scholarly journals Patterns of Care and Outcomes Among Older Patients with Myelofibrosis: A Population-Based Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Shelby Meckstroth ◽  
Rong Wang ◽  
Xiaomei Ma ◽  
Nikolai A. Podoltsev
Keyword(s):  
Median Survival ◽  
Research Funding ◽  
Multivariable Analysis ◽  
Population Based ◽  
Janus Kinase ◽  
Patterns Of Care ◽  
Age At Diagnosis ◽  
Jak Inhibitor ◽  
Risk Of Death

Background: Myelofibrosis (MF) is a Philadelphia chromosome negative myeloproliferative neoplasm associated with systemic and splenomegaly-related symptoms, cytopenias and decreased survival. Approval of ruxolitinib, an oral janus kinase (JAK)-inhibitor, for higher-risk MF patients (pts) by the Food and Drug Administration in 11/ 2011 opened a new era of targeted treatment for this disease. There are limited data on the "real-world" clinical experiences and outcomes of pts with MF treated in the JAK inhibitor era. MF became reportable to population-based cancer registries including the Surveillance, Epidemiology and End Results (SEER) program in 2001, making its investigation possible at the population level. The objective of this study was to assess the patterns of care and outcomes of older MF pts in the ruxolitinib era. Methods: Using the linked SEER-Medicare database, we identified a cohort of older pts diagnosed with MF from 2007 through 2015 who fulfilled the following eligibility criteria: 1) aged 66-99 years at diagnosis; 2) had known month of diagnosis; 3) were not identified from death certificate or autopsy only; 4) had continuous enrollment in Medicare Parts A, B and no enrollment in health maintenance organizations from 1 year before diagnosis until the end of follow-up (death or 12/31/2016, whichever came first); 5) had continuous enrollment in Medicare Part D from diagnosis until the end of follow-up; and 6) bone marrow biopsy claim from 1 year before diagnosis to end of follow up. Treatments were assessed via Medicare parts B&D claims. Kaplan-Meier curves and log-rank tests were used to compare survival between patient groups. Multivariable cox proportional hazards regression models were used to assess the effect of ruxolitinib use on survival in MF pts. Aside from treatment, we considered the influence of several characteristics on survival, including age at diagnosis, sex, race/ethnicity, marital status, comorbidities, SEER region and percentage living in poverty at the census tract level. Results: Among 528 MF pts, median age at diagnosis was 76 (interquartile range [IQR], 71- 80) years with 88.8% white and 56.1% male. 230 pts were diagnosed in the early era (2007-2011), and 298 in the late era (2012-2015), of which 113 (37.9%) were ruxolitinib users. There was no difference among any evaluated characteristics between two eras and by ruxolitinib status in the late era. The median duration of ruxolitinib use was 11.9 months. Similar number of pts started at 5, 10, 15 and 20 mg twice a day (BID) (Figure 1). Among 31 pts who started at ≤5 mg BID, 15 (48.4%) never had their dose of ruxolitinib escalated. While on ruxolitinib treatment, nearly half of the pts received additional medications for symptom management including hydroxyurea (22.6%), prednisone (17.9%) or both (10.4%). < 11 users were able to go up to the highest dose of 25 mg BID. Ruxolitinib was interrupted > 30 days for 31 times by 20 of 113 (17.7%) pts with median interruption duration of 43 (IQR 34-71) days. The median survival was 2.70 (95% confidence interval [CI]: 1.87-3.41) years and 2.62 (95% CI: 2.15-3.07) for the early and late era pts, respectively (p for log-rank 0.91). The multivariable analysis showed no impact of diagnosis era on survival (late vs early era hazard ratio (HR) of 1.08, 95% CI 0.83-1.40; p= 0.57). There was no difference in survival by ruxolitinib status (log-rank test, p=0.31), with a median survival of 2.76 (95% CI: 2.01-4.15) years and 2.53 (95% CI: 1.92-3.07) years among users and non-users, respectively (Figure 3). In the multivariable analysis, the risk of death among ruxolitinib users compared to non-users was not statistically significant with HR of 0.82 (95% CI 0. 59-1.16; p= 0.26). Conclusions: Older MF pts treated with ruxolitinib had similar survival when compared to pts who did not receive this medication, but the choice of ruxolitinib might have been influenced by disease risk which we were unable to assess. For many ruxolitinib users, the drug was interrupted, the dose was not escalated, additional medications were used concurrently (possibly to help control disease manifestation), and treatment was discontinued quickly after initiation. Optimization of ruxolitinib use may be necessary to accomplish better outcomes. Furthermore, development of new drugs which may be used together with ruxolitinib or after its discontinuation is needed. The work was supported by The Frederick A. Deluca Foundation. Disclosures Wang: Celgene/BMS: Research Funding. Ma:Celgene/BMS: Research Funding; BMS: Consultancy. Podoltsev:Jazz Pharmaceuticals: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Agios Pharmaceuticals: Consultancy, Honoraria; Sunesis Pharmaceuticals: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Blueprint Medicines: Consultancy, Honoraria; Bristol-Myers Squib: Consultancy, Honoraria; Genentech: Research Funding; AI Therapeutics: Research Funding; Samus Therapeutics: Research Funding; Astellas Pharma: Research Funding; Kartos Therapeutics: Research Funding; CTI biopharma: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Research Funding; Novartis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Astex Pharmaceuticals: Research Funding; Daiichi Sankyo: Research Funding; Arog Pharmaceuticals: Research Funding.

