Short Progression Free Survival Predicts for Poor Overall Survival In Older Patients with Multiple Myeloma Treated Upfront with Novel Agent-Based Therapy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3035-3035
Author(s):  
Efstathios Kastritis ◽  
Maria Roussou ◽  
Maria Gavriatopoulou ◽  
Magdalini Migkou ◽  
Maria Gkotzamanidou ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Fold Increase ◽  
Novel Agents ◽  
Agent Based ◽  
Early Relapse ◽  
Factors Associated ◽  
Platelet Counts ◽  
Poor Outcome ◽  
Depth Of Response ◽  
Novel Agent

Abstract Abstract 3035 Data from patients with multiple myeloma (MM) treated with autologous transplantation indicate that a short remission period after high dose therapy, usually less than 12 months, is associated with a poor outcome and limited efficacy of salvage regimens. Also, failure to respond to upfront thalidomide or lenalidomide based-regimens is associated with poor outcome. However, such data are limited for the general, unselected population of elderly or non-transplant treated MM patients, especially after the introduction of novel agents in the upfront treatment of myeloma. Thus, we analyzed the outcome of 115 unselected patients, who were older than 65 years and who were treated upfront with novel agent-based regimens in a single center in Athens, Greece. Many of these patients had been included in clinical trials; however, several patients who were ineligible because of poor performance status, significant renal impairment or comorbidities were also treated with novel agent-based regimens. Thus, these patients are more representative of the general myeloma population. IMWG criteria were used for the assessment of response, progression-free (PFS) and overall survival (OS). Forty three percent of patients were >75 years. Nine percent died within 3 months from initiation of treatment. Among 106 patients who survived for at least 3 months, 77% achieved an objective response: 20% achieved a CR, 26% a VGPR and 33% a PR. On an intention to treat, 58% of patients have progressed so far. Among patients who responded to initial treatment, 19% who had achieved a CR, 27% who had achieved a VGPR and 37% who had achieved a PR, relapsed(p=0.012). At the time of relapse or progression, patients were treated again with novel agents. Median PFS for all patients was 21 months (95% CI: 18–23 months), while median PFS for patients who achieved CR/VGPR or PR as best response was 20 months and 22 months, respectively (p=0.9). Subsequently, we analyzed 94 patients who started treatment at least 12 months before this analysis. Among these patients, 32% had a PFS shorter than 12 months including 26% of patients who initially responded. Depth of response was predictive of probability for early relapse: CR 5%, VGPR 29% and PR 38% (p=0.04). In the univariate analysis, LDH ≥300 IU/L (upper limit of normal 225 IU/L) was the only factor associated with shorter PFS while other factors such as ISS stage, age >75 years, Hb <10 g/dl, platelet counts <130,000/ml) did not affect PFS. The probability for two-year OS for patients who achieved a CR was 93%, for patients with VGPR was 69% and for patients who achieved a PR was 83% (p=0.188). Baseline factors associated with poor OS in the univariate analysis, included age >75 years (median OS of 28 months vs. 62 for patients younger than 75 years, p<0.001), hemoglobin <10 g/dl (p=0.05), platelet counts <130,000/ml (p=0.012), ISS stage (p=0.031) and elevated LDH (p<0.001). Furthermore, patients who relapsed or progressed within the first 12 months had a median survival of 18 months compared to a median survival of 53 months for patients who relapsed after at least 12 months from treatment initiation (p<0.001). In the multivariate analysis, PFS <12 months was the most significant adverse prognostic factor associated with a 12.7 (95% CI 5–33) fold increase in the risk for death. Other factors associated with poor survival were elevated LDH ≥300 IU/L (HR=10.7, p=0.001), age >75 years (HR=5.37, p<0.001), baseline platelet counts <130,000/ml (HR=4.65, p=0.001) and ISS-3 (HR=3, p=0.007). In conclusion, in elderly patients (‘65 years) who are treated upfront with novel agents, short PFS (less than 12 months) is associated with a very poor outcome and a more than 12 –fold increase in the hazard of death. Probably due to the limited number of patients, we did not observe a statistically significant correlation of the depth of response with OS. However, a significantly lower percentage of patients who had achieved a CR experienced an early relapse. Our data indicate that salvage treatments for patients who fail to respond or progress early after frontline therapy with novel agent-based regimens may not be effective and new drugs and treatment strategies are needed. These patients should be encouraged to participate in clinical trials which investigate experimental agents and combinations. Disclosures: Dimopoulos: Ortho-Biotech: Honoraria; Celgene: Honoraria; Millennium: Honoraria.

