Secondary Malignancies in CML Patients – Data From the German CML Study IV

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3746-3746 ◽  
Author(s):  
Manuel Barreto Miranda ◽  
Michael Lauseker ◽  
Ulrike Proetel ◽  
Annette Schreiber ◽  
Benjamin Hanfstein ◽  
...  
Keyword(s):  
General Population ◽  
Confidence Interval ◽  
Incidence Rate ◽  
Interferon Alpha ◽  
Research Funding ◽  
Incidence Rates ◽  
Primary Cancer ◽  
Secondary Malignancies

Abstract Abstract 3746 Introduction: The increase of overall survival in chronic myeloid leukemia (CML) requires closer long-term observation in the face of a potential carcinogenicity of tyrosine kinase inhibitors (TKIs). Preclinical studies with imatinib in rats showed neoplastic changes in kidneys, urinary bladder, urethra, preputial and clitoral glands, small intestine, parathyroid glands, adrenal glands, and nonglandular stomach. Two epidemiologic studies on patients with chronic myeloproliferative neoplasms (CMPN) and CML (Frederiksen H et al., Blood 2011; Rebora P et al., Am J Epidemiol 2010) found an increased risk of secondary malignancies compared with the general population independent of treatment. In contrast, in a recent analysis of patients with CML and CMPN treated with TKI (Verma D et al., Blood 2011) a decreased risk of secondary malignancies was reported. Aims: To further elucidate the risk of TKI treated CML patients for the development of secondary malignancies we analysed data of the CML study IV, a randomized 5-arm trial (imatinib 400 mg vs. imatinib 800 mg vs. imatinib 400 mg in combination with interferon alpha vs. imatinib 400 mg in combination with AraC vs. imatinib 400 mg after interferon failure). Patients and methods: From February 2002 to April 2012, 1551 CML patients in chronic phase were randomized, 1525 were evaluable. Inclusion criteria allowed the history of primary cancer if the disease was in stable remission. Forty-nine malignancies were reported in 43 patients before the diagnosis of CML. If relapses occurred within 5 years after diagnosis of primary cancer they were not considered for further analysis. Median follow-up was 67.5 months. Age-standardized incidence rates were calculated from the age-specific rates using the European standard population (1976). Results: In total, 67 secondary malignancies in 64 patients were found in CML patients treated with TKI (n=61) and interferon alpha only (n=3). Twelve of these patients developed neoplasms after diagnosis of a primary cancer before diagnosis of CML, 5 patients with metastases or recurrence of the first malignancy (range of diagnosis 5–19 years after primary cancer). Median time to secondary malignancy was 2.5 years (range 0.1–8.3 years). The types of neoplasms were: prostate (n=9), colorectal (n=6), lung (n=6), non Hodgkin's lymphoma (NHL; n=7), malignant melanoma (n=5), skin tumors (basalioma n=4 and squamous cell carcinoma n=1), breast (n=5), pancreas (n=4), kidney (n=4), chronic lymphocytic leukemia (n=3), head and neck (n=2), biliary (n=2), sarcoma (n=2), and esophagus, stomach, liver, vulva, uterus, brain, cancer of unknown origin (each n=1). With these numbers the age-standardized incidence rates of secondary malignancies in CML patients were calculated: 534 cases per 100,000 for men (confidence interval [350;718]), and 582 for women (confidence interval [349;817]). The incidence rates of the general population in Germany were 450 and 350 cases, respectively (“Krebs in Deutschland 2007/2008”, 8th ed., Robert Koch Institute, 2012). The incidence rate of NHLs was higher for CML patients than for the general population but this is not significant. Conclusions: In our cohort, the incidence rate of secondary neoplasms in CML patients was slightly increased compared to the general population. The most common secondary malignancies in CML patients under treatment were cancers of the skin, prostate, colon, lung and NHL. Since the occurrence of secondary neoplasia increases over time, long-term follow-up of CML patients is warranted. Disclosures: Müller: Novartis, BMS: Consultancy, Honoraria, Research Funding. Hochhaus:Novartis, BMS, MSD, Ariad, Pfizer: Consultancy Other, Honoraria, Research Funding. Hehlmann:Novartis: Research Funding.