Changing The Treatment Paradigm For Previously Treated Chronic Lymphocytic Leukemia Patients With Del(17p) Karyotype

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2872-2872
Author(s):  
Deborah M Stephens ◽  
Amy Stark ◽  
Jeffrey A. Jones ◽  
Jennifer A. Woyach ◽  
Kami Maddocks ◽  
...  
Keyword(s):  
Treatment Group ◽  
Partial Response ◽  
Clinical Outcomes ◽  
Research Funding ◽  
Multivariable Analysis ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Molecular Characteristics ◽  
Risk Of Death

Abstract CLL patients (pts) with del(17p13.1) (17p-) karyotype typically have poor response to therapy and dismal clinical outcomes. We describe the success of treatment of 17p- pts on clinical trials at Ohio State University (OSU) with regimens based on 1 of 2 novel agents [ibrutinib (IB; an oral inhibitor of Bruton tyrosine kinase) or one of the cyclin-dependent kinase inhibitors (CDKi; alvocidib, dinaciclib, or TG02)]. We retrospectively reviewed records of 174 CLL pts with 17p- who received therapy prior to 1st treatment at OSU (OSU Tx1) from 2002-2013. Progression free survival (PFS) was calculated from date of OSU Tx1 until progression/death, censoring pts at date of second treatment prior to progression or last contact if alive and progression free. Overall survival (OS) was calculated from date of OSU Tx1 until date of death. Pts who received transplant or later IB were censored at that time; otherwise pts were censored at last follow-up or 48 mos if still alive. PFS/OS estimates were calculated using the Kaplan-Meier method. Proportional hazard models were fit with treatment group and adjusted for other prognostic variables (p<0.05). Median time from CLL diagnosis to OSU Tx1 was 5.6 yrs and median number of prior therapies was 3 (range: 1-10). At OSU Tx1, median age was 63 yrs (39-83), 66% were male, and 93% were Caucasian. ECOG performance status (PS) was 0, 1, and 2/3 in 28%, 60%, and 11% of pts, respectively, and 71% had Rai Stage 3/4. In addition to 17p-, 21%, 57%, and 16% of pts harbored 11q-, 13q- and tri(12) aberrations, while 70% had complex karyotype (CK; ≥3 abnormalities including 17p-). At OSU Tx1, 16% (n=27), 33% (n=58), and 51% (n=89) of pts received an IB-based therapy, CDKi-based therapy, or other therapies (O), respectively. Clinical and molecular characteristics were not statistically different across groups except the IB and CDKi groups had more pts with ≥3 prior therapies (70% in IB vs 64% in CDKi vs 42% in O, p=0.005) and the median white blood cell count (WBC) was lowest in the CDKi group [18.8 in IB vs 25.5 in O vs 12.1 in CDKi, p=0.04]. The degree of response to OSU Tx1 was significantly different among groups (p=0.007), where 56%, 45%, and 24% of pts in the IB, CDKi, and O groups, respectively, achieved at least a partial response, and 85%, 64%, and 53% achieved at least stable disease. As shown in Figure 1A, PFS was significantly extended with IB and CDKi compared to O (p<0.0001), and PFS was longer with IB compared to CDKi (p=0.002); 12 mos estimates were 77% (95%CI=0.56-0.89), 38% (95%CI=0.25-0.52), and 17% (95%CI=0.10-0.26) in the IB, CDKi, and O groups, respectively. As shown in Figure 1B, OS was significantly different among the IB, CDKi, and O groups (p=0.02), with 12 mos estimates of 81% (95%CI=0.61-0.92), 78% (95%CI=0.64-0.87), and 58% (95%CI=0.46-0.68). OS was extended with IB and CDKi compared to O (p=0.01 and p=0.04, respectively), although by 48 mos, estimates for CDKi and O were similar. With a median follow-up of 12 mos, no large differences between IB and CDKi were yet observed (p=0.49). In multivariable analysis, treatment group was significantly associated with achieving at least partial response (p=0.0005) independent of number of prior therapies and presence of 13q-. The odds of response were higher with IB and CDKi compared to O, but not significantly different between IB and CDKi (all pairwise odds ratios (OR): IB vs O=5.66 (95%CI=2.12-15.08); CDKi vs O=3.38 (95%CI=1.57-7.31); IB vs CDKi = 1.67 (95%CI=0.65-4.32)]. Treatment group was significantly associated with PFS (p<0.0001) independent of number of prior therapies, albumin, and CK. The risk of progression/death decreased by 90% and 60%, respectively, with IB or CDKi compared to O (all pairwise hazard ratios (HR): IB vs O=0.10 (95%CI=0.04-0.22); CDKi vs O=0.40 (95%CI=0.27-0.60); IB vs CDKi = 0.24 (95%CI=0.11-0.55)]. Treatment group was significantly associated with OS (p=0.003) independent of number of prior therapies, albumin, CK, ECOG PS, and WBC. The risk of death decreased by 73% and 47%, respectively with IB and CDKi compared to O (all pairwise HR: IB vs O=0.27 (95%CI=0.11-0.66); CDKi vs O=0.53 (95%CI=0.31-0.89); IB vs CDKi=0.52 (95%CI=0.21-1.30)]. Notably, age did not correlate with response, PFS, or OS. Treatment of 17p CLL pts with IB and CDKi at OSU have demonstrated improved response, PFS, and OS. These novel therapies provide hope for patients with a karyotype historically associated with dismal clinical outcomes. Disclosures: Jones: Pharmacyclics: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Byrd:Celgene: Consultancy; Johnson and Johnson: Consultancy; Pharmacyclics: Research Funding.