Elevated Serum Lactate Dehydrogenase (LDH) Should Be Included Among the Variables Which Define High Risk Multiple myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2969-2969
Author(s):  
Meletios A. Dimopoulos ◽  
Efstathios Kastritis ◽  
Maria Roussou ◽  
Maria Gkotzamanidou ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Renal Impairment ◽  
Elevated Serum ◽  
Novel Agents ◽  
Serum Lactate Dehydrogenase ◽  
Agent Based ◽  
Poor Outcome ◽  
Novel Agent

Abstract Abstract 2969 LDH is elevated in approximately 10% of patients with newly-diagnosed, symptomatic, multiple myeloma (MM). In patients treated with conventional chemotherapy, elevated LDH is associated with poor outcome (Dimopoulos et al, Ann Intern Med 1991). In selected patients treated with combinations of novel agents and tandem transplantation, LDH is an independent prognostic factor and is associated with short event free and overall survival even when cytogenetic abnormalities and gene expression signature are considered (Barlogie et al, J Clin Oncol 2010). An analysis from our group has also suggested that LDH improves the prognostic value of the International Scoring System (ISS) for MM (Terpos et al, Eur J Hematol 2010). However, there is limited data about the prognostic importance of elevated LDH in unselected MM patients who have been treated upfront with novel agent-based regimens. To address this issue, we analyzed 180 consecutive, unselected patients from a single center in Athens, Greece, who were treated upfront with novel agent (thalidomide, bortezomib or lenalidomide)-based therapies. Many of these patients had been included in clinical trials; however, several patients who were ineligible because of poor performance status, significant renal impairment or comorbidities were also treated with novel agent-based regimens. Thus, these patients are more representative of the general myeloma population. Fifty-one per cent of our patients were older than 70 years of age. LDH was elevated (≥300 IU/L, upper limit of normal 225 IU/L) in 8% patients before initiation of treatment. Elevated LDH was associated with features of advanced disease such as ISS-3 stage (p=0.063) and impaired renal function (p=0.034). The objective response rate in patients with elevated LDH was 47% and in patients without elevated LDH was 79% (p=0.011). The median overall survival for all patients was 54 months. Elevated LDH was associated with poor outcome (median survival 21 months vs. 56 months for patients with LDH <300 IU/L, p=0.007). Other factors which were associated with inferior survival, in the univariate analysis were age >70 years (p<0.001), Hb <10 g/dl (p<0.001), platelet counts <130,000/ml (p<0.001), corrected serum calcium >11.5 g/dl (p=0.012), ISS-3 stage (p<0.001) and renal impairment (p=0.001). In the multivariate analysis, elevated serum LDH was an independent factor and had a major prognostic impact associated with a 5.4-fold increased risk for death (p<0.001). Furthermore, elevated serum LDH was more often associated with early death. We conclude that in unselected MM patients treated upfront with novel agents, serum LDH is a simple, inexpensive and readily available blood test, which identifies a subset of patients with poor outcome. Our data suggest that in future phase 3 trials, LDH should be taken into account for the stratification of patients. Furthermore, elevated baseline serum LDH should be included in the current criteria (i.e. poor risk cytogenetics, high plasma cell labeling index) which are being used to characterize high risk myeloma. Disclosures: No relevant conflicts of interest to declare.

Upfront Treatment with Novel Agents Improves the Survival of Symptomatic Patients with Multiple Myeloma Who Are Older Than 65 Years

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1947-1947
Author(s):  
Meletios A. Dimopoulos ◽  
Efstathios Kastritis ◽  
Maria Roussou ◽  
Maria Gavriatopoulou ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
General Population ◽  
Renal Impairment ◽  
Performance Status ◽  
Novel Agents ◽  
Agent Based ◽  
Risk Of Death ◽  
Group A ◽  
Group B ◽  
Novel Agent

