scholarly journals Survival of Mantle Cell Lymphoma in the Era of Bruton Tyrosine Kinase Inhibitors: A Population-Based Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 182-182
Author(s):  
Mengyang Di ◽  
Can Cui ◽  
Shalin K. Kothari ◽  
Amer M. Zeidan ◽  
Nikolai Podoltsev ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Research Funding ◽  
Age Groups ◽  
Population Based ◽  
Sensitivity Analyses ◽  
Mantle Cell ◽  
All Cause Mortality ◽  
Bruton Tyrosine Kinase ◽  
Support Research

Abstract Background: Despite advances in chemoimmunotherapy and stem cell transplantation, mantle cell lymphoma (MCL) has historically been difficult to treat. Patients with advanced age and high-risk features (e.g. blastoid/pleomorphic features, high MIPI score, complex karyotype, TP53 mutation) face particularly poor outcomes with standard chemoimmunotherapy. Ibrutinib, a Bruton tyrosine kinase inhibitor (BTKi), was approved for second-line use in MCL in 2013. Other BTKis - acalabrutinib and zanubrutinib were approved in 2017 and 2019, respectively. BTKi provides a well-tolerated chemotherapy-free option for these hard-to-treat subgroups, especially the older patients. In this population-based study, we evaluated survival outcomes prior to and after the approval of ibrutinib, and hypothesized that survival benefit observed early after approval would be greatest in older patients not typically candidates for consolidative transplantation in the first-line setting. Methods: Using the Surveillance, Epidemiology, and End Results database, we included all adult patients diagnosed with MCL in the years 2007-2018 and followed them to the end of 2018 or death, whichever came first. The pre-BTKi era was defined by year of diagnosis 2007-2011, and the BTKi era was between 2014 and 2018. The years 2012-2013 were considered as a "washout" period to allow practice change related to the approval of ibrutinib. As age plays an important role in treatment decisions, including whether to use consolidative transplantation, patients were divided based on age at diagnosis: <60, 60-69, 70-79, and ≥80 years. Outcomes of interest included all-cause mortality, and mortality from MCL (MFM). We applied multivariable Cox proportional hazards regression model for all-cause mortality, adjusting for age, sex, race, stage, and median household income at census level, and reported adjusted hazard ratio (HR) with 95% confidence interval (CI). We also conducted multivariable competing risk analyses for MFM, considering all other causes of death as the competing events, and reported subhazard ratio (sHR) with 95% CI. To eliminate potential confounding by duration of follow-up among patients diagnosed in different periods, we used only three-year follow-up data for primary analyses, and all available follow-up data for sensitivity analyses. Results: We identified 7,625 individuals diagnosed with MCL during our study period (3,424 and 4,201 diagnosed during 2007-2011 and 2014-2018, respectively). The majority were male (71%) and white (90%), with 49% of patients 70 years or older. The median follow-up was 9.2 and 2.4 years for patients diagnosed during 2007-2011 and 2014-2018, respectively. The 3-year all-cause mortality and 3-year MFM rates were 39.8% and 27.3%, respectively, in the overall population. Both the 3-year all-cause mortality and MFM increased as age increased. The 3-year all-cause mortality was lower in the BTKi era among all age groups, except patients <60 years old, and the 3-year MFM was lower in the BTKi era among all age groups. The numeric difference of 3-year outcomes was more substantial in patients aged 70-79 for both all-cause mortality (pre-BTKi era: 47.8%, BTKi era: 40.4%) and MFM (pre-BTKi era: 33.9%, BTKi era: 27.5%) (Table, Figure A and B). In the multivariable analyses, risk of death was significantly lower during the BTKi era in the 60-69 (HR:0.85, 95% CI: 0.72-1.00) and 70-79 (HR: 0.80, 95% CI: 0.70-0.92) age groups. MFM was also significantly lower during the BTKi era in these two age groups (60-69: sHR: 0.78, 95% CI: 0.64-0.94; 70-79: sHR: 0.76, 95% CI: 0.65-0.90, Table). The results were largely unchanged in sensitivity analyses (results not shown). Conclusion: In this large population-based cohort analysis of individuals diagnosed with MCL, overall and lymphoma-specific survival improved in the BTKi era. At a median follow up of 2.4 years in our BTKi cohort, significant survival benefits were observed in those older than 60 but less than 80 years of age, and the observed benefits were greatest in the 70-79 age group. Future real-world studies should examine the impact of novel agents on treatment patterns and outcomes of MCL over a longer follow up period. Figure 1 Figure 1. Disclosures Kothari: Incyte pharmaceuticals: Consultancy, Honoraria; Karyopharm pharmaceuticals: Consultancy, Honoraria. Zeidan: Amgen: Consultancy, Research Funding; Astellas: Consultancy; Jasper: Consultancy; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; Boehringer Ingelheim: Consultancy, Research Funding; BeyondSpring: Consultancy; Acceleron: Consultancy, Research Funding; BioCryst: Other: Clinical Trial Committees; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding; Ionis: Consultancy; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; Astex: Research Funding; AstraZeneca: Consultancy; Epizyme: Consultancy; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy; Agios: Consultancy; ADC Therapeutics: Research Funding; Jazz: Consultancy; Genentech: Consultancy; Gilead: Consultancy, Other: Clinical Trial Committees; Incyte: Consultancy, Research Funding; Geron: Other: Clinical Trial Committees; Pfizer: Other: Travel support, Research Funding; Daiichi Sankyo: Consultancy; Kura: Consultancy, Other: Clinical Trial Committees; Aprea: Consultancy, Research Funding. Podoltsev: PharmaEssentia: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Bristol-Myers Squib: Honoraria; CTI BioPharma: Honoraria; Celgene: Honoraria; Blueprint Medicines: Honoraria; Pfizer: Honoraria. Neparidze: Janssen: Research Funding; Eidos Therapeutics: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Research Funding. Shallis: Curis: Divested equity in a private or publicly-traded company in the past 24 months. Ma: Celgene/Bristol Myers Squibb: Consultancy, Research Funding. Huntington: AbbVie: Consultancy; TG Therapeutics: Research Funding; SeaGen: Consultancy; DTRM Biopharm: Research Funding; Flatiron Health Inc.: Consultancy; Novartis: Consultancy; Bayer: Honoraria; Pharmacyclics: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Genentech: Consultancy; Servier: Consultancy; Thyme Inc: Consultancy; Celgene: Consultancy, Research Funding.

scholarly journals Real-World Outcomes for Pediatric and Young Adult Patients with Relapsed or Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (ALL) Treated with Tisagenlecleucel: Update from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 428-428
Author(s):  
Samuel John ◽  
Michael A. Pulsipher ◽  
Amy Moskop ◽  
Zhen-Huan Hu ◽  
Christine L. Phillips ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cell ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Ad Hoc ◽  
Age Groups ◽  
Advisory Committees ◽  
Advisory Boards