scholarly journals POS0119 RENAL INVOLVEMENT AND NEED OF RENAL REPLACEMENT THERAPY IN ANCA ASSOCIATED VASCULITIS IN A SPANISH SINGLE-CENTER STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 270.2-271
Author(s):  
J. Álvarez Troncoso ◽  
J. C. Santacruz Mancheno ◽  
A. Díez Vidal ◽  
S. Afonso Ramos ◽  
A. Noblejas Mozo ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Granulomatosis With Polyangiitis ◽  
Renal Involvement ◽  
Age At Diagnosis ◽  
Systemic Involvement ◽  
Risk Of Death ◽  
Anca Associated Vasculitis ◽  
The Mean

Background:Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EPGA). Renal involvement is frequent in AAV and is an important factor for morbidity and mortality.Objectives:The main objective of this study was to analyze the demographic, clinical, histological and therapeutic characteristics of renal involvement in patients with AAV and the risk of renal replacement therapy (RRT) or death.Methods:Retrospective observational study of 56 patients with AAV fulfilling classificatory criteria and renal involvement diagnosed between 1995 and 2020 from a Spanish tertiary centre. We studied the histological involvement (according to the 2010 classification in focal, crescentic, mixed or sclerotic), immunofluorescence (IF) and the treatment received with the risk of RRT or death.Results:We included 56 patients diagnosed with AAV and renal involvement. The mean age was 61.08±4.05 years; 58.9% were women. The mean follow-up time of these patients was 16.14± 8.80 years. Only 57.1% of patients presented systemic involvement.Most frequent non-renal AAV manifestations were lung involvement (39.3%), central nervous system (30.4%), otorhinolaryngology (ORL) (14.3%), skin (8.9%) and cardiac involvement (8.9%). Main immunological findings were ANCA-MPO+ (69.6%), ANCA-PR3+ (23.2%), ANCA-negative (5.4%). Low C3 was found in 19.6% patients. Histologic classification (HC) and need of RRT is described in table 1. Main HC in renal AAV was crescentic, mixed, focal and sclerotic respectively. Eight patients had not biopsy performed. IF was positive for C3 deposits in 20 patients (35.7%). Half of the patients presented <50% normal glomeruli.The treatment of renal involvement in AAV in our cohort was as follows: 83.9% (47) corticosteroids (CS) and cyclophosphamide (of which 40 received intravenous and 7 oral cyclophosphamide; and 12 patients associated plasma exchange (PE) with this treatment), 5.36% CS alone, 2 patients received CS and mycophenolate; 1 CS and rituximab, 1 CS and PE, and 2 patients received no treatment. A total of 13 patients received PE and 18 RRT. The mean time to RRT was 65.44±32.72 months. Relapses were not uncommon, 33.93% of the patients presented ≥1 relapse and 10.71% presented ≥2.Infections were very frequent since they were present in 91.07% of the patients. Other frequent non-immunological complications observed in the follow-up of these patients were thrombosis in 31.14%, cardiovascular events in 28.57% and cancer in 19.64%.Patients with ANCA-PR3+ were younger at diagnosis (p<0.001), were more likely to present cardiac (p=0.045) and ORL involvement (p<0.001). However, neither ANCA-PR3+ nor ANCA-MPO+ were specifically associated with the need of RRT or higher risk of death in our cohort. Use of CS alone for the treatment of renal AAV was associated with higher mortality (p=0.006) but CS and cyclophosphamide with lower mortality (p=0.044). ANCA-negative patients were more likely to receive no treatment. Having <50% normal glomeruli and C3 deposits on IF were associated with an increased need for RRT. Presenting focal disease on HC was protective for the need of RRT. Older age at diagnosis, systemic involvement of AAV and need of RRT was associated with higher mortality.Conclusion:AAVs are complex vasculitides with frequent renal involvement. Increased C3 deposition, non-focal histological forms, and <50% normal glomeruli were related to the need for RRT. In turn, the need for RRT, a later age at diagnosis, and systemic involvement were associated with higher mortality. Holistic and multidisciplinary early management of AAVs in experience centers can help improve renal prognosis and decrease mortality.References:[1]Binda et al. ANCA-associated vasculitis with renal involvement. J Nephrol. 2018 Apr;31(2):197-208.[2]Kronbichler et al. Clinical associations of renal involvement in ANCA-associated vasculitis. Autoimmun Rev. 2020 Apr;19(4):102495.Disclosure of Interests:None declared

scholarly journals Long-term mortality and active TB disease among patients who were lost to follow-up during second line tuberculosis treatment in 2011-2014: population-based study in the country of Georgia

2021 ◽  
Author(s):  
Giorgi Kuchukhidze ◽  
Davit Baliashvili ◽  
Natalia Adamashvili ◽  
Ana Kasradze ◽  
Russell R Kempker ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Positive Culture ◽  
Population Based ◽  
Drug Resistant ◽  
Second Line ◽  
Adjusted Risk ◽  
Tb Treatment ◽  
Country Of Georgia