Thirty-Five Year Follow-up Analysis of Follicular Lymphoma Patients Treated through the Nebraska Lymphoma Study Group: Prognostic Factor Analysis and Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Amulya Yellala ◽  
Elizabeth R. Lyden ◽  
Heather Nutsch ◽  
Avyakta Kallam ◽  
Kai Fu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Treatment Regimen ◽  
Research Funding ◽  
Study Group ◽  
Secondary Malignancies ◽  
Lymphoma Study Group

Background Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL) and most common of the clinically indolent NHLs. Although often considered an incurable disease, overall survival has increased significantly with refinement in diagnostic techniques and the addition of rituximab. The course of FL is quite variable and presence of symptoms, organ dysfunction, cytopenias, aggressiveness of tumor are all taken into consideration when deciding individual treatment. In this study, we evaluated a large patient cohort with FL treated over a 35 year period for progression free survival (PFS), overall survival (OS) based on FLIPI score, tumor grade, and treatment regimen and also looked at causes of late failures. Methods We evaluated 1037 patients (pts) from the Nebraska Lymphoma Study Group that were diagnosed with FL between the years of 1983-2020. Descriptive statistics were stratified according to age, histological subtype, treatment regimen, FLIPI category, presence and type of secondary malignancy. PFS was calculated from the time of diagnosis to progression or death and OS was the time from diagnosis to death from any cause. PFS and OS were plotted as Kaplan-Meier curves with statistically significant p<0.05. Results The median age at diagnosis and treatment was 61 years (yrs, range 17-91). A total of 9.1% were characterized as FLIPI high risk, 37.8% intermediate risk, and 33.6% low risk, 19.5% unavailable. Among the histological grade, 23.1% had FL- grade 1, 30.2% FL-2, 27.3% FL-3A, 2.5 % FL-3B and 16.9 % Composite Lymphoma. Anthracycline + rituximab was given in 24.5% of pts, whereas 43.8% of pts received an anthracycline based regimen without rituximab, 9.8% received rituximab without an anthracycline and 10.6% received neither of these agents. 6.75% (70 pts) were later found to have secondary malignancies of which 11 pts had myelodysplastic syndrome, 10 pts had acute leukemia and 9 pts had lung cancer. With a median follow up of 9.2 yrs and a maximum of 36 yrs, 29.7% (308 pts) had not relapsed. The median PFS across all groups was 4.6 yrs (Fig 1) and OS was 12.1 yrs. Median OS was significantly longer in patients that received rituximab at 16.1 yrs as compared to patients that did not receive rituximab at 9.89 yrs (Fig 2). PFS was 8.6 yrs, 3.6 yrs and 2.1 yrs and OS was 15.1 yrs, 11.7 yrs and 4.9 yrs in FLIPI low, intermediate and high risk groups respectively (p=<0.001) (Fig 3), suggesting that survival was influenced by FLIPI score. Median PFS in FL-3B and FL-3A was 9.2 yrs and 5.2 yrs respectively which is longer than 4.7 yrs and 4.2 yrs for FL-1 and FL-2 (p=0.24). OS in FL-3A and FL-3B subgroups was 10.8 yrs while it was 11.6 yrs and 14.3 yrs in FL-2 and FL-1 (P=0.081). PFS is significantly longer at 10.6 yrs in pts treated with both anthracycline and rituximab containing regimen as compared to 5.3 yrs in pts treated with rituximab alone and 3.05 yrs in pts that had only anthracycline based regimen (p=<0.001) (Fig 4). The median OS also was significantly higher in the combination regimen group at 18.8 yrs as compared to 11.3 yrs in rituximab only group and 9 yrs in anthracycline based regimen group (p=<0.001). When pts with FL-3A and FL-3B were grouped together and stratified according to treatment regimen, the group that received anthracycline and rituximab combination has highest PFS and OS at 13.3 yrs and 18.8 yrs (p<0.001). when pts with FL-3A were analyzed separately and stratified by treatment regimen, the results of PFS and OS were similar and statistically significant. However, of the 24 pts in FL-3B group, analysis revealed that PFS and OS was longer in anthracycline based regimen only group, however results were not statistically significant. Among the pts that relapsed/died after 10 years (n=190), the cause of death was relapsed lymphoma in 13.7%, unknown in 55.8%, secondary malignancies in 4.2%, treatment related in 2.6% and not related to disease in 23.7%. A total of 278 pts survived > 10 yrs, and of these pts, 119 (30%) had not relapsed at the last follow up. Conclusion The addition of rituximab to standard anthracycline based chemotherapy has resulted in significant improvements in the PFS and OS rates of FL. These results also support the prognostic value of the FLIPI in patients treated in the rituximab era. Late relapses after 10 yrs from disease can occur, but 11.5% of patients had not relapsed with long term follow up. Secondary malignancies are also an important consideration in the long term survivors. Disclosures Lunning: Acrotech: Consultancy; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Verastem: Consultancy, Honoraria; ADC Therapeutics: Consultancy. Armitage:Trovagene/Cardiff Oncology: Membership on an entity's Board of Directors or advisory committees; Samus Therapeutics: Consultancy; Ascentage: Consultancy. Vose:Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Seattle Genetics: Research Funding; Allogene: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Wugen: Honoraria; Novartis: Research Funding; Celgene: Honoraria; Incyte: Research Funding; Roche/Genetech: Consultancy, Honoraria, Other; Verastem: Consultancy, Honoraria; Miltenyi Biotec: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Epizyme: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria.