Abstract Abstract 1947 The introduction of novel agents and improvements in supportive care over the last years resulted in a significant improvement of the overall survival (OS) of myeloma patients (Brenner et al Blood 2008, Kumar et al Blood 2008, Kastritis et al Leukemia 2009). However, these retrospective studies indicated that this survival benefit was more pronounced in younger patients while in older patients there was only a marginal improvement in outcome. Randomized studies have shown that upfront use of thalidomide with melphalan and prednisone (MPT) offers superior progression free survival (PFS) than MP alone, and in some of these studies there was also a survival advantage. Bortezomib with MP was also superior to MP in a randomized study, both in terms of PFS and OS. However, these studies included selected patients that may not be representative of the general population of elderly patients with myeloma. Thus, we analyzed our database in order to assess the effect of the upfront use of novel agents (thalidomide, bortezomib, lenalidomide) in consecutive patients older than 65 who were treated in a single center, in Athens, Greece. Many of these patients had been included in clinical trials; however, several patients who were ineligible because of poor performance status, significant renal impairment or comorbidities were also treated with novel agent-based regimens. Thus, these patients are more representative of the general myeloma population. We included patients who started treatment from January 1995 to January 2010, i.e patients who received similar supportive care. All patients were included in the analysis, regardless of performance status, infections, comorbidities etc. Patients were divided in two groups: those who were treated upfront with conventional regimens (group A, N=76) and those who were treated upfront with novel agent-based regimens (group B, N=115). Demographics of the two groups of patients, including gender and age were similar. Performance status at presentation was also similar among the two groups: 56% of those treated upfront with conventional agents and 57% of those treated upfront with novel agents had an ECOG performance status of 2 or higher. Thirty per cent of patients in group A and 44% of patients in group B were older than 75 years, respectively (p=0.07). The presence of osteolytic bone disease (p=0.313), anemia (Hb <10 g/dl, p=0.139), low platelets (<130,000/ml, p=0.949), albumin <3.5 g/dl (p=0.661), elevated LDH ≥300 IU/L (p=0.412), levels of Bence Jones proteinuria (p=0123), heavy (p=0.220) and light chain isotype (p=0.837) were similar among the two groups. However, patients treated upfront with novel agents presented more often with renal impairment (creatinine ≥2 mg/dl in 29% vs. 16%, p=0.044) and had more often elevated beta2-microglobulin levels (p=0.046) and ISS-3 disease (49% vs. 32%, p=0.1). Response to first line treatment was similar for the two groups: 73% for patients treated with novel agents vs. 67% for patients treated with conventional regimens (p=0.371). The median survival of the patients who were treated with novel agent-based regimens was 47 months while it was 34 months for those who received conventional regimens, but this was not statistically significant (p=0.271). Early death rates (<3 months from the initiation of treatment) were 8% for those treated upfront with novel agents and 11% for those treated with conventional regimens. After adjustment for adverse prognostic factors, such as elevated beta2-microglobulin, renal impairment and advanced age, upfront use of novel agents was associated with a significant reduction in the risk of death (HR=0.621, p=0.029). Subsequently, we performed a multivariate analysis which included established adverse prognostic factors and the upfront use of novel drugs. In this analysis, upfront treatment with novel agents was independently associated with superior outcome and a reduced risk of death (HR=0.626, p=0.033). Other factors independently associated with adverse outcome were ISS stage (ISS-3: HR=2.64, ISS-2: HR=1.25, p=0.032), elevated LDH ≥300 IU/L (HR=3.5, p=0.002) and low platelet counts <130,000/ml (HR=1.68, p=0.038) and age >75 years (HR=2, p=0.002). We conclude that in the general population of elderly patients with MM the upfront use of novel agents is associated with improved survival. Disclosures: Dimopoulos: Ortho-Biotech: Honoraria; Celgene: Honoraria; Millennium: Honoraria.

scholarly journals Racial Disparity in Patients with Multiple Myeloma Are Blunted in the Era Novel Therapies

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2525-2525
Author(s):  
Leon Bernal-Mizrachi ◽  
Ajay K Nooka ◽  
Chandra Pooja ◽  
Monica S Chatwal ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Research Funding ◽  
Response Rate ◽  
Univariate Analysis ◽  
Novel Agents ◽  
Factors Associated ◽  
Indolent Disease ◽  
The Impact ◽  
White Patients

Abstract Background: Multiple myeloma is the most common hematological malignancy among african americans (AA). Prior studies have shown conflicting results for outcomes based upon ethnicity following autologous stem cell transplantation (ASCT). However, much of this data is older, and predates the use of novel agents such as bortezomib (V), lenalidomide (R) and thalidomide (T). Methodology: We performed a retrospective analysis of 292 patients (147 AA and 145 Caucasian) treated with novel agents (proteasome inhibitors or immune modulators) and ASCT from 2006 to 2012 at the Winship Cancer Institute of Emory University to evaluate the impact of ethnicity on outcomes. Results: Baseline characteristics such as stage (International Staging System, ISS), presence of lytic lesions or plasmacytomas, immunoglobulin subtype, and cytogenetic risk category at presentation, were comparable between AA and white patients. Among AA, 112 (76.19%) patients received bortezomib containing regimens (VRD: 34.8%, VTD: 22.3%, VDTPACE:11%, VDD:10%, VD:19% and others bortezomib regimens 8%), 54 (36.7%) patients received lenalidomide (VRD: 34.8% or RD: 11.6%) and 72 (49%) patients received thalidomide (VTD: 22.3% or TD: 11.6%). In white patients 113 (77.93%) received bortezomib containing regimens (VRD: 33.1%, VTD: 17.2%, VDTPACE:9.6%, VDD: 1.4% and VD:11.7% and other bortezomib regimens 1.3%), 69 (47.6%) patients received lenalidomide containing regimens (VRD:33.1% and RD:11%) and 62 (42.8%) patients received thalidomide containing regimens (VTD: 17.2% or TD: 15%). A higher percentage of patients in the white cohort carried the antecedent diagnosis of monoclonal gammopathy in white patients (AA:0 vs white: 4.8%, p=0.007), and as expected, AA patients presented at a younger age when compared with whites (mean age of 55 vs 59 years, respectively, p<0.001). The overall response rate (ORR) of induction in the entire population was 86%, with an >VGPR of 58.8%. No difference was identified in pre-transplant ORR and >VGPR between AA (87.9% and 25.9%, respectively) and white patients (81.54% and 22.4%, respectively, p>0.1). Similarly, the ORR and >VGPR 100 days after transplantation was comparable between both ethnic groups (AA: OR:90.74% and >VGPR:74.07% vs white OR:90.65% and >VGPR: 77.57%, p>0.1). The depth of response after ASCT improved similarly in both groups (AA: 57.3% vs white: 67.7%, p=0.1). When the overall survival and progression free survival where evaluated, we found no significant differences between both cohorts. Factors associated with longer PFS in the population studied include AA race and the introduction of lenalidomide in the induction regimen. In AA patients univariate analysis identified early stage at presentation, indolent disease (prolong time from diagnosis to transplant), optimal pre-transplant response, and pre-transplant use of lenalidomide (HR:0.38 (0.18-0.8), p=0.01) as factors that potentially prolong PFS. Multivariate analysis identified the use of lenalidomide, as part of the pretransplant regimen, to reduce the risk of relapse (HR:0.38 (0.18-0.8), p=0.01) compared to bortezomib use (HR: 5.3 (2.11-11.98), p<0.001). In white patients, univariate and multivariate analysis identified that IgG and kappa light chain MM and indolent disease were factors associated with longer PFS, while history of plasma cell leukemia was related to shorter PFS. In conclusion, our results showed that novel agents have improved the response rate of both ethnic populations. From our preliminary analysis, it appears the PFS is longer among AA patients, suggesting a potential difference in MM biology of this patient population. Disclosures Lonial: Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.