Abstract Background: Tisagenlecleucel is an autologous CD19-directed T-cell immunotherapy indicated in the USA for treatment of patients up to 25 years (y) of age with B-cell ALL that is refractory or in second or later relapse. Overall response rate was 82% with 24 months' (mo) follow-up in the registrational ELIANA trial [Grupp et al. Blood 2018]; pooled data from ELIANA and ENSIGN revealed similar outcomes upon stratification by age (<18y and ≥18y) [Rives et al. HemaSphere 2018]. Early real-world data for tisagenlecleucel from the CIBMTR registry reported similar efficacy to ELIANA with no new safety signals [Pasquini et al. Blood Adv 2020]. Outcomes are reported here for patients who received tisagenlecleucel in the real-world setting, stratified by age (<18y and ≥18y). Methods: This noninterventional prospective study used data from the CIBMTR registry and included patients aged ≤25y with R/R ALL. Eligible patients received commercial tisagenlecleucel after August 30, 2017, in the USA or Canada. Age-specific analyses were conducted in patients aged <18y and ≥18y at the time of infusion. Efficacy was assessed in patients with ≥12mo follow-up at each reporting center and included best overall response (BOR) of complete remission (CR), duration of response (DOR), event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS). Safety was evaluated in all patients who completed the first (100-day) assessment. Adverse events (AEs) of interest - including cytokine release syndrome (CRS) and neurotoxicity - were monitored throughout the reporting period. CRS and neurotoxicity were graded using the ASTCT criteria. Results: As of October 30, 2020, data from 451 patients were collected, all of whom received tisagenlecleucel. The median time from receipt of leukapheresis product at the manufacturing site to shipment was 27 days (interquartile range: 25-34). Patients aged ≥18y appeared to have greater disease burden at baseline than those aged <18y, indicated by lower rates of morphologic CR and minimal residual disease (MRD) negativity prior to infusion. Older patients were also more heavily pre-treated before infusion. All other patient characteristics at baseline were comparable between the two groups (Table 1). In the efficacy set (median follow-up 21.5mo; range 11.9-37.2; N=322), BOR of CR was 87.3% (95% CI 83.1-90.7); MRD status was available for 150 patients, of whom 98.7% were MRD negative. Median DOR was 23.9mo (95% CI 12.3-not estimable [NE]), median EFS was 14.0mo (9.8-24.8) and median RFS was 23.9mo (13.0-NE); 12mo EFS and RFS were 54.3% and 62.3%, respectively. For OS, the median was not reached. Efficacy outcomes were generally similar across age groups (Table 1). In the safety set (median follow-up 20.0mo; range 2.6-37.2; N=400), most AEs of interest occurred within 100 days of infusion. Any-grade CRS was observed in 58.0% of patients; Grade ≥3 in 17.8%. Treatment for CRS included tocilizumab (n=113; 28.3% of all patients) and corticosteroids (n=31; 7.8%). Neurotoxicity was observed in 27.3% of patients; Grade ≥3 in 10.0%. Treatment for neurotoxicity included tocilizumab (n=17; 4.3% of all patients) and corticosteroids (n=28; 7.0%). During the reporting period, 82 (20.5%) patients died; the most common cause of death was recurrence/persistence/progression of primary disease. CRS and chimeric antigen receptor (CAR)-T cell-related encephalopathy syndrome were the primary cause of death in 2 patients and 1 patient, respectively. Overall, safety data were similar across age groups, although more patients aged ≥18y experienced any-grade CRS or neurotoxicity and were subsequently treated (Table 1). Conclusions: Updated registry data for pediatric and young adult patients with R/R ALL treated with tisagenlecleucel revealed that patients aged ≥18y had a greater disease burden and were more heavily pre-treated at baseline than patients aged <18y. The overall efficacy and safety profiles of commercial tisagenlecleucel reflected those observed in the clinical trial setting [Grupp et al. Blood 2018; Rives et al. HemaSphere 2018] and were broadly consistent across age groups. Some important differences between the <18y and ≥18y groups were identified, which may point to challenges in timely identification and/or referral of older patients for CAR-T cell therapy. Figure 1 Figure 1. Disclosures Pulsipher: Equillium: Membership on an entity's Board of Directors or advisory committees; Adaptive: Research Funding; Jasper Therapeutics: Honoraria. Hu: Kite/Gilead: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Phillips: Novartis: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Margossian: Cue Biopharma, Inc.: Current Employment; Novartis: Other: Ad hoc Advisory Boards. Nikiforow: Kite/Gilead: Other: Ad hoc advisory boards; Novartis: Other: Ad hoc advisory boards; Iovance: Other: Ad hoc advisory boards; GlaxoSmithKline (GSK): Other: Ad hoc advisory boards. Martin: Novartis: Other: Local PI for clinical trial; Bluebird Bio: Other: Local PI for clinical trial. Rouce: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding; Pfizer: Consultancy. Tiwari: Novartis Healthcare private limited: Current Employment. Redondo: Novartis: Current Employment. Willert: Novartis: Current Employment. Agarwal: Novartis Pharmaceutical Corporation: Current Employment, Current holder of individual stocks in a privately-held company. Pasquini: Kite Pharma: Research Funding; GlaxoSmithKline: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Grupp: Novartis, Roche, GSK, Humanigen, CBMG, Eureka, and Janssen/JnJ: Consultancy; Novartis, Kite, Vertex, and Servier: Research Funding; Novartis, Adaptimmune, TCR2, Cellectis, Juno, Vertex, Allogene and Cabaletta: Other: Study steering committees or scientific advisory boards; Jazz Pharmaceuticals: Consultancy, Other: Steering committee, Research Funding.

scholarly journals Endometriosis and New-Onset Coronary Artery Disease in Taiwan: A Nationwide Population-Based Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Chun-Hui Wei ◽  
Renin Chang ◽  
Yu Hsun Wan ◽  
Yao-Min Hung ◽  
James Cheng-Chung Wei
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Age Groups ◽  
Population Based ◽  
Sensitivity Analyses ◽  
Increased Risk ◽  
Artery Disease ◽  
Stratified Analysis ◽  
New Onset

