Excess Mortality Among 10-Year Survivors of Classical Hodgkin Lymphoma in Adolescents and Young Adults

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 694-694
Author(s):  
Ana Xavier ◽  
Luciano J. Costa
Keyword(s):  
Cardiovascular Disease ◽  
Young Adults ◽  
Cardiovascular Diseases ◽  
Hodgkin Lymphoma ◽  
Causes Of Death ◽  
Excess Mortality ◽  
Mortality Rates ◽  
Classical Hodgkin Lymphoma

Background: Adolescents and young adults (AYA) surviving classical Hodgkin Lymphoma (cHL) commonly face significant treatment-related morbidity that can result in premature death. It is not known if changes in therapy in recent years have resulted in reduction of excess mortality among long-term survivors of AYA-cHL. Methods: We used data from the National Cancer Institute's Surveillance Epidemiology and End Results program (SEER-18) to determine the excess mortality rate (EMR) for 10-year survivors of cHL. We included patients age 15-39 years diagnosed with cHL as first malignant neoplasm from 1993 until 2003. Cases reported from death certificates or autopsy only were excluded. Follow up was updated at the end of 2013. EMR was calculated using the difference between the observed mortality in the cohort of interest and the adjusted expected mortality among age, gender and race-matched individuals in the general population. Results: A total of 6,480 cases of cHL were included in the analysis with median follow up of 42.5 months. Median age of patients was 27 years at the time of diagnosis, 3,172 (48.9%) were male, 4,405 (68%) had stage I or II, 1,750 (27%) had stage III or IV, and in 325 (5%) cases stage was not available. Most patients were non-Hispanic white (4,783, 73.8%), 761 (11.7%) Hispanic, 615 (9.5%) non-Hispanic black, 276 (4.3%) other ethnicity, and 45 (0.7%) unknown. Five thousand and sixty eight (78.2%) had nodular sclerosis cHL, 616 (9.5%) had mixed-cellularity cHL, 606 (9.4%) had cHL non-otherwise specified, 153 (2.4%) had lymphocyte-rich cHL, and 37 (0.57%) had lymphocyte depleted cHL. The 15-year, 18-year, and 20-year EMR for 10-year survivors was 2.19% (95% C.I, 1.69%-2.86%), 3.48% (95% C.I. 2.57%-4.64%) and 4.07% (95% C.I. 2.53%-6.52%), respectively. EMR among 10 year AYA cHL survivors with diagnosis between 1993 and 2003 was substantially improved when compared to a similar cohort of 5,870 survivors with diagnosis between 1973 and 1992 (Figure 1). EMR at 15 and 18 years of diagnosis was higher among survivors of stage III-IV cHL than among survivors of stages I-II (Figure 2a), and higher at 15 years among males than female survivors (Figure 2b). Use of radiation therapy for early stage disease did not seem to affect the risk of excess mortality among 10-year survivors (Table). Causes of death were similar for stages I-II vs. stages III-IV. Most common causes of death were second malignancy (27.2%), cardiovascular disease (19%), and Hodgkin lymphoma (18.5%). Among male survivors there was a higher proportion of deaths due to cardiovascular disease (23.7% vs. 11.5%, p <0.038). Conclusion: Excess mortality rates for 10-year survivors of AYA-cHL has decreased with adoption of less toxic therapies. However, mortality rates continue high for several years for long term AYA HL survivors, mainly due to second malignancies and cardiovascular diseases. Less toxic therapies, control of cardiovascular diseases and implementation of cancer prevention programs for survivors of AYA-cHL are needed. Table. Table. Disclosures Costa: Sanofi: Honoraria, Research Funding.

scholarly journals Excess mortality among 10-year survivors of classical Hodgkin lymphoma in adolescents and young adults

2017 ◽  
Vol 93 (2) ◽  
pp. 238-245 ◽  
Author(s):  
Ana C. Xavier ◽  
Narendranath Epperla ◽  
Jeffrey W. Taub ◽  
Luciano J. Costa
Keyword(s):  
Young Adults ◽  
Hodgkin Lymphoma ◽  
Excess Mortality ◽  
Adolescents And Young Adults ◽  
Classical Hodgkin Lymphoma