The Impact of Induction Regimen Choice on Transplant Outcome and Survival in Newly Diagnosed Multiple Myeloma in the Era of Novel Agents

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3044-3044
Author(s):  
Rajshekhar Chakraborty ◽  
Shaji Kumar ◽  
Francis Buadi ◽  
David Dingli ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Research Funding ◽  
Novel Agents ◽  
Agent Based ◽  
Induction Regimen ◽  
Baseline Characteristics ◽  
The Impact ◽  
Novel Agent

Abstract Background Induction with novel agents, including proteasome inhibitors and immunomodulators, prior to autologous stem cell transplantation (ASCT) is the standard of care frontline treatment of transplant-eligible patients with multiple myeloma (MM). Common novel agent-based induction regimens include three drug combinations with a backbone of bortezomib (V), thalidomide (T) and/or lenalidomide (R). There is limited information on the comparative efficacy of novel regimens used as part of initial therapy prior to an ASCT in terms of overall survival (OS). To address this question, we retrospectively analyzed 1096 consecutive patients undergoing ASCT for MM at Mayo Clinic. Methods Study patients included those who underwent first transplant within 12 months of diagnosis, did not receive more than one induction regimen, did not relapse prior to transplant and did not receive treatment for smoldering MM in the past. Baseline characteristics, response rates and survival data were extracted from an electronic medical record and statistical analysis was done using JMP 10.0.0 (SAS Institute Inc.). Choice of induction regimen was almost exclusively made by the referring physician. Results Median age at diagnosis was 60.3 years (Interquartile range 53.9-65.9). ISS staging at diagnosis was available for 49.7% of patients, of which, 34.2%, 39.3% and 26.5% of patients had ISS stage 1, 2 and 3 disease, respectively. Estimated median follow up was 65.6 months (95% CI 58.3-73.3). Baseline characteristics of patients by initial treatment have been summarized in table 1. Major subgroups by induction therapy included patients receiving Cy-Bor-d (n=193, 17.6%), Vd (n=64, 5.83%), Rd (n=253, 23.1%), VRd (n=126, 34.6%), Td (n=157, 14.3%) and VAD or dexamethasone alone as the non-novel agent comparator group (n=229, 20.9%). Median overall survival (OS) was significantly different between novel agent-based and conventional regimens (Log-rank test; p=0.0029), which were 102.7 months (95% CI, 95.2-112.2) and 78.8 months (95% CI, 67.8-92.6) respectively. Median OS with each regimen is shown in table 1. Among novel agent-based regimens, there was no significant difference in median OS, except Td, which was inferior to Rd (HR 1.62; 95% CI 1.17-2.24). Conclusion We cannot demonstrate with overall survival as an endpoint that the doublets of Vd and Rd are inferior to VRd or Cy-bor-d. There were insufficient patients treated with VTd to be included. Our study shows that the choice of novel induction regimen prior to ASCT does not affect survival (with the exception of Td being inferior to Rd), reflecting the wide array of effective salvage options. However, further prospective randomized clinical trials comparing these regimens are required to validate these findings. Table 1. Baseline characteristics and overall survival. Baseline characteristics and survival Cy-Bor-d (n=193) Vd (n=64) Rd (n=253) VRd (n=126) Td (n=157) VAD or Dex (n=229) p-value Median age 61.9 62.15 60.8 60.8 59.3 58.5 0.0041 Sex (percent males) 56.48 57.81 56.92 61.91 57.96 59.82 0.9271 ISS at diagnosis 1:24.82% 2:40.69% 3:34.48% 1:29.73% 2:24.32% 3:45.94% 1:40% 2:43.78% 3:16.22% 1:41.76% 2:34.06% 3:24.18% 1:28% 2:36% 3:36% 1:20% 2:60% 3:20% 0.0005 Median follow-up (95% CI) 20.3 (17.1-22.7) 49.5 (44.7-55.7) 59 (54.5-67) 26.9 (22.8-30.7) 126.7 (120.2-132.9) 143.4 (132.5-152.6) <0.0001 Median OS Not reached (Estimated 5 year OS rate 75%) 97.2 months (95% CI, 66.6-NR) 112 months (95% CI, 97.4-124.3) Not reached (Estimated 5-year OS rate 77%) 81.1 months (95% CI, 59.1-99.1) 78.8 months (95% CI, 67.8-92.6) 0.0019 Figure 1. Figure 1. Disclosures Kumar: Onyx: Consultancy, Research Funding; Novartis: Research Funding; Abbvie: Research Funding; Celgene: Consultancy, Research Funding; Millenium: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Gertz:Smith Kline: Honoraria; Novartis: Honoraria; Onyx: Honoraria; millenium: Consultancy, Honoraria; Celgene: Honoraria.