Endometriosis (EM) with chronic inflammation may accelerate the progression of atherosclerosis. Currently, no large or randomized clinical studies have assessed the incidence of cardiovascular events in patients with endometriosis in Asia to investigate whether incident EM is associated with a higher risk of new-onset coronary artery disease (CAD). In this study of a nationwide cohort in Taiwan, we identified 13,988 patients with newly diagnosed EM from 1 January, 2000, through 31 December, 2012. EM and non-EM groups were matched by propensity score at a ratio of 1:1. Of a total 27,976 participants, 358 developed CAD. The incidence rate in the EM group was higher than that in the non-EM group (1.8 per 1,000 person-years vs. 1.3 per 1,000 person-years) during the follow-up period. The adjusted hazard ratio (aHR) of CAD for the EM group was 1.52 with a 95% confidence interval (1.23–1.87, p < 0.001) after adjusting for demographic characteristics, comorbidities, surgical procedures, frequency of outpatient visits, and medications. Stratified analysis revealed that, among four age groups (20–39, 40–49, 50–54, and above 55 years), the 20–39 years sub-group was associated with a higher risk of CAD (aHR, 1.73; 95% CI, 1.16–2.59, p = 0.008). Several sensitivity analyses were conducted for cross-validation, and it showed consistent positive findings. In conclusion, this cohort study revealed that patients with symptomatic EM in Taiwan were associated with increased risk of subsequent CAD than patients without medical records of EM. Further prospective studies are needed to confirm this causal relationship.

scholarly journals Pre-Transplant Monocytic Myeloid-Derived Suppressor Cell Frequency Has No Prognostic Role for Outcome after Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in Remission

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5255-5255
Author(s):  
Colin Godwin ◽  
Jonathan R. Fromm ◽  
Brenda M. Sandmaier ◽  
Marco Mielcarek ◽  
Brent Wood ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Median Frequency ◽  
Prognostic Role ◽  
Support Research ◽  
Acute Myeloid

Abstract INTRODUCTION: Emerging data indicate myeloid-derived suppressor cells (MDSCs) adversely impact outcomes of patients with a variety of malignancies. However, it is less clear how MDSCs affect acute myeloid leukemia (AML) disease biology or the response of AML patients to treatment. Here, we studied a cohort of people with AML undergoing hematopoietic cell transplantation (HCT) in first complete remission (CR1) to examine the relationship between the monocytic subtype of MDSCs (M-MDSCs), pre-transplant measurable residual disease (MRD) status, and outcome after HCT. PATIENTS AND METHODS: Adults ≥18 years of age were included if they underwent first allogeneic HCT with myeloablative or nonmyeloablative conditioning for AML in CR1 from April 2006 until October 2014. Prospective MRD testing in bone marrow aspirates was performed routinely via 10-color multiparameter flow cytometry (MFC) as part of the pre-transplant work-up. Pre-transplant MFC data were used retrospectively to quantify M-MDSCs as the proportion of monocytes (identified by side scatter properties and CD14 positivity) with low or negative expression of HLA-DR. M-MDSC frequency was then expressed as a percentage of the total number of viable cells in the sample. Available combinations of antigens measured by MFC did not allow for the identification of other MDSC subsets (e.g. granulocytic MDSCs). RESULTS: We identified 349 adults undergoing allogeneic HCT for AML in CR1 for whom pre-transplant MRD testing was performed and for whom follow-up data were available. Of these, 8 had to be excluded because of insufficient MFC events available for identification of M-MDSCs. In the remaining 341 patients, M-MDSC frequency ranged from <0.001% to 6.53%, with a median of 0.18% (25th percentile: 0.06%; 75th percentile: 0.40%). Patients with lower (i.e. <median) frequency of M-MDSCs were less likely male (p=0.01) and more likely had recovered neutrophil and platelet counts (p=0.001) than patients with higher (i.e. ≥median) frequency of M-MDSCs. There was no difference with regard to all other examined characteristics (age, WBC and cytogenetic risk at diagnosis, type of AML, median CR duration before HCT, donor type, and conditioning intensity). The proportion of MRD positive ("MRDpos") patients was similar between those with lower vs. higher M-MDSC frequency (18.8 vs. 24.6%, p=0.20). Moreover, while MRD negative ("MRDneg") patients (n=267) differed statistically significantly from MRDpos patients (n=74) with regard to several characteristics such as more favorable disease risk and lower proportion of secondary AML, there was only a statistically non-significant trend toward lower M-MDSC frequency in MRDneg patients (0.16% [range <0.001-5.61%] vs. 0.22% [range <0.001-6.53%], p=0.09). The median follow-up time after HCT among all survivors was 5.8 (range, 2.0-11.4) years. The time was slightly longer for survivors with lower compared to those with higher M-MDSC frequency (6.1 [range 2.6-11.4] vs. 5.1 [range 2.0-11.3] years; p=0.0076). Stratified by the median M-MDSC frequency, the 3-year estimates of overall survival were similar for patients with lower and higher pre-HCT M-MDSCs (58.2% [95% confidence interval 50.4-65.2%] vs. 57.6% [49.8-64.7%]), as were 3-year estimates for relapse free survival (53.5% [45.7-60.7%] vs. 48.3% [40.6-55.6%]), 3-year estimates of the cumulative incidence of relapse (31.8% [24.9-38.8%] vs. 34.6% [27.6-41.8%]), and 3-year estimates of non-relapse mortality (14.7% [9.9-20.5%] vs. 17.0% [11.8-23.0%]). Analyses restricted to the subset of patients undergoing myeloablative (MA) conditioning or those undergoing MA conditioning in MRDneg remission showed qualitatively similar results. CONCLUSIONS: In the largest study to date examining the role of M-MDSCs in AML, we found no convincing evidence for a prognostic role of these cells for adults undergoing allografting in CR1. Disclosures Walter: Actinium Pharmaceuticals, Inc.: Other: Clinical trial support, Research Funding; Amgen Inc.: Other: Clinical trial support, Research Funding; Amphivena Therapeutics: Consultancy, Equity Ownership, Other: Clinical trial support, Research Funding; Aptevo Therapeutic: Consultancy, Other: Clinical trial support, Research Funding; Covagen AG: Consultancy, Other: Clinical trial support, Research Funding; Seattle Genetics, Inc.: Consultancy, Other: Clinical trial support, Research Funding; Boehringer Ingelheim Pharma GmbH & Co. KG: Consultancy; Pfizer: Consultancy.

scholarly journals Frontline Therapy with Bendamustine-Rituximab (BR) in Patients with Treatment-Naïve Waldenstrom's Macroglobulinemia Confers Similar Long-Term Outcomes to R-CVP in a Real-World Setting: A Population-Based Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1353-1353
Author(s):  
Jowon Laura Kim ◽  
Alina S. Gerrie ◽  
Kerry J. Savage ◽  
Diego Villa ◽  
David W. Scott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Gene Expression Profiling ◽  
Systemic Therapy ◽  
Expression Profiling ◽  
Research Funding ◽  
Population Based ◽  
Early Progression ◽  
Treatment Naïve