Changes In The Use Of Radiation Therapy Among Adolescents and Young Adults With Early Stage Classical Hodgkin Lymphoma: Implications For Survival and Risk Of Secondary Malignancies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 722-722
Author(s):  
Ana Xavier ◽  
Luciano J Costa
Keyword(s):  
Young Adults ◽  
Multivariate Analysis ◽  
Radiation Therapy ◽  
Hodgkin Lymphoma ◽  
Cumulative Incidence ◽  
Early Stage ◽  
Stage I ◽  
Secondary Malignancies ◽  
Classical Hodgkin Lymphoma

Abstract Background Early stage classical Hodgkin lymphoma (HL) is a highly curable disease with the combined use of chemotherapy and radiation therapy (RT). There has been a recent trend to abandon RT, driven mostly by concerns of development of secondary malignancies (SMN). However, it is unknown whether the omission of RT in adolescents and young adults (AYA) with early stage HL affects survival and the risk of developing SMN. Methods We used data from the National Cancer Institute's Surveillance Epidemiology and End Results program (SEER-13) to determine the overall survival (OS) and the risk of SMN among AYA with early stage HL treated or not with radiation therapy. Inclusion criterion was the diagnosis of stage I or II HL in the period of 1995-2010 as first malignant neoplasm among patients age 13 to 40 years. Patients with less than 6 months of follow up and patients with unknown use of RT were excluded. Follow up was updated to the end of 2012 (November 2012 submission). Cases were divided in two “eras”, 1995-2002 and 2003-2010, with the latter being expected to reflect changes in the use of RT. The impact of the era, RT, age, race, gender, and stage on survival were accessed utilizing multivariate analysis. Cumulative incidence of SMN among early stage HL survivors was calculated using a competing risk model, treating death from any cause in absence of SMN as the competing risk. Results A total of 5,336 early stage HL cases were included in the analysis with median follow up of 89 months (range 7-191). Median age of patients was 27 years, 2,459 (46%) were male, 1,327 (24.8%) had stage I, 512 (9.7%) had classical HL non otherwise specified, 4,231 (79.2%) had nodular sclerosing HL, 442 (8.3%), had mixed-cellularity HL, 130 (2.4%) had lymphocyte-rich HL, and 21 (0.4%) had lymphocyte depleted HL. Most patients were white (4,438; 83.2%), 513 (9.6%) black, 337 (6.4%) other ethnicity, and 44 (0.8%) unknown. There where 2,793 patients in the 1995-2002 era and 2,542 patients in the 2003-2010 era. Radiation was included in the initial treatment of 1,659 (59.4%) patients in the former and 1,351 (53%) patients in the latter era (P<0.001). Factors associated with use of RT were earlier era, white race and stage II HL. Within the 1995-2002 era, there was a trend towards better survival among patients treated with RT (5-year survival 95.0% vs. 93.6%, P=0.058). In the 2003-2010 cohort survival was superior among patients treated with RT (5-year survival 97.3% vs. 95.9%, P=0.008). In multivariate analysis, diagnosis of HL in the 1995-2002 era (HR=1.73, 95% C.I. 1.31-2.28, P < 0.001), black race (HR= 2.18, 95% C.I. 1.63-2.91, P <0.001), male sex (HR=1.55, 97% C.I. 1.24-1.93, P < 0.001), and omission of RT (HR=1.31, 95% C.I. 1.05-1.64, P=0.017) were associated with higher mortality. The cumulative incidence of SMN was not significantly different between patients treated or not with radiation, while the risk of death was higher among patients not treated with RT (Figure). Conclusion There has been a reduction in utilization of RT among AYA with early stage HL in the US. Omission of RT was associated with increased overall mortality but no reduction in incidence of SMN and should not be adopted outside clinical trials. Disclosures: No relevant conflicts of interest to declare.

Temporal Trends in Mortality From Diseases of the Circulatory System After Treatment for Hodgkin Lymphoma: A Population-Based Cohort Study in Sweden (1973 to 2006)

2013 ◽  
Vol 31 (11) ◽  
pp. 1435-1441 ◽  
Author(s):  
Sandra Eloranta ◽  
Paul C. Lambert ◽  
Jan Sjöberg ◽  
Therese M.L. Andersson ◽  
Magnus Björkholm ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Causes Of Death ◽  
Excess Mortality ◽  
Temporal Trends ◽  
Circulatory System ◽  
Population Based ◽  
Competing Causes ◽  
Treatment Related Mortality ◽  
Related Mortality