Abstract 9: Predictors of Poor Outcome in Patients Not Thrombolysed Due to Mild or Resolving Symptoms ("Too Good To Treat")

2014 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Syed F Ali ◽  
Urooba Faheem ◽  
Aneesh B Singhal ◽  
Anand Viswanathan ◽  
Scott B Silverman ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Time Frame ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Factors Associated ◽  
Poor Outcome ◽  
Poor Outcomes ◽  
Iv Tpa

Introduction: A common reason for exclusion of patients with acute ischemic stroke presenting within the time frame for IV tPA is that they are “too good to treat” due to rapidly improving or mild symptoms. Several studies have reported poor outcomes in this group which motivated us to evaluate patient factors associated with poor outcomes. Methods: Using our institutional GWTG database, we analyzed 2,745 consecutive stroke admissions (01/2009 - 07/2013). Univariate and multivariable analysis were carried out to determine factors associated with poor outcome, defined as not being discharged home. Results: Of the total 2,745 patients, 306 (11.1%) presented within the window for IV tPA but did not receive the treatment due to symptoms too mild or rapidly improving as judged by the treating team. Of these 306, 64.1% were discharged home, 26.5% to IRF, 7.2% to SNF and 2.9% expired/hospice. Patients with poor outcome were older, more frequently Hispanic and presented with more vascular risk factors such as hypertension, diabetes, CAD, PAD and atrial fibrillation than good outcome patients. They also had higher median initial NIHSS. Patients in both groups had similar adherence to early antithrombotics, dysphagia screening and DVT prophylaxis. Poor outcome patients had higher rates of in-hospital complications and a longer hospital length of stay (Table 1). On univariate analysis, factors associated with poor outcome included age [OR 1.50 (1.30 - 1.70), p<0.0001], ethnicity [4.15 (1.25 - 13.81), p=0.020], diabetes mellitus [1.91 (1.11 - 3.29), p=0.019], atrial fibrillation [1.82 (1.02 - 3.25), p=0.042], PAD [9.02 (1.04 - 78.20), p=0.046], NIHSS [1.16 per point (1.06 - 1.27), p=0.001], in-hospital pneumonia (all cases had poor outcome) or UTI [7.04 (1.92 - 25.81), p=0.003]. In multivariable analysis, only age [1.50 (1.30 - 1.70), p<0.0001], ethnicity [6.61 (1.83 - 23.85), p=0.004], NIHSS [1.14 per point (1.04 - 1.26), p=0.007] and UTI [7.30 (1.72 - 31.00), p=0.007] remained significant. Conclusion: A substantial percentage of patients deemed “too good” for IV tPA were unable to be discharged home. Factors such as advanced age and higher NIHSS should be considered in tPA decision-making to optimize outcomes. Large, multi-center prospective studies are underway to study the predictors of poor outcomes in this group.

scholarly journals Risk factors associated with bleeding after prophylactic endoscopic variceal ligation in cirrhosis

Endoscopy ◽  
2020 ◽  
Author(s):  
Andreas Drolz ◽  
Christoph Schramm ◽  
Oliver Seiz ◽  
Stefan Groth ◽  
Eik Vettorazzi ◽  
...  
Keyword(s):  
Platelet Count ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Fold Increase ◽  
Bleeding Complications ◽  
Endoscopic Variceal Ligation ◽  
Safe Procedure ◽  
Bleeding Events ◽  
Factors Associated ◽  
Grade Iii

Background Prophylactic endoscopic variceal band ligation (EVL) is frequently performed in patients with liver cirrhosis. The aim of our study was to identify factors associated with early upper gastrointestinal bleeding (UGIB) in cirrhosis patients after prophylactic EVL. Methods 787 nonemergency EVLs performed in 444 patients in two German University medical centers were analyzed retrospectively. Results Within 30 days after EVL, 38 UGIBs were observed (4.8 % of all procedures). Bilirubin levels (hazard ratio [HR] 1.5, 95 % confidence interval [CI] 1.2–2.0 for a 2-fold increase) and presence of varices grade III/IV according to Paquet (HR 2.6, 95 %CI 1.3–5.0 compared with absence or smaller sized varices) were independently associated with UGIB following EVL. International normalized ratio (INR) was associated with bleeding events in the univariate analysis but did not reach statistical significance after adjustment for bilirubin and presence of varices grade III/IV (HR 1.2, 95 %CI 0.9–1.6 for an increase by 0.25). There was no statistically significant association between platelet count or fibrinogen levels and UGIB. Substitution of coagulation products did not affect incidence of bleeding after EVL, which also applied to patients with “coagulopathy” (INR > 1.5 and/or platelet count < 50 × 109/L). No association between proton pump inhibitor therapy and post-EVL UGIB was observed. Conclusions EVL is a safe procedure and immediate bleeding complications are rare. Serum bilirubin levels and size of varices, rather than coagulation indices, are associated with UGIB after EVL. Our data do not support the preventive substitution of blood or coagulation products.