Abstract Background: Waldenström macroglobulinemia (WM) is a rare, indolent B-cell lymphoproliferative disorder. After the STiL-1 trial (Rummel MJ. Lancet. 2013;381(9873):1203-1210) demonstrated significant benefit in a subgroup analysis as well as reduced toxicity using bendamustine and rituximab (BR) compared to R-CHOP (N=41 enrolled WM patients), BR became the preferred immunochemotherapy (IC) regimen for all patients with symptomatic treatment naïve (TN) WM in British Columbia (BC) since 2014. Prior to the introduction of BR, the combination of rituximab, cyclophosphamide, vincristine, and prednisone (RCVP), was the standard of care in BC for this population since 2004, given its widespread use across a broad range of indolent B-cell lymphomas. We report a population-based analysis evaluating outcomes in TN-WM patients comparing BR with RCVP. Methods: The BC Cancer Centre for Lymphoid Cancer Database was used to identify TN-WM patients treated with BR or RCVP as their first systemic therapy between August 1, 2004 - August 1, 2020. A period of observation but no prior to systemic therapy was permitted. All patients had clinicopathologically confirmed lymphoplasmacytic lymphoma and measurable monoclonal IgM. Event-free survival (EFS) was defined as time from start of IC to progression, relapse, initiation of alternative therapy, histologic transformation, or death due to any cause. Early progression (POD24) was defined as relapse or progression, death from lymphoma, or treatment toxicity within 24 months of initiation of systemic therapy. Outcomes were compared with a historical cohort of patients treated with frontline RCVP. Responding patients were eligible to receive maintenance rituximab (MR) every 3 months for 2 years since 2006; however this was discontinued in 2020 when a subgroup analysis of the MAINTAIN trial (Rummel MJ. Blood 2019; 134 (Supplement_1): 343), showed a lack of PFS benefit after BR, coupled with safety and vaccine response concerns during the COVID-19 pandemic. Results: A total of 111 patients with WM were identified; 57 treated with BR, 54 treated with RCVP. Median age was 69 years (range 33-89) and baseline characteristics (Table 1), were well-balanced. A higher proportion of RCVP-treated patients received &gt;4 cycles of chemotherapy (81% vs 65%, p=0.049). After IC, 75 (68%) received MR, with 36 (63%) and 39 (72%) in the BR and RCVP groups respectively (p=0.3). Median follow-up from diagnosis for all living patients was 5.9 years (range 0.8-19.2), with median 4.4y vs 9.8y for BR and RCVP respectively. EFS estimates at 4-years achieved with BR were 57% (95% CI 40-71%) compared to RCVP 60% (95% CI 45-72%), p=0.5 (Figure 1). Median EFS was established for RCVP due to longer duration of follow up at 6.3 years (95% CI 3.6-11.8y). Overall survival (OS) estimates at 4-years were 74% (95% CI 57-85%) and 81% (95% CI 67-89%) for BR and RCVP patients respectively, p=0.6. Worse performance status (≥2) was the only pre-treatment factor identified as significant for inferior EFS. A sub-analysis limited to patients that received &gt;4 cycles of IC also showed no clear difference in outcomes between BR and RCVP. Median time to transformation was 6.5y (5.5-13y), with only 3 late biopsy-proven events. Early progression (POD24) has occurred in 19 (18%) patients, with inferior survival observed in patients that had an early event compared with a reference cohort (2-years event free), however this did not reach statistical significance (p=0.3) (Figure 1). Conclusion: This population-based analysis of TN-WM patients treated with upfront IC confirms the excellent outcomes that can be achieved with a finite course of therapy. In contrast to prior studies, similar outcomes were observed with RCVP and BR. Further, regardless of front-line therapy, POD24 may be associated with inferior outcome but larger studies are needed. To our knowledge, this study is the first to make a direct comparison between BR and RCVP, and one of the largest restricted to IC-treated TN-WM. This data supports RCVP as a viable option, and should serve to inform clinicians, patients, and policy makers in decision-making when considering upfront therapeutic options, and when considering indefinite alternative regimens such as BTK inhibitors. Figure 1 Figure 1. Disclosures Gerrie: AbbVie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Astrazeneca: Honoraria, Research Funding; Sandoz: Honoraria; Roche: Research Funding. Savage: Servier: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Seattle Genetics: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; Takeda: Other: Institutional clinical trial funding; AbbVie: Consultancy, Honoraria; Roche: Research Funding; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding. Villa: Roche: Honoraria; Janssen: Honoraria; Lundbeck: Honoraria; Celgene: Honoraria; Seattle Genetics: Honoraria; AbbVie: Honoraria; AstraZeneca: Honoraria; Gilead: Honoraria; NanoString Technologies: Honoraria. Scott: BC Cancer: Patents & Royalties: Patent describing assigning DLBCL COO by gene expression profiling--licensed to NanoString Technologies. Patent describing measuring the proliferation signature in MCL using gene expression profiling. ; Abbvie: Consultancy; Janssen: Consultancy, Research Funding; AstraZeneca: Consultancy; Rich/Genentech: Research Funding; Celgene: Consultancy; Incyte: Consultancy; NanoString Technologies: Patents & Royalties: Patent describing measuring the proliferation signature in MCL using gene expression profiling.. Craig: Bayer: Consultancy. Slack: Seagen: Consultancy, Honoraria. Sehn: Debiopharm: Consultancy; Novartis: Consultancy; Genmab: Consultancy. Freeman: Amgen: Honoraria; Celgene: Honoraria; Sanofi: Honoraria, Speakers Bureau; Incyte: Honoraria; Abbvie: Honoraria; Teva: Research Funding; Roche: Research Funding; Bristol Myers Squibb: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria.