Abstract BACKGROUND High rates of loss to follow-up (LFU) exist among patients with multi-drug and extensively drug-resistant tuberculosis (M/XDR TB); We aimed to identify long-term clinical outcomes of patients who were LFU during second-line TB treatment. METHODS We conducted a follow-up study among adults who received second-line TB treatment in the country of Georgia during 2011-2014 with a final outcome of LFU. We attempted to interview all LFU patients, administered a structured questionnaire and obtained sputum samples. Active TB at follow-up was defined by positive sputum Xpert-TB/RIF or culture. RESULTS Follow-up information was obtained for 461 patients, among these patients, 107 (23%) died and 177 (38%) were contacted, of those contacted 123 (69%) consented to participate and 92 provided sputum samples. Thirteen (14%) had active TB with an estimated infectious time-period for transmitting drug-resistant TB in the community of 480 days (IQR=803). In multivariable analysis, positive culture at the time of LFU was associated with active TB at the time of our study (adjusted risk ratio=13.3, 95% CI: 4.2, 42.2) CONCLUSIONS Nearly one-quarter of patients on second-line TB treatment who were LFU died. Among those LFU evaluated in our study, one in seven remained in the community with positive sputum cultures. To reduce death and transmission of disease, additional strategies are needed to encourage patients to complete treatment.

scholarly journals Cardiac Morbidity in Adolescents and Young Adult Survivors of Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Kristin C. Marr ◽  
Jonathan Simkin ◽  
Andrea C. Lo ◽  
Joseph M. Connors ◽  
Alina S. Gerrie ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Research Funding ◽  
Index Date ◽  
Population Based ◽  
Stage Disease ◽  
Increased Risk ◽  
Matched Case ◽  
Cv Disease ◽  
Relapsed Disease

INTRODUCTION Adolescents and young adult (AYA) survivors of Hodgkin lymphoma (HL) are potentially at increased risk of cardiovascular (CV) disease due to anthracycline exposure, in addition to use of mediastinal radiotherapy (RT). Although the risk has been well described in the pediatric age-group, the impact in the AYA population has been less well characterized. Capturing the incidence of these late effects is challenging given that events can occur more than a decade after therapy completion. Using population-based administrative data, we evaluated the incidence of CV disease (combined heart failure (HF) and ischemic heart disease (IHD)) in a cohort of AYA survivors treated for classical HL (cHL) using ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or equivalent chemotherapy. METHODS Patients with cHL aged 16-39 years (y), diagnosed between 1992-2013 and treated with an ABVD or equivalent therapy, were identified in the BC Cancer Lymphoid Cancer Database. Patients must have survived to an Index Date defined as 2 y from most recent HL event (primary diagnosis or if applicable, most recent relapse) and have had a minimum follow-up of 1 y beyond their Index Date. Patients were excluded if they had history of prior malignancy or HIV positivity. Limited stage disease was defined as stage IA, IB or IIA and absence of bulky disease (≥10cm); all others had advanced stage disease. Cases were linked with population-based databases of BC Cancer Registry; BC Radiation Oncology Database; and BC Ministry of Health (MOH) Chronic Disease Registry (CDR) that captures all BC residents registered with medical service plan coverage during the study period. The outcome variables, including HF and IHD, were defined by the BC MOH CDR using Standardized Case Definitions. To focus on late onset CV complications, only events that occurred after the Index Date were included in the analysis. A 10:1 individually-matched control population was identified from the CDR based on age, sex, and health authority region on the Index Date of the matched case. Controls were excluded if they had a pre-existing malignancy, HF, or IHD prior to the study window. Individual outcomes were collected from the Index Date of the matched case until December 31, 2015 or until an individual was censored due to loss to follow-up or death. Kaplan Meier (K-M) methodology and log-rank test was used to estimate cumulative incidence. A competing risk regression analysis was used to evaluate relative risk (RR) and p-values less than 0.05 were considered significant. RESULTS With a median follow-up time of 11 y (range 3-24 y) from most recent HL event, 764 AYA 2-y survivors were identified, aged 20 to 61 y (median 38 y) at the end of study period. The proportion of limited and advanced stage disease was 34.2% and 65.6%, respectively; and 49.9% were male. Eighty-eight patients (11.5%) had relapsed disease; eighty-six (11.3%) underwent high dose chemotherapy and autologous stem cell transplantation as part of their salvage therapy. In total, 268 patients (36.4%) were treated with mediastinal RT for primary therapy or for relapsed disease. Fifty-three percent received cumulative anthracycline dose ≥300 mg/m2. Survivors had a 3-fold increased risk of CV disease relative to controls (p&lt;0.0001). The onset of CV disease in survivors occurred at median of 11.7 y after most recent treatment (range 2.2-19.2 y), and at a median age of 44.3 y (range 21 - 58 y). At 15 y, the estimated cumulative incidence of CV disease was 6.3% in survivors compared to 2.3% in controls (Figure A). In the 496 survivors that received chemotherapy only, the incidence of CV disease at 15 y was 4.6% vs 2.3% in controls, and those that received anthracyclines and mediastinal RT had significantly higher incidence at 8.6% (Figure B). The increase in risk was greatest for a diagnosis of HF (RR 6.92, p&lt;0.0001): at 15 y, the cumulative incidence of HF was 2.2% vs 0.6% in controls. The RR of IHD was 2.63 (p&lt;0.0001) with incidence of 5.1% in cases compared to 1.8% in controls. CONCLUSION Similar to the pediatric population, AYA cHL survivors are at increased risk of both HF and IHD after completion of treatment. The majority of patients had received ABVD alone and had a lower incidence of CV disease at 15 y when compared to those that received treatment that included mediastinal RT. These results will inform counseling regarding risk factor modification and aid in the development of surveillance guidelines for AYA survivors. Disclosures Gerrie: Sandoz: Consultancy; Roche: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Astrazeneca: Consultancy, Research Funding. Villa:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; AZ: Consultancy, Honoraria, Research Funding; Kite/Gilead: Consultancy, Honoraria; Nano String: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Sandoz Canada: Consultancy, Honoraria; Immunovaccine: Consultancy, Honoraria; Purdue Pharma: Consultancy, Honoraria. Scott:NIH: Consultancy, Other: Co-inventor on a patent related to the MCL35 assay filed at the National Institutes of Health, United States of America.; Roche/Genentech: Research Funding; Celgene: Consultancy; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoString, Research Funding; Abbvie: Consultancy; AstraZeneca: Consultancy; Janssen: Consultancy, Research Funding. Sehn:AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; Verastem Oncology: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; Chugai: Consultancy, Honoraria. Savage:BeiGene: Other: Steering Committee; Roche (institutional): Research Funding; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie, Servier: Consultancy; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie: Honoraria.