Outcomes of Elderly cHL Patients in the Novel Agent Area: Improved Survival Since 2011 in the SEER-Registry Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-4
Author(s):  
Harsh Shah ◽  
Seongho Kim ◽  
Hyejeong Jang ◽  
Ahmad S Halwani
Keyword(s):  
Risk Factors ◽  
Sensitivity Analysis ◽  
Age At Diagnosis ◽  
Novel Agents ◽  
Stage Iii ◽  
The Novel ◽  
Factors Associated ◽  
Registry Analysis ◽  
Novel Agent

Background: Classical Hodgkin Lymphoma (cHL) patients that are older than 60 years have worse survival compared to those that are younger due to aggressive biology and treatment-related toxicities. Approval of novel agents such as brentuximab (2011) and checkpoint inhibitors (2016) in the relapsed/refractory setting has changed the treatment paradigm of cHL. To assess the effect of novel therapeutic agents on the survival of elderly cHL patients over time, we conducted a SEER 18 registry analysis (released Nov 2018) of cHL patients greater than 60 year old and compared outcomes of those diagnosed between 2006-2010 (before approval of novel agents) to those diagnosed between 2011-2015 (novel agent era). Methods: Patients from SEER 18 registry (released Nov 2018) with cHL and age 60 or greater were included in this study. Cohort 1 included patients from pre-novel agent era (diagnosed from 2006-2010) and cohort 2 included patients from novel agent era (diagnosed from 2011-2015). Last follow-up was available until Dec 2016. Kaplan-Meier estimates were used to summarize the distributions of OS . Univariable and multivariable Cox proportional hazards regression models were fit to assess associations between prior chosen factors (age, sex, race [Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Hispanic (H), Non-Hispanic Asian/Pacific Islander (NH A/P)], stage at diagnosis [I-II vs III-IV], marital status [married vs others], treatment-era [pre-novel agents vs novel agents era] and OS. Sensitivity analysis was explored to adjust the effect of follow-up duration difference between the two cohorts; patients who were in cohort 1 and whose follow-up duration was greater than the maximum follow-up duration of cohort 2 were considered censored at the time of the maximum follow-up duration of cohort 2 Results: There were total of 4957 patients analyzed in this study. In cohort 1 (pre-novel agent era) there were total of 2546 patients, n=1980 (78%) for NHWs, n=309 (12%) for Hs, n=166(7%) for NHBs, n=91(4%) for NH A/PIs; in cohort 2 (novel agent era), there were 2411 patients, n=1761(73%) for NHWs, n=371(15%) for Hs, n=176 (7%) for NHBs, n=103(4%) for NH A/PIs (p=.001) (Table 1). There was no difference in age at diagnosis, marital status, and sex between the two groups. Cohort 2 had more patients with Stage III-IV disease (55% in C2 vs 50% in C1, with p=.002) (Table 1). In the novel agent era, there were more patients who had chemotherapy "Yes" status compared to "No or Unknown" status (73% with "Yes" in Cohort 2 vs 68% with "Yes" in Cohort 1 with p&lt;.001) (Table 1). Cohort 1 had median follow-up of 8.33 years and Cohort 2 had median follow-up of 3.33 years. Cohort 1 had median OS of 4 years (3.58-4.25) years and Cohort 2 had median OS of 4.75 years (4.25-5.67) with HR of .92 (.85-1.00); p=.052 (Figure 1a). Hispanics had worse OS compared to NHWs with HR of 1.24 (1.09-1.40) with p &lt; .001; NHBs had similar OS compared to NHWs with HR of .95 (.79-1.13) with p&gt; .99 (Figure 1b). In the univariable analysis (UVA) to assess risk factors associated with OS, older age at diagnosis, Hispanic race, Stage III-IV and unmarried status were associated with worse OS. In the multivariable (MVA) analysis to assess risk factors associated with OS, older age at diagnosis, male gender, stage III-IV, unmarried status, Hispanic race and pre-novel agent era were associated with worse OS (Table 2). In the sensitivity analysis, HR was for OS was .92 (.85-1.00) with p=.039 for Cohort 2 (novel agent era) compared to Cohort 1 (pre-novel agent era). In the sensitivity analysis, the difference in OS between the NHWs and Hispanics remained; UVA and MVA for risk factors associated with OS remained the same after this adjustment also. CONCLUSION: In this SEER analysis, we found that elderly cHL patients who were diagnosed with cHL after novel agents such as brentuximab and CIs were approved (2011 and after) have improved survival by about 9 months compared to patients diagnosed before the approval of such agents (2006-2010). The improved survival likely reflects better efficacy and tolerability of these agents in elderly population as opposed to cytotoxic chemotherapy options. Lastly, we did not see any difference in survival of NHBs compared to NHWs unlike in previous SEER analysis; however, Hs still had worse OS compared to NHWs. In conclusion, OS of elderly cHL patients is improving in the novel agent era. Disclosures No relevant conflicts of interest to declare.