Nationwide Investigation of Patient Trajectories in Mantle Cell Lymphoma - Initial Data from the Swedish MCL Complete Project

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-4
Author(s):  
Mats Jerkeman ◽  
Thorgerdur Palsdottir ◽  
Ingrid Glimelius ◽  
Alexandra Albertsson-Lindblad ◽  
Caroline Weibull ◽  
...  
Keyword(s):  
Initial Data ◽  
Mantle Cell Lymphoma ◽  
Treatment Response ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Population Based ◽  
First Line ◽  
Mantle Cell ◽  
Early Progression

Background Mantle cell lymphoma (MCL) is a B-cell malignancy, with increasing incidence. It is currently not considered curable. Although a proportion of patients obtain prolonged remission after first line chemoimmunotherapy, most patients will experience several lines of therapy. Hitherto, population based data of the complete care trajectories for patients with MCL have not been available, limiting our knowledge to that from single centre experiences. Here, we present the initial data from a nationwide attempt to collect all available data from all patients diagnosed with MCL. Methods Patients with a primary diagnosis of MCL in 2006-2018 were identified in the Swedish Lymphoma Register and followed until March 6, 2020. The register contains information about clinical characteristics, prognostic factors, primary treatment, treatment response and relapse. Information on further lines of therapy, including treatment response and progression/relapse was extracted through medical chart review in all patients. Results In total, 1411 patients were diagnosed with MCL during the period 2006-2018. Currently, complete data are available for 445 (32%). The most frequently used first line regimens were R-bendamustine (n=131, 29%) and Nordic MCL2 (n=102, 21%). 31 patients (7%) were managed with an initial watch and wait strategy. 87 patients (19%) received consolidation with an autologous stem cell transplant, and 51 (11%) patients received rituximab maintenance. After a median follow-up of 49 months (IQR 25-81), 279 patients (63%) did not experience any relapse, and the median age for patients without relapse was higher compared to the relapse group (73 vs 70 years). 166 patients (37%) experienced a first relapse or progression. The most frequently used second line regimen was R-bendamustine (n=49, 30%). 102 (21%) and 51 (11%) experienced a second or third relapse/progression, respectively. The median PFS after 1st (PFS-1), 2nd, (PFS-2), 3rd (PFS-3) and 4th (PFS-4) lines of therapy were 40, 11, 6, and 4 months. Patients with early progression, defined as a PFS-1 &lt;24 months (POD24-1) had an inferior outcome (median OS of 23 vs. 101 months) compared to patients with a later relapse. Similarly, patients with a POD24-2 had an inferior outcome compared to patients with PFS-2 ³24 months (median OS 8.4 vs 61 months). Conclusion In this population-based series, mainly treated with conventional chemoimmunotherapy, 63% of patients diagnosed with MCL did not experience relapse/progression after a median follow-up of 40 months - due to death before relapse or continuous remission. In addition, PFS and OS continue to drop with successive lines of therapies. Early progression, both after 1st and after 2nd line therapy is associated with markedly impaired OS -identifying patient populations in need of novel treatment strategies. Figure 1 A. Progression-free survival (PFS) in 445 patients with mantle cell lymphoma (MCL) diagnosed in Sweden 2006-2018 according to first line regimen. B. Overall survival (OS) according to time to relapse (PFS -1 &lt; 24 months or &gt;24 months). Figure Disclosures Jerkeman: Abbvie: Research Funding; Celgene: Research Funding; Gilead: Research Funding; Janssen: Research Funding; Roche: Research Funding. Weibull:Janssen Cilag: Research Funding. Smedby:Celgene: Consultancy; Janssen: Research Funding; Takeda: Research Funding.

scholarly journals Evaluation of International Working Group 2006 Response Criteria in Patients with Higher-Risk Myelodysplastic Syndromes (HR-MDS) Treated with Hypomethylating Agent Monotherapy in the Frontline Setting

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3701-3701
Author(s):  
Jan Philipp Bewersdorf ◽  
Wei Wei ◽  
Anna Jaiani ◽  
Prital Patel ◽  
Rajni Mehta ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Trials ◽  
Myelodysplastic Syndromes ◽  
Working Group ◽  
Research Funding ◽  
Response Criteria ◽  
The Impact ◽  
Support Research

Abstract Introduction: Monotherapy with hypomethylating agents (HMA) remains the standard of care for patients (pts) with myelodysplastic syndromes (MDS). Response in MDS is based on the modified International Working Group (IWG) 2006 criteria. Prior studies focusing on unselected MDS pts showed that achieving a complete remission (CR) was associated with favorable overall survival (OS). However, the association of other outcomes with OS was less clear and only 20% of HMA-treated MDS pts achieve a CR. For example, pts who achieved &lt;5% bone marrow (BM) blasts are currently classified as marrow CR (mCR), which has not been associated with OS improvement. Therefore, interpreting the significance of mCR reported in various clinical trials is challenging. Clinically meaningful reduction in bleeding or infectious complications can occur at improvements in absolute neutrophil count (ANC) and platelet counts that do not meet the current thresholds used for CR (ANC ≥1.0 × 10 9/L, platelets ≥100 × 10 9/L, and Hb &gt;11 g/dL). To avoid missing clinically meaningful benefits when studying new drugs in clinical trials, a clearly defined response criterion that is less stringent than CR but still captures clinically meaningful hematologic improvement (HI) is needed. Here we sought to evaluate the impact of current IWG 2006 response criteria as well as CRh on OS of pts with HR-MDS treated with frontline HMA monotherapy. Methods: We included all adult (≥18 years) MDS pts treated with frontline HMA (azacitidine [AZA], decitabine [DEC], or ASTX727) monotherapy between 1/1/2012 and 12/31/2020 at Yale University. We decided to use HMA monotherapy as it is the standard care for HR-MDS and to minimize the impact of therapy choice confounding the association of achieved response with OS. Pts were excluded if they received prior treatments for MDS aside from erythropoiesis-stimulating agents and if no baseline with at least one follow-up BM study were available for response assessment. We collected patient and disease characteristics (transfusion burden, IPSS/IPSS-R score, cytogenetics, molecular studies) at baseline. Best responses were assessed based on IWG 2006 criteria for MDS. We defined CRh as &lt;5% BM blasts, platelets ≥50 × 10 9/L, ANC ≥0.5 × 10 9/L and no peripheral blood blasts. We followed pts until death or last follow-up and recorded dates of allogeneic hematopoietic cell transplant (HCT) if applicable. Date of data cut-off for survival status was 5/31/2021. We performed Kaplan-Meier analysis to estimate the duration of overall survival and we used log rank test to test the difference in OS between subgroups of pts. Multiple comparisons were adjusted using the Bonferroni method. Results: A total of 100 pts was included in this analysis (Table 1). Median age was 68 years (yrs; range, 23 - 86), 60% were males, and 79% and 18% of pts received AZA and DEC, respectively. Median number of HMA cycles was 6 (interquartile range [IQR]: 4-10), and 33 pts (33%) underwent HCT. During follow-up, 46 pts (48%) progressed to AML. At a median follow-up of 1.5 yrs (IQR: 0.9 - 2.3 yrs), median OS for the entire pt cohort was 1.9 yrs (Figure 1). OS by response category is shown in Table 2. Median OS was not reached for patients who achieved a CR (95% CI: not reached [NR] - NR) as compared to 1.9 yrs (95% CI: 1.5 yrs - NR) and 2.0 yrs (95% CI: 1.2 yrs - NR) among pts with mCR + HI and mCR without HI, respectively. Median OS among patients with stable disease (SD) was similar (2.0 yrs [95% CI: 1.5 yrs - NR]). Finally, we explored the prognostic value of CRh and found a median OS of 1.9 yrs (95% CI: 1.5 yrs - NR), which appeared comparable to mCR +/- HI or SD. Similar results were found with censoring at time of HCT (Figure 2). Discussion: In this retrospective analysis of MDS pts treated with HMA monotherapy in the frontline setting, achieving CR as best response was associated with improved OS compared with mCR +/- HI and SD. However, as the numbers were small these results should be interpreted with caution, and other clinically relevant outcomes such as freedom of transfusion, infectious or bleeding complications, and patient-reported outcomes were not captured in the current analysis. Our results also apply only to MDS pts treated with HMA monotherapy in the frontline setting. The prognostic implications of CRh need to be evaluated in larger patient cohorts. To overcome these limitations, we are currently in the process of expanding the study to a much larger multi-center, international analysis. Figure 1 Figure 1. Disclosures Neparidze: Eidos Therapeutics: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Research Funding; Janssen: Research Funding. Shallis: Curis: Divested equity in a private or publicly-traded company in the past 24 months. Podoltsev: PharmaEssentia: Honoraria; Pfizer: Honoraria; CTI BioPharma: Honoraria; Blueprint Medicines: Honoraria; Incyte: Honoraria; Bristol-Myers Squib: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Brunner: GSK: Research Funding; Aprea: Research Funding; Keros Therapeutics: Consultancy; Agios: Consultancy; AstraZeneca: Research Funding; Novartis: Consultancy, Research Funding; Acceleron: Consultancy; Takeda: Consultancy, Research Funding; BMS/Celgene: Consultancy, Research Funding; Janssen: Research Funding. Zeidan: AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding; Gilead: Consultancy, Other: Clinical Trial Committees; Epizyme: Consultancy; Amgen: Consultancy, Research Funding; BioCryst: Other: Clinical Trial Committees; Incyte: Consultancy, Research Funding; Boehringer Ingelheim: Consultancy, Research Funding; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; Acceleron: Consultancy, Research Funding; Agios: Consultancy; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; Genentech: Consultancy; Jasper: Consultancy; ADC Therapeutics: Research Funding; Jazz: Consultancy; Astex: Research Funding; Daiichi Sankyo: Consultancy; Kura: Consultancy, Other: Clinical Trial Committees; Aprea: Consultancy, Research Funding; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; Geron: Other: Clinical Trial Committees; AstraZeneca: Consultancy; Pfizer: Other: Travel support, Research Funding; BeyondSpring: Consultancy; Ionis: Consultancy; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; Janssen: Consultancy; Astellas: Consultancy.