scholarly journals Beta-Blockers Improved Survival Outcomes in Patients with Multiple Myeloma: A Retrospective Evaluation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3306-3306
Author(s):  
Yi L. Hwa ◽  
Qian Shi ◽  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Morie A. Gertz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Mayo Clinic ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Beta Blockers ◽  
Multivariable Analysis ◽  
Advisory Committees ◽  
Risk Of Death ◽  
Cardiac Medication

Abstract Introduction: A recent study revealed an antiproliferative and apoptotic effect of propranolol on multiple myeloma (MM) cells. Our previous small matched case-control study showed longer survival in patients with propranolol and other beta-blockers (BB) intake than those without. This larger scale study was conducted to confirm the positive association of BB and MM survival. Methods: We identified 1971 newly diagnosed pts seen at Mayo Clinic between 1995 and 2010. Cardiac medication usage after diagnosis of MM was extracted from patient records and categorized based on BB intake. Cause of death was collected with death due to MM as the primary interest event and death due to cardiac disease or other reasons as competing risk events. The primary outcomes were MM disease-specific survival (DSS) and overall survival (OS). Cumulative incidence functions and Kaplan-Meier method were used to estimate the 5-year cumulative incidence rate (CIR) of MM death and OS rate, respectively. DSS and OS were compared by Gray's test and log-rank test, respectively. Multivarable Cox proportional hazard models were used to estimate the adjusted cause-specific HR (HRCSadj.) and hazard ratio (HRadj.) for DSS and OS, respectively, adjusting for demographics, disease characteristics, diagnosis year, and various chemotherapies. Results: 930 (47.2%) of MM patients had no intake of any cardiac medications; 260 (13.2%) had BB only; 343 (17.4%) used both BB / non-BB cardiac medications; and 438 patients (22.2%) had non-BB cardiac drugs. Five-year CIR of MM death and OS rate were shown in table. Superior MM DSS was observed for BB only users, compared to patients without any cardiac drugs (HRCSadj., .53, 95% confidence interval [CI], .42-.67, padj.<.0001) and non-BB cardiac drugs users (HRCSadj., .49, 95% CI, .38-.63, padj.<.0001). Patients received both BB and other cardiac drugs also showed superior MM DSS than non-cardiac drugs users (HRCSadj.., .54, 95% CI, .44-.67, padj.<.0001) and non-BB cardiac drug users. (HRCSadj., .50, 95% CI, .40-.62, padj.<.0001). MM DSS does not differ between BB users with and without other cardiac drugs (padj.=0.90). Multivariable analysis showed the same pattern for OS. None of the MM therapies impacted the differences in DSS and OS among BB intake groups (interaction padj.>.60). Conclusion: MM patients with BB intake showed reduced risk of death due to MM and overall mortality compared to patients who used non-BB cardiac or never used cardiac drugs. The result warrants further investigation for anti-cancer effect of BB in MM. Disclosures Shi: Mayo Clinic: Employment. Kumar:Onyx: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Glycomimetics: Consultancy; Janssen: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; BMS: Consultancy; Kesios: Consultancy. Gertz:NCI Frederick: Honoraria; Celgene: Honoraria; Med Learning Group: Honoraria, Speakers Bureau; Research to Practice: Honoraria, Speakers Bureau; Alnylam Pharmaceuticals: Research Funding; Novartis: Research Funding; Prothena Therapeutics: Research Funding; Ionis: Research Funding; Annexon Biosciences: Research Funding; GSK: Honoraria; Sandoz Inc: Honoraria. Kapoor:Celgene: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Dispenzieri:pfizer: Research Funding; Celgene: Research Funding; Alnylam: Research Funding; Jannsen: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Prothena: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals The Impact of Clonal Hematopoiesis of Indeterminate Potential on Survival in Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4359-4359
Author(s):  
Koji Sasaki ◽  
Rashmi Kanagal-Shamanna ◽  
Guillermo Montalban-Bravo ◽  
Rita Assi ◽  
Kiran Naqvi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Next Generation ◽  
Risk Of Death ◽  
Genetics Research ◽  
The Impact ◽  
Generation Sequencing