PurposeHodgkin lymphoma (HL) survival in Sweden has improved dramatically over the last 40 years, but little is known about the extent to which efforts aimed at reducing long-term treatment-related mortality have contributed to the improved prognosis.MethodsWe used population-based data from Sweden to estimate the contribution of treatment-related mortality caused by diseases of the circulatory system (DCS) to temporal trends in excess HL mortality among 5,462 patients diagnosed at ages 19 to 80 between 1973 and 2006. Flexible parametric survival models were used to estimate excess mortality. In addition, we used recent advances in statistical methodology to estimate excess mortality in the presence of competing causes of death.ResultsExcess DCS mortality within 20 years after diagnosis has decreased continually since the mid-1980s and is expected to further decrease among patients diagnosed in the modern era. Age at diagnosis and sex were important predictors for excess DCS mortality, with advanced age and male sex being associated with higher excess DCS mortality. However, when accounting for competing causes of death, we found that excess DCS mortality constitutes a relatively small proportion of the overall mortality among patients with HL in Sweden.ConclusionExcess DCS mortality is no longer a common source of mortality among Swedish patients with HL. The main causes of death among long-term survivors today are causes other than HL, although other (non-DCS) excess mortality also persists for as long as 20 years after diagnosis, particularly among older patients.

scholarly journals Death, Hospitalization, and Economic Associations among Incident Hemodialysis Patients with Hematocrit Values of 36 to 39%

2001 ◽  
Vol 12 (11) ◽  
pp. 2465-2473 ◽  
Author(s):  
ALLAN J. COLLINS ◽  
SUYING LI ◽  
WENDY ST. PETER ◽  
JIM EBBEN ◽  
TRICIA ROBERTS ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cox Regression ◽  
Prospective Trial ◽  
Mortality Rates ◽  
Hemodialysis Patients ◽  
Target Range ◽  
Economic Evaluations ◽  
Hospitalization Rates

Abstract. Anemia treatment with epoetin has led to dramatic increases in hematocrit levels since 1989. Studies have demonstrated that morbidity and mortality rates are lower when hematocrit values are within the Disease Outcomes Quality Initiative (DOQI) target range (33 to 36%). Recently, clinical studies demonstrated that patients without cardiovascular disease exhibited lower morbidity rates and improved cognitive function with hematocrit values of >36%. One prospective trial, in contrast, demonstrated that normal hematocrit values among patients with cardiac disease were associated with higher mortality rates. These conflicting results have led to concerns regarding the risks and benefits associated with hematocrit values between 36 and 42%. To address these concerns, a recent cohort of 1996 to 1998 incident hemodialysis patients was studied, with assessments of the risks of death and hospitalization and the medical costs associated with hematocrit values of >36%. Patients survived at least 9 mo after dialysis initiation, and comorbidity, disease severity, and hematocrit levels were determined for months 4 to 9. Patients were grouped on the basis of hematocrit values,i.e., <30, 30 to <33, 33 to <36, 36 to <39, or ≥39%, with 1 yr of follow-up monitoring. A Cox regression model was used to evaluate all-cause and cause-specific mortality and hospitalization rates. The economic evaluations included analyses with Medicare Parts A and B allowable expenditures as the dependent variable and the same clinical characteristics as independent variables. For patients with hematocrit values of ≥36%, mortality rates were not different, hospitalization rates were 16 to 22% lower, and expenditures were 8.3 to 8.5% less, compared with patients with hematocrit values of 33 to <36%. These observations do not demonstrate causality. Additional long-term studies are needed to assess the risks of higher hematocrit values among all patients and patients with cardiovascular disease.

Final Report of a Phase-II Study of Rituximab Plus ABVD for Patients with Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma.: Results of Long Follow up and Comparison to Institutional Historical Data.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1680-1680 ◽  
Author(s):  
Amanda R Copeland ◽  
Yumei Cao ◽  
Michelle Fanale ◽  
Luis Fayad ◽  
Peter McLaughlin ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Historical Data ◽  
Stage Iii ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Classical Hodgkin Lymphoma ◽  
Bulky Disease ◽  
Long Term Follow Up