Risk of Second Primary Malignancies in Patients with AL Amyloidosis Treated with Lenalidomide

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1873-1873
Author(s):  
Vaishali Sanchorawala ◽  
Anthony C Shelton ◽  
Gheorghe Doros ◽  
David C Seldin
Keyword(s):  
General Population ◽  
Incidence Rate ◽  
Research Funding ◽  
Hematologic Malignancy ◽  
Alkylating Agents ◽  
Plasma Cell Dyscrasia ◽  
Second Primary ◽  
Al Amyloidosis ◽  
Second Primary Malignancies

Abstract Abstract 1873 An increase in second primary malignancies (SPM) has been reported in patients with myeloma treated with lenalidomide, particularly in association with melphalan. To determine the rate of second primary malignancies in AL amyloidosis patients treated with lenalidomide, we reviewed data on 82 patients treated on clinical trials at Boston Medical Center from 2004–2011. Data from lenalidomide and dexamethasone treatment in AL amyloidosis (ClinicalTrials.gov: NCT00091260) were analyzed in a post-hoc fashion for the incidence rate for SPM. The median age of these 82 patients was 62 years (range, 40–82); and 52 (63%) were male. There were 62 patients (76%) with lambda clonal plasma cell dyscrasia, and 43 (52%) had cardiac involvement by the consensus criteria from the Xth International Amyloidosis Symposium. Median duration for lenalidomide treatment was 9 cycles (range, 1–69); and 16 (20%) received lenalidomide for > 24 months. Of the 82 patients, 78 (95%) patients had prior therapies and 77 (94%) had prior alkylating agents based treatment. The median follow-up of the 82 patients was 28 months (range, 3–92). One patient, a smoker, treated with lenalidomide for 24 months, developed metastatic lung cancer. Additionally, there were 5 non-melanoma skin cancers. There was no case of hematologic malignancy or B-cell lymphoproliferative disorder in this group. This corresponds to an incidence rate of 0.44 per 100 patient-years for invasive cancer. The annual incidence of invasive cancers is 2.1 per 100 patient-years for the general population in the US. In conclusion, lenalidomide based treatment in AL amyloidosis did not appear to increase the incidence rate of SPM compared to incidence rate for the invasive cancers in general population. Longer prospective follow-up may be needed in a larger patient population to better define the risk. Disclosures: Sanchorawala: Celgene Corporation: Research Funding. Off Label Use: Use of lenalidomide in the treatment of AL amyloidosis. Seldin:Celgene Corporation: Research Funding.

scholarly journals Increased risk of hyperlipidemia in patients with anxiety disorders: A population-based study

2020 ◽  
Author(s):  
I-Chia Chien ◽  
Ching-Heng Lin
Keyword(s):  
General Population ◽  
Confidence Interval ◽  
Anxiety Disorders ◽  
Incidence Rate ◽  
Prevalence Rate ◽  
Female Gender ◽  
Incidence Rates ◽  
Secondary Diagnosis ◽  
Increased Risk ◽  
Incident Cases