Abstract Introduction: Clearance of detected somatic mutations at complete response by next-generation sequencing is a prognostic marker for survival in patients with acute myeloid leukemia (AML). However, the impact of allelic burden and persistence of clonal hematopoiesis of indeterminate potential (CHIP)-associated mutations on survival remains unclear. The aim of this study is to evaluate the prognostic impact of allelic burden of CHIP mutations at diagnosis, and their persistence within 6 months of therapy. Methods: From February 1, 2012 to May 26, 2016, we reviewed 562 patients with newly diagnosed AML. Next-generation sequencing was performed on the bone marrow samples to detect the presence of CHIP-associated mutations defined as DNMT3A, TET2, ASXL1, JAK2 and TP53. Overall survival (OS) was defined as time period from the diagnosis of AML to the date of last follow-up or death. Univariate (UVA) and multivariate Cox proportional hazard regression (MVA) were performed to identify prognostic factors for OS with p value cutoff of 0.020 for the selection of variables for MVA. Landmark analysis at 6 months was performed for the evaluation of the impact of clearance of CHIP, FLT3-ITD, FLT3D835, and NPM1 mutations. Results: We identified 378 patients (74%) with AML with CHIP mutations; 134 patients (26%) with AML without CHIP mutations. The overall median follow-up of 23 months (range, 0.1-49.0). The median age at diagnosis was 70 years (range, 17-92) and 66 years (range, 20-87) in CHIP AML and non-CHIP AML, respectively (p =0.001). Of 371 patients and 127 patients evaluable for cytogenetic in CHIP AML and non-CHIP AML, 124 (33%) and 25 patients (20%) had complex karyotype, respectively (p= 0.004). Of 378 patients with CHIP AML, 183 patients (48%) had TET2 mutations; 113 (30%), TP53; 110 (29%), ASXL1; 109 (29%), DNMT3A; JAK2, 46 (12%). Of 378 patients, single CHIP mutations was observed in 225 patients (60%); double, 33 (9%); triple, 28 (7%); quadruple, 1 (0%). Concurrent FLT3-ITD mutations was detected in 47 patients (13%) and 12 patients (9%) in CHIP AML and non-CHIP AML, respectively (p= 0.287); FLT3-D835, 22 (6%) and 8 (6%), respectively (p= 0.932); NPM1 mutations, 62 (17%) and 13 (10%), respectively (p= 0.057). Of 183 patients with TET2-mutated AML, the median TET2 variant allele frequency (VAF) was 42.9% (range, 2.26-95.32); of 113 with TP53-mutated AML, the median TP53 VAF, 45.9% (range, 1.15-93.74); of 109 with ASXL1-mutated AML, the median ASXL1 VAF was 34.5% (range, 1.17-58.62); of 109 with DNMT3A-mutated AML, the median DNMT3A VAF was 41.8% (range, 1.02-91.66); of 46 with JAK2-mutated AML, the median JAK2 VAF was 54.4% (range, 1.49-98.52). Overall, the median OS was 12 months and 11 months in CHIP AML and non-CHIP AML, respectively (p= 0.564); 16 months and 5 months in TET2-mutated AML and non-TET2-mutated AML, respectively (p <0.001); 4 months and 13 months in TP53-mutated and non-TP53-mutated AML, respectively (p< 0.001); 17 months and 11 months in DNMT3A-mutated and non-DNMT3A-mutated AML, respectively (p= 0.072); 16 months and 11 months in ASXL1-mutated AML and non-ASXL1-mutated AML, respectively (p= 0.067); 11 months and 12 months in JAK2-murated and non-JAK2-mutated AML, respectively (p= 0.123). The presence and number of CHIP mutations were not a prognostic factor for OS by univariate analysis (p=0.565; hazard ratio [HR], 0.929; 95% confidence interval [CI], 0.722-1.194: p= 0.408; hazard ratio, 1.058; 95% confidence interval, 0.926-1.208, respectively). MVA Cox regression identified age (p< 0.001; HR, 1.036; 95% CI, 1.024-1.048), TP53 VAF (p= 0.007; HR, 1.009; 95% CI, 1.002-1.016), NPM1 VAF (p=0.006; HR, 0.980; 95% CI, 0.967-0.994), and complex karyotype (p<0.001; HR, 1.869; 95% CI, 1.332-2.622) as independent prognostic factors for OS. Of 33 patients with CHIP AML who were evaluated for the clearance of VAF by next generation sequencing , landmark analysis at 6 months showed median OS of not reached and 20.3 months in patients with and without CHIP-mutation clearance, respectively (p=0.310). Conclusion: The VAF of TP53 and NPM1 mutations by next generation sequencing can further stratify patients with newly diagnosed AML. Approximately, each increment of TP53 and NPM1 VAF by 1% is independently associated with 1% higher risk of death, and 2% lower risk of death, respectively. The presence of CHIP mutations except TP53 does not affect outcome. Disclosures Sasaki: Otsuka Pharmaceutical: Honoraria. Short:Takeda Oncology: Consultancy. Ravandi:Macrogenix: Honoraria, Research Funding; Seattle Genetics: Research Funding; Sunesis: Honoraria; Xencor: Research Funding; Jazz: Honoraria; Seattle Genetics: Research Funding; Abbvie: Research Funding; Macrogenix: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Orsenix: Honoraria; Abbvie: Research Funding; Jazz: Honoraria; Xencor: Research Funding; Orsenix: Honoraria; Sunesis: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Astellas Pharmaceuticals: Consultancy, Honoraria. Kadia:BMS: Research Funding; Abbvie: Consultancy; Takeda: Consultancy; Jazz: Consultancy, Research Funding; Takeda: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Research Funding; Novartis: Consultancy; Amgen: Consultancy, Research Funding; BMS: Research Funding; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; Abbvie: Consultancy; Celgene: Research Funding. DiNardo:Karyopharm: Honoraria; Agios: Consultancy; Celgene: Honoraria; Medimmune: Honoraria; Bayer: Honoraria; Abbvie: Honoraria. Cortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Arog: Research Funding.