Abstract Abstract 1680 Poster Board I-706 We previously reported (Wedgwood et al, ASH, 2007) improvement in event free survival (EFS) using Rituximab+ABVD (RABVD) in newly diagnosed patients with advanced stage classical Hodgkin lymphoma (HL) when compared to the previously published historical data from the International Prognostic Score (IPS) project using standard ABVD (Hasenclever et. Al, NEJM, 1998). The purpose of this report is to provide a final update on the EFS with long term follow up of patients who received RABVD. In addition, because of the potential difference in the EFS reported by the IPS project and a single institution results, we provide a new analysis comparing our RABVD data to that of historical data from our institution. After IRB approval, we conducted a retrospective data analysis on patients with advanced HL treated at our center with ABVD from February 1996 to May 2006. Information was collected for the IPS factors: age, stage, gender, hemoglobin, white blood cell count, albumin, and lymphocyte count. 104 consecutive patients who met the eligibility criteria for the RABVD study were identified, and were evaluable for response with at least 2 year follow up. Median age was 35 years old, 48 were female and 56 male. 23 (22%) had stage II disease, 12 of these with bulky disease, 45 (43%) stage III and 36 (35%) with stage IV. 65 (63%) had IPS 0-2 and 39 (37%) had IPS >2. The institutional 5-year EFS for ABVD patients regardless of IPS was 66%. For those with IPS 0-2 the institutional EFS was 71% compared with 74% reported by the IPS project. The institutional 5 year EFS for patients treated with ABVD with IPS >2 was 55%, compared with 55% reported by the IPS project. With a median of 5 year follow up (6-94 months) the projected EFS for RABVD is 87% which is significantly better than institutional results with ABVD (p=0.0036). Improvement in EFS was observed with RABVD in patients with IPS 0-2 (EFS 89% vs. 71%, p=0.0248); and those with IPS >2 (80% vs. 55%; p=0.0532). In conclusion, this long term follow up data confirms the superiority of RABVD to ABVD in patients with advanced stage classical HL in all risk groups. This data serves as the rationale for a multicenter randomized trial comparing ABVD with RABVD in newly diagnosed patients with classical HL with stage III and IV and IPS >2. The study is currently enrolling patients. Disclosures Off Label Use: Rituximab in Hodgkin lymphoma. Younes:Genentech: Honoraria, Research Funding.

Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Long-Term Efficacy from the Phase 1b Keynote-013 Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1108-1108 ◽  
Author(s):  
Philippe Armand ◽  
Margaret A. Shipp ◽  
Vincent Ribrag ◽  
Jean-Marie Michot ◽  
Pier Luigi Zinzani ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Brentuximab Vedotin ◽  
Classical Hodgkin Lymphoma ◽  
Advisory Committees ◽  
End Points ◽  
Phase 1B