High Serum Lactate Dehydrogenase (LDH) Is An Important Prognostic Factor in the Era of Novel Agents and Adds to the Prognostic Value of the International Staging System (ISS) in Patients with Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1819-1819
Author(s):  
Dimopoulos A. Dimopoulos ◽  
Maria Roussou ◽  
Anastasia Pouli ◽  
Eirini Katodritou ◽  
Argiris Symeonidis ◽  
...  
Keyword(s):  
Median Survival ◽  
Prognostic Value ◽  
Performance Status ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Elevated Serum ◽  
High Serum ◽  
Serum Lactate Dehydrogenase ◽  
Agent Based ◽  
Novel Agent

Abstract Abstract 1819 Poster Board I-845 Several older studies have shown that high serum LDH is associated with features of advanced disease and with an inferior survival of symptomatic patients with MM who require treatment. It is however unclear whether LDH may add to the prognostic value of ISS and whether it may retain its prognostic significance in patients who have been exposed to novel agent-based therapies either at diagnosis or later in the course of their disease. In order to address these issues we analyzed 996 consecutive symptomatic patients who were included in the data base of the Greek Myeloma Study Group and who received frontline treatment between January 1995 and December 2008. Elevated serum LDH to ≥300 IU/L (normal levels <225 IU/L) was observed in 11% of patients. High LDH was seen more often in patients with impaired performance status (p<0.01), with anemia (p<0.01), with thrombocytopenia (p<0.01), with renal impairment (p<0.01), with high ISS (p<0.01), and with hypercalcemia (p=0.01). The median survival of all patients was 40 months with a clear improvement for patients who started treatment after January 2000 as compared to patients who started treatment before that date (50 months versus 31 months; p<0.01). Multiple clilnical and laboratory variables correlated with the probability of survival in univariate analysis. A multivariate analysis showed that the following variables had an independent prognostic significance: LDH (p<0.001), ISS (p<0.001), performance status (p<0.001), age (p<0.001) and platelet count (p<0.001). The median survival of patients with high versus normal LDH was 15 months versus 44 months (p<0.001). High LDH was observed in 7% of patients with ISS-1, in 10% of ISS-2 and 12% of ISS-3. Within each ISS subgroup the presence of high LDH was associated with a worse median survival. In ISS-1 the median survival of patients with high LDH was 22 months (CI 95%: 10-35) while the median survival of those with normal LDH was 76 months (CI 95%: 61-91; p<0.01). Similarly in ISS-2 the median survival of patients with high and normal LDH was 11 months (CI 95%: 7-14) and 40 months (CI 95%: 32-48), respectively (p<0.001), while in ISS-3 it was 17 months (CI 95%: 11-23) and 27 months (CI 95%: 21-33), respectively (p<0.01). Subsequently, patients were separated into two groups: patients who started treatment between January 1995 and December 1999 and patients who started therapy after January 2000 i.e. patients who had access to novel agent-based therapy. In both groups the presence of high LDH was related with statistically worse survival. In patients who received treatment before January 2000, the median survival in the high LDH group was 10 months (CI 95%: 4-16) versus 36 months in the normal LDH group (CI 95%: 31-42; p<0.001). Similarly, in patients who received treatment after January 2000, the median survival in the high LDH group was 21 months (CI 95%: 12-29) versus 51 months in the normal LDH group (CI 95%: 40-63; p<0.001). We conclude that serum LDH is a readily available and inexpensive variable which has a major impact on the survival of patients with myeloma even when they belong to a low or intermediate ISS subgroup and even when they receive novel agent-based therapy. Disclosures No relevant conflicts of interest to declare.

The Impact of Different Pre-Transplant Regimens Including Novel Agents On Peripheral Blood Mobilization, Harvest, Response and Survival in Patients Undergoing ASCT for Multiple Myeloma. A Single-Center Experience in 210 Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2279-2279
Author(s):  
Evangelos Eleutherakis-Papaiakovou ◽  
Dimitrios Christoulas ◽  
Magdalini Migkou ◽  
Maria Gavriatopoulou ◽  
Maria Roussou ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Response Rate ◽  
Novel Agents ◽  
High Dose ◽  
Agent Based ◽  
Cd34 Cells ◽  
Group A ◽  
Group B ◽  
The Impact ◽  
Novel Agent