A population-based study of acute panmyelosis with myelofibrosis in the United States: 2004 to 2015.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19003-e19003
Author(s):  
Nicole McLaughlin ◽  
Gordon Ruan ◽  
Courtney N. Day ◽  
William S. Harmsen ◽  
Caleb J. Smith ◽  
...  
Keyword(s):  
United States ◽  
Multivariable Analysis ◽  
The United States ◽  
Population Based ◽  
Cox Proportional Hazards Model ◽  
Seer Database ◽  
Univariable Analysis ◽  
Adjusted Analysis ◽  
Male Sex

e19003 Background: Acute panmyelosis with myelofibrosis (APMF) is a rare subtype of acute myeloid leukemia characterized by acute panmyeloid proliferation with increased blasts, cytopenias with bone marrow fibrosis, and absence of splenomegaly. There is a paucity of population-based studies of APMF. Methods: We queried the United States Surveillance, Epidemiology, and End Results (SEER) database and National Cancer Database (NCDB) using the ICD-O-3 code 9931/3. The SEER 17 registries (2004-2015) were used to find data on incidence. For NCDB data, comorbid disease burden was calculated using the Charlson-Deyo Score (CDS). Hazard ratios (HR) with confidence intervals (CI) were calculated using a Cox proportional hazards model. Overall survival (OS) was estimated with the Kaplan-Meier method. Variables significant in univariable analysis were included in a multivariable analysis. Results: We identified 260 APMF patients using the SEER database. Incidence was 0.3 cases/million individuals and did not change significantly from 2004-2015. With a median follow up of 6.9 years (95% CI 6.1-7.8), the median OS was 2.3 years (95% CI 1.7-2.8). We identified 530 APMF patients using the NCDB. The median age at diagnosis was 67 years (range 22-90) and 311 (59%) were male. With a median follow up of 5.0 years (95% CI 3.0-7.6), the median OS was 2.3 years (95% CI: 0.8-6.5). OS was 69%, 31%, and 18% at 1-, 5-, and 10- years, respectively. Patients diagnosed in 2012-2015 had a significantly improved OS compared to those diagnosed in 2004-2007 (HR 0.65, 95% CI 0.49-0.85; p=0.002). 271 patients (53%) patients received chemotherapy. The OS for those that received chemotherapy was 70% at 1 year and 30% at 5 years versus 70% and 32% at 1- and 5- years for those who did not ( p=0.99). The median time to chemotherapy from time of diagnosis was 25 days (range 0-532 days). 52 patients (10%) underwent transplantation and the OS of those patients was 90% at 1 year and 45% at 5 years versus 67% and 29% at 1- and 5- years for those who did not (HR: 1.7 (95% CI: 1.2-2.6), p=0.006). In univariable analysis, factors predicting inferior OS were age ≥ 65 years old at diagnosis (HR 1.8, 95% CI 1.5-2.3; p<0.001), male sex (HR 1.5, 95% CI 1.2-1.8; p<0.001), CDS ≥ 1 (HR: 1.5 (95% CI: 1.2-2.0), p<0.001), government insurance (HR 1.8, 95% CI 1.4-2.3; p<0.001), diagnosis at a non-academic facility (HR 1.6, 95% CI 1.2-2.0, p<0.001), and not receiving a hematologic transplant (HR 1.7, 95% CI 1.2-2.6; p=0.006). Multivariable-adjusted analysis is shown in the Table. Conclusions: The overall incidence of APMF has not changed between 2004 and 2015, but OS for 2012-2015 was improved compared to 2004-2007. Age ≥ 65 years old, male sex, CDS ≥ 1, and diagnosis at a nonacademic facility predicted inferior OS. Multivariable-adjusted analysis.[Table: see text]

Prognostic value of weight loss in patients with amyotrophic lateral sclerosis: a population-based study

2020 ◽  
Vol 91 (8) ◽  
pp. 867-875 ◽  
Author(s):  
Mark R Janse van Mantgem ◽  
Ruben P A van Eijk ◽  
Hannelore K van der Burgh ◽  
Harold H G Tan ◽  
Henk-Jan Westeneng ◽  
...  
Keyword(s):  
Weight Loss ◽  
Amyotrophic Lateral Sclerosis ◽  
Body Weight ◽  
Prognostic Value ◽  
Population Based ◽  
Data Set ◽  
Population Based Study ◽  
Risk Of Death ◽  
Lateral Sclerosis