Abstract Objective This study examined the prevalence and incidence of hyperlipidemia among patients with anxiety disorders in Taiwan. Methods We used a large dataset containing random samples, and more than 766,000 subjects who were aged 18 years or older in 2005 were identified. Subjects who had more than one primary or secondary diagnosis of anxiety disorders were identified. Individuals who had a primary or secondary diagnosis of hyperlipidemia or medication treatment for hyperlipidemia were also identified. The prevalence rate of hyperlipidemia in patients with anxiety disorders with that of the general population in 2005 was compared. We then followed this cohort to monitor incident cases of hyperlipidemia in anxiety patients, and assessed whether a difference existed from the general population during the period 2006–2010. Results A higher prevalence rate of hyperlipidemia in patients with anxiety disorders was observed as compared with the general population (21.3% vs. 7.6%, odds ratio 2.14; 95% confidence interval, 2.07–2.22) in 2005. Additionally, a higher average annual incidence rate of hyperlipidemia in patients with anxiety disorders was also found as compared with the general population (5.49% vs. 2.50%, risk ratio 1.64; 95% confidence interval, 1.58–1.70) from 2006 to 2010. Conclusions Patients with anxiety disorders had higher prevalence and incidence rates of hyperlipidemia than the general population. Risk factors that were found to be associated with the higher incidence rate of hyperlipidemia among anxiety patients included a greater age, the female gender, and the presence of diabetes and hypertension.

scholarly journals Incidence and Risk Factors for Invasive Pneumococcal Disease and Community-acquired Pneumonia in Human Immunodeficiency Virus–Infected Individuals in a High-income Setting

2019 ◽  
Vol 71 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Hannah M Garcia Garrido ◽  
Anne M R Mak ◽  
Ferdinand W N M Wit ◽  
Gino W M Wong ◽  
Mirjam J Knol ◽  
...  
Keyword(s):  
Risk Factors ◽  
Human Immunodeficiency Virus ◽  
General Population ◽  
Confidence Interval ◽  
Incidence Rate ◽  
Pneumococcal Disease ◽  
Incidence Rates ◽  
Community Acquired Pneumonia ◽  
Cd4 Counts ◽  
Immunodeficiency Virus

Abstract Background Although people living with human immunodeficiency virus (PLWH) are at increased risk of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP), it is unclear whether this remains the case in the setting of early initiation of combination antiretroviral therapy (cART), at high CD4 cell counts. This is important, as pneumococcal vaccination coverage in PLWH is low in Europe and the United States, despite longstanding international recommendations. Methods We identified all CAP and IPD cases between 2008 and 2017 in a cohort of PLWH in a Dutch HIV referral center. We calculated incidence rates stratified by CD4 count and cART status and conducted a case-control study to identify risk factors for CAP in PLWH receiving cART. Results Incidence rates of IPD and CAP in PLWH were 111 and 1529 per 100 000 patient-years of follow-up (PYFU). Although IPD and CAP occurred more frequently in patients with CD4 counts <500 cells/μL (incidence rate ratio [IRR], 6.1 [95% confidence interval, 2.2–17] and IRR, 2.4 [95% confidence interval, 1.9–3.0]), the incidence rate in patients with CD4 counts >500 cells/μL remained higher compared with the general population (946 vs 188 per 100 000 PYFU). All IPD isolates were vaccine serotypes. Risk factors for CAP were older age, CD4 counts <500 cells/μL, smoking, drug use, and chronic obstructive pulmonary disease. Conclusions The incidence of IPD and CAP among PLWH remains higher compared with the general population, even in those who are virally suppressed and have high CD4 counts. With all serotyped IPD isolates covered by pneumococcal vaccines, our study provides additional argumentation against the poor current adherence to international recommendations to vaccinate PLWH.

Contemporary Estimates of the Incidence of Venous Thromboembolism: A Population-Based Cohort Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1143-1143
Author(s):  
Vicky Tagalakis ◽  
Valerie Patenaude ◽  
Susan R. Kahn ◽  
Samy Suissa
Keyword(s):  
Venous Thromboembolism ◽  
General Population ◽  
Incidence Rate ◽  
Conflicts Of Interest ◽  
Public Health Problem ◽  
Incidence Rates ◽  
Future Research ◽  
Public Healthcare ◽  
Source Population

