽  
Advanced Stage ◽  
Stage At Diagnosis ◽  
Newly Diagnosed ◽  
First Line ◽  
Stage Disease ◽  
Risk Patients

Background Hodgkin lymphoma (HL) is a highly curable hematological neoplasm, even in an advanced stage. However, despite improvements in treatment, patients with primary refractory and/or relapsed HL (RRHL) still have a poor prognosis. Because of relatively low incidence, studies focusing on the clinical characteristics or outcomes for patients with advanced-stage HL and RRHL in Asia are few. The present study aimed to describe the clinical features and survival of these patients in Taiwan using a nationwide database. Methods This retrospective descriptive study was conducted by using the Taiwan Cancer Registry and the National Health Insurance Research Database. All newly diagnosed HL patients who started frontline treatment with an intent to cure were enrolled from 2009 to 2016. Patients who had an advanced-stage disease (i.e., stage III/IV) at diagnosis were identified. All chemotherapy agents prescribed during the 60-day period after the date of first treatment were considered as the same line regimen. Patients with RRHL were identified as those receiving a new chemotherapy for HL (across stages) other than the first-line regimen or undergoing an autologous stem cell transplantation (ASCT) at any time. We described the first-line regimens for newly diagnosed advanced-stage HL and salvage therapy for RRHL. Characteristics and survival outcomes, including overall survival (OS) and time to next treatment (TTNT, as a surrogate for progression-free survival, PFS), were further analyzed for patients who received ABVD or ABVD-like (BVD and AVD) regimen as the first-line treatment, specifically in those with advanced stage at diagnosis and RRHL patients who received ASCT. Results Between 2009 and 2016, 1,156 newly diagnosed HL patients with an intent-to-cure treatment were enrolled; of whom 490 were advanced stage at diagnosis. A bimodal age distribution with peaks around 20-44 and after 65 years was observed. Among the patients with an advanced stage disease, ABVD was the dominant frontline regimen, accounting for 79% of treated HL cases, followed by ABVD-like regimens (15%), and BEACOPP (3%). The median age of patients receiving ABVD/ABVD-like regimen was 34 years, and 62% were male. Over half of the patients were stage IV (57%), having extra-nodal disease (58%), and/or B-symptoms (54%). Only 19% of them received radiotherapy along with chemotherapy. With a median follow-up of 4.7 years, the OS and PFS rates were 76% and 52%, respectively. Among 321 RRHL patients, 288 had received ABVD/ABVD-like regimens as frontline therapy. In this 288-patient cohort, 135 (47%) proceeded to ASCT. Among these 135 patients, ESHAP was the commonest salvage therapy (62%), followed by ICE (15%), and others (7%). After a 3.9-year median follow-up, the OS and PFS rates were 76% and 47%, respectively. Discussion The current study describes the clinical characteristics and treatment outcomes of patients with advanced-stage HL and RRHL in Taiwan. Prior studies describing clinical features and outcomes of HL patients in Taiwan are limited to a single medical center experience. Our study provides nationwide data and suggests the clinical features of advanced-stage HL patients are not much different from those in Western countries. Though the OS of advanced-stage HL remained high, half of the patients who received standard treatment developed relapsed/refractory disease, suggesting a strong unmet need for better novel therapies. Among the RRHL patients receiving ASCT, about half of them experienced further disease progression, and a quarter died afterwards. This observation highlights the importance of identifying high-risk patients for progression. Moreover, regimens that include novel agents may improve the outcomes of early high-risk patients. Further studies are needed to determine the real-world treatment outcomes and cost-effectiveness of these novel agents. Conclusion The characteristics of advanced-stage HL in Taiwan were comparable to those in Western countries. Considering the poor prognosis of RRHL, it is crucial to identify patients with a high risk of progression in the first line so that we can optimize their treatment outcomes. Disclosures Lien: Takeda Pharmaceuticals Taiwan: Ended employment in the past 24 months. Chou:Takeda Pharmaceuticals Taiwan: Current Employment. Lin:Takeda Pharmaceuticals Taiwan: Research Funding.

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