Abstract Background: Patients with classical Hodgkin lymphoma (cHL) who progress after brentuximab vedotin (BV) have a poor prognosis. cHL frequently harbors genetic alterations at the 9p24.1 locus, resulting in the overexpression of the PD-L1 and PD-L2 immune checkpoint ligands. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between the PD-1 receptor and PD-L1/PD-L2, and can restore antitumor immune activity in several different tumors. Based on its likely genetically driven dependence on PD-1, cHL was included as an independent expansion cohort in the KEYNOTE-013 study (NCT01953692), a multicenter, multicohort phase 1b trial of pembrolizumab in patients with hematologic malignancies. Updated results from this cohort, including long-term efficacy, are presented. Methods: Key eligibility criteria for the cHL cohort of KEYNOTE-013 included relapse after or ineligibility for autologous stem cell transplantation (ASCT), and relapse after or refractory to BV treatment. Pembrolizumab was administered intravenously at a dose of 10 mg/kg every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Response was assessed at week 12 and every 8 weeks thereafter according to the International Harmonization Project 2007 criteria. The primary end points were safety and complete remission (CR) rate (CRR); secondary end points included overall response rate (ORR) and duration of response (DOR). Patients who achieved a CR could opt to stop treatment after 24 weeks provided that they received at least 2 doses after CR. This report includes CRR, ORR, and DOR by blinded independent central review (BICR). Results: At the time of data cutoff on June 3, 2016, 31 patients were enrolled, and all were evaluable for analysis. Median follow-up duration was 24.9 months (range, 7.0-29.7 months). The median number of prior lines of therapy was 5 (range, 2-15), 74% of patients had failed prior ASCT, and by design 100% had failed prior BV. Per investigator review, ORR was 65%, and CRR was 19%. Per BICR, ORR was 58% (18/31), with 6 patients (19%) achieving CR and 12 (39%) partial remission; 7 patients (23%) had stable disease as their best response. Median DOR was not reached, with a range of 0.0+ to 21.4+ months (95% CI, 3.7 months to not reached) (Figure). An analysis with hierarchical mutually exclusive categories of refractory disease (RD; defined as no response to ≥1 prior line of therapy) or relapse after ≥3 prior lines of therapy (Re ≥3) was conducted. Per BICR, the ORR was 56% in RD (n = 27 patients) and 75% in Re ≥3 (n = 4). As of the data cutoff date, 3 patients (10%) remained on treatment, 5 (16%) completed 2 years of treatment, and 23 (74%) discontinued treatment: 3 (10%) for toxicity, 14 (45%) for progressive disease, 3 (10%) per physician decision (all ultimately underwent allogeneic SCT), 1 in CR (underwent allogeneic SCT), 1 for clinical progression, and 1 who withdrew consent. Per BICR, median progression-free survival (PFS) was 11.4 months; 6-month and 12-month PFS rates were 66% and 48%, respectively. Median overall survival (OS) was not reached; 6-month and 12-month OS rates were 100% and 87%, respectively. Conclusions: With nearly 2.5 years of median follow-up, the present results demonstrate that a subset of heavily pretreated patients who failed BV therapy can achieve a long-term response with single-agent pembrolizumab, without consolidative therapy. PD-1 blockade may offer a new treatment paradigm for patients with relapsed/refractory cHL, supporting the hypothesis that this tumor has a genetic dependence on the PD-1 pathway. Figure Figure. Disclosures Armand: BMS: Consultancy, Research Funding; Sequenta: Research Funding; Roche: Research Funding; Infinity: Consultancy; Merck & Co., Inc.: Consultancy, Research Funding; Sigma Tau: Research Funding; Tensha: Research Funding; Otsuka: Research Funding. Shipp:Cell Signaling: Honoraria; Bayer: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Merck, Gilead, Takeda: Other: Scientific Advisory Board. Ribrag:Incyte: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; ArgenX: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; Esai: Membership on an entity's Board of Directors or advisory committees. Michot:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Zinzani:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Sandoz: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees. Kuruvilla:Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Merck: Honoraria; Roche Canada: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Honoraria. Zhu:Merck: Employment. Ricart:Merck & Co.: Employment; Pfizer: Equity Ownership. Balakumaran:Merck & Co.: Employment, Other: stock, stock options. Moskowitz:Pharmacyclics: Research Funding; Merck: Consultancy, Research Funding; Genentech: Consultancy; Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy.

scholarly journals Five-year results of the BEGEV salvage regimen in relapsed/refractory classical Hodgkin lymphoma

2020 ◽  
Vol 4 (1) ◽  
pp. 136-140 ◽  
Author(s):  
Armando Santoro ◽  
Rita Mazza ◽  
Alessandro Pulsoni ◽  
Alessandro Re ◽  
Maurizio Bonfichi ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Progression Free Survival ◽  
Classical Hodgkin Lymphoma ◽  
Salvage Regimen ◽  
Intention To Treat ◽  
Significant Difference ◽  
Excellent Safety Profile ◽  
Further Development

Abstract The complete remission (CR) rate achieved with induction chemotherapy prior to autologous stem cell transplantation (ASCT) represents the strongest prognostic factor in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). By inducing a CR rate of 75%, the bendamustine, gemcitabine, vinorelbine (BEGEV) regimen represents an optimal chemotherapy regimen prior to ASCT. Presented here are the 5-year results of BEGEV followed by ASCT in R/R cHL. With a median follow-up of 5 years, progression-free survival (PFS) and overall survival (OS) for the whole series (n = 59) were 59% and 78%, respectively. ASCT was performed in 43 of 49 responding patients (73% by intention to treat [ITT]; 88% by response to BEGEV) and resulted in 33 with continuous CR (56% by ITT; 77% of transplanted patients), 7 with disease relapse, and 3 with nonrelapse mortality. For patients who received transplants, the 5-year PFS and OS were 77% and 91%, respectively, with no significant difference between relapsed and refractory patients. No patient experienced secondary leukemia or myelodysplasia. In summary, the long-term efficacy data, the benefits for both relapsed and refractory patients, and the excellent safety profile provide a strong rationale for further development of the BEGEV regimen. This trial was registered at EudraCT as #2010-022169-91 and at www.clinicaltrials.gov as #NCT01884441.

scholarly journals KEYNOTE-013 4-year follow-up of pembrolizumab in classical Hodgkin lymphoma after brentuximab vedotin failure