scholarly journals Cost-Effectiveness of Liposomal Cytarabine-Daunorubicin (CPX-351) Compared to Conventional Cytarabine-Daunorubicin Chemotherapy in Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 113-113
Author(s):  
Jan Philipp Bewersdorf ◽  
George Goshua ◽  
Kishan K Patel ◽  
Rory M. Shallis ◽  
Nikolai Podoltsev ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cost Effectiveness ◽  
Research Funding ◽  
Cost Effective ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Inpatient Setting ◽  
Consolidation Therapy ◽  
Phase Iii Trial ◽  
Support Research

Abstract Introduction: A randomized phase III trial demonstrated improved overall survival (OS) and event-free survival (EFS) for older patients diagnosed with therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) treated with a liposomal formulation of daunorubicin-cytarabine (CPX-351) when compared with 7+3 induction and consolidation therapy, a previous standard of care. Based on those results, CPX-351 was approved in 2017 in the United States (US) for adults with newly diagnosed t-AML and AML-MRC irrespective of age. However, the health economic implications of CPX-351 from a US payer perspective are not well-characterized. Methods: We constructed a partitioned survival analysis based on the data from the original phase III trial (Lancet et al. JCO 2018) and subsequent updates (Lancet et al. Lancet Haematology 2021) and post-hoc analyses from the landmark trial (Villa et al. JME 2019). Newly diagnosed AML patients at a median age of 68 years entered the model with active AML and received either CPX-351 or 7+3 induction and consolidation therapy followed by allogeneic hematopoietic cell transplant (allo-HCT) for some patients. Parametric survival distributions were fitted using patient-level data recreated from the Kaplan-Meier curves and at-risk tables for EFS and OS for both study arms. Log-logistic distributions demonstrated the best fit and were chosen for this model. Frequency and setting (inpatient vs outpatient) of re-induction and consolidation therapy were used as outlined in the original study. Costs and practice patterns of salvage therapy, receipt of allo-HCT, supportive care, and incidence of complications were derived from the original trial or published literature (Table). If available, costs for the Medicare population rather than commercially insured patients were used. For the CPX-351 arm, the maximum new technology add-on payment granted by the Centers for Medicare & Medicaid Services for fiscal year 2020 was added to the costs of inpatient induction and consolidation therapy in the 7+3 arm. Costs were adjusted for inflation to 2020 US dollars using the personal consumption expenditure health index. Previously published utilities were used and measured in quality-adjusted life years (QALYs). Costs and utilities were discounted by 3% annually (range 3-5% in one-way sensitivity analysis) and modelled over a 10-year time horizon. Model outputs were used to calculate the incremental cost-effectiveness ratio (ICER) for CPX-351 over 7+3. A willingness-to-pay (WTP) threshold of $150,000/QALY gained was used to determine cost-effectiveness. One-way sensitivity analyses were performed with utility values varied with a 10% range and all other variables across a 50% range. In probabilistic sensitivity analyses using 10,000 Monte Carlo simulations, beta distributions were used to describe probabilities and utilities, while gamma distributions were used for costs. Results: CPX-351 and 7+3 were associated with lifetime costs of $371,482 and $256,415, respectively, for an incremental cost of $115,066 with CPX-351. CPX-351 resulted in an incremental gain of 0.49 QALYs compared to 7+3 (CPX-351: 1.11 QALYs vs 7+3: 0.62 QALYs) resulting in an ICER of $231,563/QALY gained in the base case analysis. In one-way sensitivity analyses our model was most sensitive to the probability of receiving allo-HCT in either arm (Figure). In threshold analyses, a reduction of the CPX-351 add-on charge in the inpatient setting by 70.4% (from $47,353 to $14,004) would lower the ICER below the WTP threshold of $150,000/QALY. Probabilistic sensitivity analysis yielded a median ICER of $222,894 (95% credible interval: $142,863 - $313,289) with 7+3 favored in 96.4% of 10,000 iterations at a WTP threshold of $150,000. Conclusion: Use of CPX-351 under the current pricing model is unlikely to be cost-effective for most older patients with t-AML/AML-MRC who resemble those enrolled in the clinical trial. A reduction by 70.4% for the CPX-351 add-on charge in the inpatient setting would be necessary to lower the ICER below the conventional WTP threshold of $150,000/QALY. Higher rates of allo-HCT and outpatient consolidation with CPX-351 did not lead to gains in clinical utility or cost reductions substantial enough to make CPX-351 cost-effective. The implications of a potential outpatient administration of CPX-351 induction on its cost-effectiveness require additional studies. Figure 1 Figure 1. Disclosures Shallis: Curis: Divested equity in a private or publicly-traded company in the past 24 months. Podoltsev: PharmaEssentia: Honoraria; Blueprint Medicines: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; CTI BioPharma: Honoraria; Bristol-Myers Squib: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Huntington: Bayer: Honoraria; Thyme Inc: Consultancy; Servier: Consultancy; Novartis: Consultancy; SeaGen: Consultancy; AstraZeneca: Consultancy, Honoraria; Genentech: Consultancy; TG Therapeutics: Research Funding; Flatiron Health Inc.: Consultancy; DTRM Biopharm: Research Funding; AbbVie: Consultancy; Pharmacyclics: Consultancy, Honoraria; Celgene: Consultancy, Research Funding. Zeidan: Astex: Research Funding; Amgen: Consultancy, Research Funding; Epizyme: Consultancy; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; Aprea: Consultancy, Research Funding; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; AstraZeneca: Consultancy; Janssen: Consultancy; Daiichi Sankyo: Consultancy; Jasper: Consultancy; Astellas: Consultancy; Genentech: Consultancy; Geron: Other: Clinical Trial Committees; Agios: Consultancy; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; BioCryst: Other: Clinical Trial Committees; Pfizer: Other: Travel support, Research Funding; Kura: Consultancy, Other: Clinical Trial Committees; Incyte: Consultancy, Research Funding; BeyondSpring: Consultancy; Gilead: Consultancy, Other: Clinical Trial Committees; Ionis: Consultancy; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; ADC Therapeutics: Research Funding; Jazz: Consultancy; Boehringer Ingelheim: Consultancy, Research Funding; Acceleron: Consultancy, Research Funding; AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding.