ObjectiveTo determine the prevalence and prognostic value of weight loss (WL) prior to diagnosis in patients with amyotrophic lateral sclerosis (ALS).MethodsWe enrolled patients diagnosed with ALS between 2010 and 2018 in a population-based setting. At diagnosis, detailed information was obtained regarding the patient’s disease characteristics, anthropological changes, ALS-related genotypes and cognitive functioning. Complete survival data were obtained. Cox proportional hazard models were used to assess the association between WL and the risk of death during follow-up.ResultsThe data set comprised 2420 patients of whom 67.5% reported WL at diagnosis. WL occurred in 71.8% of the bulbar-onset and in 64.2% of the spinal-onset patients; the mean loss of body weight was 6.9% (95% CI 6.8 to 6.9) and 5.5% (95% CI 5.5 to 5.6), respectively (p<0.001). WL occurred in 35.1% of the patients without any symptom of dysphagia. WL is a strong independent predictor of survival, with a dose response relationship between the amount of WL and the risk of death: the risk of death during follow-up increased by 23% for every 10% increase in WL relative to body weight (HR 1.23, 95% CI 1.13 to 1.51, p<0.001).ConclusionsThis population-based study shows that two-thirds of the patients with ALS have WL at diagnosis, which also occurs independent of dysphagia, and is related to survival. Our results suggest that WL is a multifactorial process that may differ from patient to patient. Gaining further insight in its underlying factors could prove essential for future therapeutic measures.

scholarly journals SURVIVAL ADVANTAGE OF APOE2

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S621-S621
Author(s):  
Sudha Seshadri
Keyword(s):  
Lower Risk ◽  
Large Population ◽  
Population Based ◽  
European Ancestry ◽  
Aggregated Data ◽  
Risk Of Death ◽  
Apoe Ε4 ◽  
Increased Risk ◽  
Ε4 Allele

Abstract Apolipoprotein E is a glycoprotein mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has been associated with higher risk of Alzheimer’s disease and of mortality, but the effect of the less prevalent APOE-ε2 on survival remains elusive. We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six large population-based cohorts to determine the association of APOE-ε2, with survival in the general population. During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P=1.1*10-2), whereas APOE-ε4 carriers were at increased risk (HR 1.17,1.12-1.21; P=2.8*10-16). Risk was lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). Results did not differ by sex. The association was unaltered after adjustment for baseline LDL or cardiovascular disease. Larger, multiethnic collaborations are ongoing.

Primary Extranodal Lymphoma: Revised Incidence, Location, Histological Classification and Survival in Zaragoza (Spain), 1992–2002

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4674-4674
Author(s):  
Pilar Giraldo ◽  
Esther Franco-Garcia ◽  
Ramiro Alvarez ◽  
Gloria Garcia-Carpintero ◽  
Mercedes Pascual ◽  
...  
Keyword(s):  
Median Survival ◽  
Relative Survival ◽  
Population Based ◽  
European Population ◽  
Extranodal Lymphoma ◽  
The European Union ◽  
Primary Location ◽  
Hodgkin's Lymphomas ◽  
Incident Cases

Abstract Background. Leukaemia and non-Hodgkin’s lymphomas (NHL) are the commonest haematological malignancies (HMs), accounting for about 10% of incident cases and 6% of all cancer deaths in the European Union (EU). There are few studies in order to estimate the differences in incidence and survival of primary extranodal Lymphoma (PEL). In Zaragoza (Spain) there is a population-based Cancer Registry (ZPCR), that includes all non-haematological and haematological (HMs) incident cases, conducted since 1960. The main aims of this study are: To review all cases with PEL diagnosis. To estimate the incidence of PEL in the ZPCR registered cases during the period 1992–2002. 2. To calculate the survival of PEL Methods. All PEL occurred in patients residing in Zaragoza during the period 1992–2002 were selected from ZPCR. All cases were reviewed in order to confirm the primary location and the morphology classification according to REAL. The population at risk was 9.266.609 person-years. The crude (CIR) and age standardized incidence rate (ASR) were calculated, using the European population as standard. Kaplan-Maier method was applied to calculate median survival time and their 95% confidence intervals, as well as 5-year survival. The end of follow-up was 31 December 2007 and Log-Rank was used to compare survival curves. Results. Among all 4,340 HMs, a total of 1,757 (40.0%) were NHL (CIR: 19×105 person-year), 252 (14.0%) of them were classified as PEL, yielding an ASR of 2.1×105 person-year (males: 140 cases (53.0%), mean age: 59.2 years, ASR: 2.7×105 person-year and females 112 cases (47.0%), mean age: 66.8 years ASR: 1.6×105 person-year. According to topography the most frequent sites were digestive tract (50.4%), skin (19.8%), gland tissue (10.0%), oral cavity-pharynx (7.9%), lung (2.9%), CNS (2.4%), orbit (2.1%) and others (4.5%). The median survival for PEL was 6.61 years (95%CI: 3.7–9.5) and for nodal Lymphomas 5.01 years (95%CI: 4.1–5.9). The 5-year relative survival was 53.5% and 50.0% respectively. There are not significant differences between both groups. Moreover, non significant differences in survival were observed between males and females. Theses results are similar to those found in the EU. Conclusions. The occurrence of PEL according to gender and mean age is similar to nodal NHL. No significant differences in survival were observed between nodal and extranodal NHL, probably the survival is more conditioned by the histology than topography.

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