2020 ◽  
Vol 4 (12) ◽  
pp. 2617-2622 ◽  
Author(s):  
Philippe Armand ◽  
John Kuruvilla ◽  
Jean-Marie Michot ◽  
Vincent Ribrag ◽  
Pier Luigi Zinzani ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Brentuximab Vedotin ◽  
Long Term Results ◽  
Classical Hodgkin Lymphoma ◽  
Duration Of Response

Abstract The KEYNOTE-013 study was conducted to evaluate pembrolizumab monotherapy in hematologic malignancies; classical Hodgkin lymphoma (cHL) was an independent expansion cohort. We present long-term results based on &gt;4 years of median follow-up for the cHL cohort. The trial enrolled cHL patients who experienced relapse after, were ineligible for, or declined autologous stem cell transplantation and experienced progression with or did not respond to brentuximab vedotin. Patients received IV pembrolizumab 10 mg/kg every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points were safety and complete response (CR) rate by central review. Enrolled patients (N = 31) had received a median of 5 therapies (range, 2 to 15). After a median follow-up of 52.8 months (range, 7.0 to 57.6 months), CR rate was 19%, and median duration of response (DOR) was not reached; 24-month and 36-month DOR rates were both 50% by the Kaplan-Meier method. Median overall survival was not reached; 36-month overall survival was 81%. Six patients (19%) experienced grade 3 treatment-related adverse events (AEs); there were no grade 4 or 5 treatment-related AEs. With long-term follow-up among a heavily pretreated cohort, pembrolizumab had a favorable safety profile; some patients maintained long-term response with pembrolizumab years after end of treatment. This trial was registered at www.clinicaltrials.gov as #NCT01953692.

scholarly journals Cardiovascular Disease Is the Main Cause of Long-Term Excess Mortality After Ischemic Stroke in Young Adults

Hypertension ◽  
2015 ◽  
Vol 65 (3) ◽  
pp. 670-675 ◽  
Author(s):  
Loes C.A. Rutten-Jacobs ◽  
Renate M. Arntz ◽  
Noortje A.M. Maaijwee ◽  
Hennie C. Schoonderwaldt ◽  
Lucille D. Dorresteijn ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Young Adults ◽  
Ischemic Stroke ◽  
Excess Mortality ◽  
Stroke In Young Adults ◽  
Stroke In Young

Antipsychotic medication and long-term mortality risk in patients with schizophrenia; a systematic review and meta-analysis

2017 ◽  
Vol 47 (13) ◽  
pp. 2217-2228 ◽  
Author(s):  
J. Vermeulen ◽  
G. van Rooijen ◽  
P. Doedens ◽  
E. Numminen ◽  
M. van Tricht ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Mortality Risk ◽  
Causes Of Death ◽  
Meta Analysis ◽  
Mortality Rates ◽  
Cumulative Exposure ◽  
The Relationship ◽  
Long Term Mortality

Patients with schizophrenia have a higher mortality risk than patients suffering from any other psychiatric disorder. Previous research is inconclusive regarding the association of antipsychotic treatment with long-term mortality risk. To this aim, we systematically reviewed the literature and performed a meta-analysis on the relationship between long-term mortality and exposure to antipsychotic medication in patients with schizophrenia. The objectives were to (i) determine long-term mortality rates in patients with schizophrenia using any antipsychotic medication; (ii) compare these with mortality rates of patients using no antipsychotics; (iii) explore the relationship between cumulative exposure and mortality; and (iv) assess causes of death. We systematically searched the EMBASE, MEDLINE and PsycINFO databases for studies that reported on mortality and antipsychotic medication and that included adults with schizophrenia using a follow-up design of more than 1 year. A total of 20 studies fulfilled our inclusion criteria. These studies reported 23,353 deaths during 821,347 patient years in 133,929 unique patients. Mortality rates varied widely per study. Meta-analysis on a subgroup of four studies showed a consistent trend of an increased long-term mortality risk in schizophrenia patients who did not use antipsychotic medication during follow-up. We found a pooled risk ratio of 0.57 (LL:0.46 UL:0.76 p value <0.001) favouring any exposure to antipsychotics. Statiscal heterogeneity was found to be high (Q = 39.31, I2 = 92.37%, p value < 0.001). Reasons for the increased risk of death for patients with schizophrenia without antipsychotic medication require further research. Prospective validation studies, uniform measures of antipsychotic exposure and classified causes of death are commendable.

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