scholarly journals The Association of Abnormal Liver Enzymes with All-Cause and Cause-Specific Mortality: A Large Prospective Population-Based Study

2019 ◽  
Author(s):  
Shadi Kolahdoozan ◽  
Nazgol Motamed-Gorji ◽  
Maryam Sharafkhah ◽  
Sadaf G. Sepanlou ◽  
Pedram Afshar ◽  
...  
Keyword(s):  
Cancer Mortality ◽  
Total Population ◽  
Liver Enzymes ◽  
Total Sample ◽  
Population Based ◽  
Sensitivity Analyses ◽  
All Cause Mortality ◽  
Cox Proportional Hazard Regression ◽  
Cvd Mortality

Abstract Background: While the association of elevated levels of liver enzymes (ALT, AST, ALP and GGT) with mortality has been suggested in many studies, evidence of their association appears to be contradictory. The current study aims to investigate the associations of entire ranges of serum liver enzymes with mortality in a large cohort of adults. Methods: In the current study we used the data of repeated measurement phase in Golestan Cohort Study, which was conducted from 2010 to 2012. All liver enzyme levels were categorized into their quintile values, and the association of liver enzymes with mortality rates were evaluated using Cox proportional hazard regression models. Sensitivity analyses were performed by excluding data of first follow-up year, and patients with history of cardiovascular disease (CVD), cancer or viral hepatitis. Results: We included 11,106 individuals with mean age of 56.22 (±7.97) years, 46.2% male. Median follow-up period was 7 years. In the total population, ALT demonstrated a U-shaped association with all-cause mortality; whereas AST showed no significant association. ALP and GGT had linear and positive associations with overall mortality in the total population. CVD-mortality showed associations with low ALT (aHR=1.53, 95% CI: 1.1-2.2), high ALP (aHR=1.79, 1.3-2.6) and high GGT (aHR=2.0, 1.4-2.9). Cancer-mortality was associated with high ALP (aHR=1.9, 1.2-2.9, while GGT had a U-shaped association with cancer mortality, with the middle category (Q3) associated with the lowest cancer-mortality risk (aHR=0.58, 0.4-0.9). High ALT and high AST were associated with cancer-mortality in total sample as well; although, these associations disappeared after the sensitivity analysis. Conclusion: Both low and high levels of ALT are associated with increased all-cause mortality, while only high levels of ALP and GGT have positive associations with all-cause mortality. High levels of all four liver enzymes are associated with cancer mortality. However, only the high levels of ALP and GGT are associated with CVD mortality. Evidence implies that abnormal liver enzymes may be manifestations of metabolic syndrome, CVD, and cancers rather than being their precursors. Yet, they may be useful markers for predicting the survival of patients.

scholarly journals Treatment Utilization and Characteristics Among Patients with Higher-Risk Myelodysplastic Syndromes According to Hypomethylating Agent Use

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5030-5030
Author(s):  
Amer M. Zeidan ◽  
Victoria Divino ◽  
Mitch DeKoven ◽  
Drishti Shah ◽  
Elizabeth Wang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Supportive Care ◽  
Research Funding ◽  
Treatment Utilization ◽  
Leadership Position ◽  
Newly Diagnosed ◽  
Comorbidity Burden ◽  
The Us ◽  
Support Research