Abstract Abstract 2279 Poster Board II-256 High dose therapy (HDT) with autologous stem cell transplantation (ASCT) has become the standard of care for eligible patients with multiple myeloma (MM) younger than 65 years. Induction therapy with combination regimens such as VAD or single agent dexamethasone has little impact on SC mobilization and offers a PFS of 12-18 months post-ASCT. Recently, novel agents (IMiDs and bortezomib) are used in the induction regimens prior to ASCT. The aim of this study was to assess the impact of conventional and novel agent-based induction regimens on SC harvest, response and survival among patients with MM treated in the Department of Clinical Therapeutics of the University of Athens, Greece. From January 1996 to June 2009, 210 consecutive patients who underwent ASCT were classified according to the induction regimens to: those who had received conventional chemotherapy (CC) only (MP, CD or VAD) (group A); those who were treated with CC followed by novel agent-based regimens (dexamethasone plus an IMiD and/or bortezomib; group B); and patients who were treated with novel agent-based regimens only prior to SC collection (group C). Stem cells were mobilized with G-CSF alone or with cyclophosphamide and G-CSF. Group A included 102 (49%) patients, group B 72 (34%) and group C 33 (16%) patients. Induction with novel agents only (group C) yielded a significantly greater SC collection compared to induction with CC only (group A) or CC followed by novel agent-based therapies (group B) (p=0.006 and p=0.038, respectively). The mean number of collected CD34+ cells/kg was 10×106 (range 2-43.2×106), 10.4×106 (range 2-49×106) and 15.1×106 (range 2-65×106) for groups A, B and C, respectively. The probability to collect a number of at least 5×106 CD34+ cells/kg was significantly higher in patients who received novel agents only when compared to those of groups A and B (78.8% vs. 57.5%, p=0.021). Among patients of group A, those who received induction with VAD had a significantly greater SC collection when compared to MP or CD (mean CD34+ cells/kg collected: 12.2×106vs. 7.56×106 /kg; p=0.031). Moreover, SC yield did not differ between patients who received VAD only or novel agent-based regimens only, as induction therapy (p=0.155). Engraftment data were comparable between the three groups. Age >55 years (p=0.039) and prior radiation therapy (p<0.0001) negatively influenced SC collection. The administration of novel agent-based regimens alone was associated with superior response rate prior to ASCT compared to CC alone as induction therapy (objective response (OR) 87.5% vs. 61.7%, p=0.007; at least vgPR 27.2% vs. 18.9%, p=0.032, for groups C and A, respectively). However, post-ASCT, patients of groups A and C achieved similar response rates (OR: 94.6% vs. 92.9%, p=0.736 and at least vgPR: 53.6% vs. 46.7%, p=0.526). The median OS, from the date of ASCT, in all patients was 74 months. Factors associated with longer OS included the achievement of CR or sCR post-ASCT (p=0.027), ISS-1 and -2 vs. ISS-3 (p=0.007), low beta2-microglobulin (<3.5 mg/mL) prior to ASCT (p=0.023), low marrow infiltration by plasma cells (<5%) prior to ASCT (p=0.016) and normal MRI pattern at diagnosis (vs. focal and diffuse, p=0.027). The use of novel agent-based regimens in induction therapy was associated with a probability of 4-year OS of 88% compared to 54% in patients of group A. There was a trend in favor of novel agent-based regimens as induction therapy in terms of OS (median 89 vs. 62 months, for patients of groups B+C and A, respectively; p=0.144). Furthermore, patients of group C had superior EFS post-ASCT compared to patients of group A (median 84 vs. 27 months; p=0.046). Other variables like mobilization regimen before HDT (cyclo 4g/m2+G-CSF vs. cyclo 2.5 g/m2+G-CSF vs. G-CSF only), high dose therapy dosage (melphalan 200 mg/m2vs. 180 mg/m2vs. 140mg/m2 or less), and the interval from diagnosis to ASCT (more or less than one year) did not correlate with OS or PFS. In conclusion, our study demonstrates that patients who received induction therapy with novel agents only prior to ASCT had a higher number of CD34+ cells collected when compared to induction with CC followed by novel agent-based regimens or CC alone. Furthermore, these patients achieved a higher response rate and a better quality of response before HDT, compared to patients who received CC only, but this did not correspond to a higher response rate post-ASCT. Further follow-up is needed to fully assess the impact of novel agent induction on patient's OS. Disclosures: No relevant conflicts of interest to declare.

A Six Year Prospective Study of Fibrinogen and Other Risk Factors Associated with Mortality in Stable Claudicants

1992 ◽  
Vol 68 (03) ◽  
pp. 261-263 ◽  
Author(s):  
A K Banerjee ◽  
J Pearson ◽  
E L Gilliland ◽  
D Goss ◽  
J D Lewis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Intermittent Claudication ◽  
Fibrinogen Level ◽  
Past History ◽  
Fold Increase ◽  
Arterial Disease ◽  
Plasma Fibrinogen ◽  
Plasma Fibrinogen Level ◽  
Factors Associated ◽  
Probability Of Death

SummaryA total of 333 patients with stable intermittent claudication at recruitment were followed up for 6 years to determine risk factors associated with subsequent mortality. Cardiovascular diseases were the underlying cause of death in 78% of the 114 patients who died. The strongest independent predictor of death during the follow-up period was the plasma fibrinogen level, an increase of 1 g/l being associated with a nearly two-fold increase in the probability of death within the next 6 years. Age, low ankle/brachial pressure index and a past history of myocardial infarction also increased the probability of death during the study period. The plasma fibrinogen level is a valuable index of those patients with stable intermittent claudication at high risk of early mortality. The results also provide further evidence for the involvement of fibrinogen in the pathogenesis of arterial disease.

Sign in / Sign up

Export Citation Format

Share Document