Abstract Introduction: Hypomethylating agents (HMAs) are standard of care treatment for patients with higher-risk myelodysplastic syndromes (HR-MDS) who are ineligible for stem-cell transplantation or intensive chemotherapy. Until recently, approved HMAs included intravenous or subcutaneous azacitidine and decitabine, which should be administered for a minimum of 4-6 cycles to elicit response in the absence of progression or unacceptable toxicity. In real-world clinical practice, underutilization of HMA therapy has been documented; however, prior estimates have utilized data preceding 2016. The study objectives were to understand recent treatment utilization and characteristics among patients newly diagnosed with HR-MDS in the United States (US). Methods: This retrospective observational study utilized the IQVIA PharMetrics ® Plus database which comprises adjudicated claims for more than 190 million unique patients across the US. Adult patients newly diagnosed with HR-MDS from July 1, 2016 through December 31, 2019 were included. Patients had ≥1 inpatient claim or ≥2 outpatient claims &gt;60 days apart with diagnosis codes for high grade MDS lesions and/or refractory anemia with excess blasts (RAEB), and continuous enrollment for 6 months prior to and ≥180 days following the index date (index date = first diagnosis claim). Patients had a variable follow-up period up to 1 year post-index, and were followed through June 30, 2020. Patient characteristics at baseline, and treatment utilization based on observed MDS-related therapy (HMAs and supportive care), over the variable follow-up period were evaluated. Results: A total of 371 patients were included; the mean age of patients at baseline was 69.2 years and 57.7% were male. Of these, 61 (16.4%) patients received no HMA and no supportive care over the variable follow-up period following diagnosis. Half (n=182, 49.1%) received no HMA but received supportive care, and the remainder (n=128, 34.5%) received HMA therapy over the variable follow-up period; 45 (12.1%) received decitabine as the first HMA in a mean of 89.2 days from diagnosis, and 83 (22.4%) received azacitidine as the first HMA in a mean of 51.1 days from diagnosis (Table). Patients receiving no HMA therapy but with supportive care were older (mean age 70.6 years; 45.6% aged ≥75 years) and had higher comorbidity burden (mean Charlson Comorbidity Index [CCI] 2.5) than the other cohorts (mean age 66.6-68.8 years; 24.4-37.7% aged ≥75 years; CCI 1.2-2.0). For example, a higher proportion of patients receiving no HMA therapy but with supportive care had baseline renal disease (21.4%) compared to the other cohorts (4.9-15.6%). Patients receiving no HMA or supportive care in this study had a similar mean age compared to those who received HMAs (68.8 vs 66.6-68.0 years), but tended to have lower comorbidity burden (CCI 1.2 vs 1.9-2.0). Conclusions: In this real-world study using contemporary data, utilization of HMA therapy among patients with HR-MDS in the US was low, with only around one-third of patients receiving HMAs. Patients who did not receive HMAs but received supportive care tended to be older and have higher comorbidity burden than those who received HMAs, suggesting potential barriers for physicians in prescribing HMAs to older, frailer patients. Figure 1 Figure 1. Disclosures Zeidan: Pfizer: Other: Travel support, Research Funding; Jazz: Consultancy; Jasper: Consultancy; AstraZeneca: Consultancy; Janssen: Consultancy; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; Ionis: Consultancy; Kura: Consultancy, Other: Clinical Trial Committees; Incyte: Consultancy, Research Funding; Gilead: Consultancy, Other: Clinical Trial Committees; Genentech: Consultancy; Epizyme: Consultancy; Daiichi Sankyo: Consultancy; Geron: Other: Clinical Trial Committees; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; Boehringer Ingelheim: Consultancy, Research Funding; BioCryst: Other: Clinical Trial Committees; BeyondSpring: Consultancy; Astex: Research Funding; Astellas: Consultancy; Aprea: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Agios: Consultancy; ADC Therapeutics: Research Funding; Acceleron: Consultancy, Research Funding; AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding. Divino: IQVIA: Current Employment, Other: IQVIA received funding for this study from Epstein Health in connection with this study. DeKoven: IQVIA: Current Employment, Other: IQVIA received funding for this study from Epstein Health in connection with this study. Shah: IQVIA: Current Employment, Other: IQVIA received funding for this study from Epstein Health in connection with this study. Wang: IQVIA: Current Employment, Other: IQVIA received funding for this study from Epstein Health in connection with this study. Bey: Taiho Oncology: Current Employment. Salimi: Taiho Oncology: Current Employment. Epstein: Epstein Health: Current Employment; Fate Therapeutics: Other: Holds leadership position; Veracyte: Other: Holds leadership position; Illumina: Other: Holds leadership position; Merck: Consultancy; Radius Health: Consultancy; Halozyme: Consultancy; Intra-Cellular Therapies: Consultancy; Taiho Oncology: Consultancy; Otsuka: Consultancy.

scholarly journals Age-stratified outcomes of bioprosthetic and mechanical aortic valve replacements in an Australian cohort of 13 377 patients

2020 ◽  
Vol 2 (1) ◽  
pp. e000036
Author(s):  
Oluwadamisola Temilade Sotade ◽  
Michael Falster ◽  
Leonard N Girardi ◽  
Sallie-Anne Pearson ◽  
Louisa R Jorm
Keyword(s):  
Aortic Valve ◽  
Age Groups ◽  
Mechanical Valve ◽  
Population Based ◽  
Mortality Data ◽  
Surgical Aortic Valve Replacement ◽  
Major Hemorrhage ◽  
All Cause Mortality ◽  
Rate Ratios

ObjectivesTo quantify age-stratified outcomes of bioprosthetic valve (BV) and mechanical valve (MV) surgical aortic valve replacement (AVR) in Australian patients.DesignRetrospective cohort study using population-based linked hospital morbidity and mortality data.SettingPublic and private hospitals.ParticipantsPatients aged 18 years and over undergoing AVR from 2001 to 2013, stratified by age (18–64 years; 65+ years).Main outcome measuresAge-standardized index AVR rates; rates and multivariable-adjusted (age, sex, Charlson Comorbidity Index) incidence rate ratios (IRRs) for reoperation, incident cardiovascular events (hospitalization or death for acute myocardial infarction (AMI), stroke, major hemorrhage or thromboembolism) and mortality (cardiovascular and all-cause).ResultsOur cohort comprised 13 377 patients, of whom 3464 (26%) were aged 18–64 years. Annual age-standardized AVR rates increased by 2.7% with BV implants increasing in both age groups. After 5 years of follow-up, patients implanted with BV had lower rates of stroke (IRR: 0.40, 95% CI 0.27 to 0.60) and hemorrhage (IRR: 0.36, 95% CI 0.26 to 0.50). Among patients 65+ years, those implanted with BV had lower rates of AMI, hemorrhage, and cardiovascular and all-cause mortality than those implanted with MV (IRR: 0.71, 95% CI 0.53 to 0.96; IRR: 0.77, 95% CI 0.62 to 0.95; IRR: 0.80, 95% CI 0.69 to 0.92 and IRR: 0.85, 95% CI 0.74 to 0.97, respectively). After 6–10 years of follow-up, reoperation rates among patients 18–64 years were markedly higher in those implanted with BV compared with MV (IRR: 5.48, 95% CI 2.38 to 12.62) and rates of AMI were lower among patients implanted with BV compared with MV (IRR: 0.49, 95% CI 0.26 to 0.94). Among patients 65+ years rates of cardiovascular and all-cause mortality remained significantly lower for patients implanted with BV compared with MV.ConclusionsThis study provides real-world evidence of AVR use and outcomes. Use of BV implants is increasing irrespective of age. Valve choice in younger patients requires thorough evaluation of patient factors influencing both short-term outcomes and longer-term risks of reoperation, stroke and hemorrhage.

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