Abstract Abstract 1143 Background: Venous thromboembolism (VTE) is a growing public health problem due largely to the aging population and the increasing prevalence of known risk factors such as surgery and cancer-related treatments. As a result, the true burden of VTE is not fully known and more contemporary estimates of incidence are needed. Objectives: We estimated the incidence of a first VTE event in a general population. Methods: This retrospective, observational study used the linked administrative healthcare databases of the province of Québec, Canada, including the province-wide hospitalization database (MED-ÉCHO) and the healthcare services database of RAMQ which oversees all physician reimbursement claims for services provided to Québec residents. From a source population of all RAMQ beneficiaries with a physician visit or a hospitalization associated with an ICD-9-CM or ICD-10-CA diagnosis code for deep vein thrombosis (DVT) or pulmonary embolism (PE) recorded between January 1, 2000 and December 31, 2009 and without a DVT or PE code prior to January 1, 2000, we identified a cohort of Québec residents with definite incident VTE and a cohort with definite or probable incident VTE. We used a priori determined diagnostic algorithms using RAMQ and MED-ÉCHO data to identify definite and probable cases of VTE. Subjects were followed forward in time from first-time VTE occurrence until the earliest of either death or end of study period (December 31, 2009). Incidence rates of first VTE, DVT alone, and PE with or without DVT were calculated by dividing the number of new cases by the total person-years at risk in the population of Québec residents eligible for RAMQ between 2000 and 2009. Age-specific incidence rates and associated 95% confidence intervals (CI) were calculated using achieved age during follow-up, and as a result patients contributed person-time in different age categories while aging during follow-up. Crude and age-adjusted incidence rate ratios (IRR) were reported comparing rates among women and men. Results: From the 245 452 Québec residents between 2000 and 2009 with at least 1 VTE diagnosis in RAMQ or MED-ÉCHO (source population), we identified 67 410 cases with definite VTE and 35 123 cases with probable VTE. The incidence rate of definite VTE was 0.91 per 1000 person-years (95% CI: 0.90–0.91). For DVT alone, the incidence was 0.53 per 1000 person-years (95% CI: 0.52–0.52) and for PE with or without DVT it was 0.38 per 1000 person-years (95% CI: 0.38–0.38). The incidence rates increased with age, and rates in patients 70 years of age and older were more than 4 times higher than rates in patients who were 40–69 years of age (Table 1). The VTE incidence rate was 0.99 per 1000 person-years (95% CI: 0.98–1.00) in women as compared to 0.82 per 1000 person-years (95% CI: 0.81–0.83) in men. The IRR was 1.19 (95% CI: 1.17–1.22) but this sex difference was no longer seen when adjusted for age (IRR 0.98; 95% CI: 0.96–1.01). The corresponding VTE, DVT alone, and PE incidence rates per 1000 person-years for definite or probable VTE were 1.24 (95% CI: 1.23–1.24), 0.79 (95% CI: 0.78–0.79), and 0.45 (95% CI: 0.45–0.46), respectively. Conclusion: Our study provides real-world contemporary estimates of VTE incidence. The risk in the general population is about 0.9 to 1.2 per 1000 person-years and is highest in the elderly. These data may help inform public healthcare planning and future research. Disclosures: No relevant conflicts of interest to declare.

Sustained Overall Survival Benefit with Lenalidomide Plus Dexamethasone Versus No Treatment in Patients with Smoldering Myeloma at High Risk of Progression to Myeloma: Long Term Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3308-3308 ◽  
Author(s):  
Maria-Victoria Mateos ◽  
Miguel-T Hernandez ◽  
Pilar Giraldo ◽  
Javier De La Rubia ◽  
Felipe De Arriba ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Confidence Interval ◽  
Board Of Directors ◽  
Early Treatment ◽  
Survival Benefit ◽  
Research Funding ◽  
Advisory Committees

Abstract Background: For patients with smoldering multiple myeloma (SMM), the standard of care is observation. However, high-risk patients may benefit from early intervention. Methods: In this phase 3 trial, 119 patients with high-risk SMM were randomized to treatment or observation. The high risk populationwas defined by the presence of both PC_ 10% and MC_ 3g/dl or ifonly one criterion was present, patients must have a proportionof aPC within the total PCBM compartment by immunophenotypingof 95% plus immunoparesis. Patients in the treatment group received nine 4-week induction cycles (lenalidomide at a dose of 25 mg per day on days 1 to 21, plus dexamethasone at a dose of 20 mg per day on days 1 to 4 and days 12 to 15), followed by maintenance (lenalidomide at a dose of 10 mg per day on days 1 to 21 of each 28-day cycle) up to 2 years. The primary end point was time to progression (TTP) to myeloma. Secondary end points were overall survival (OS), response rate and safety. Results: After a median follow-up of 75 months (range: 57-100), there was a 57% reduction in the risk of death for the early treatment with lenalidomide-dexamethasone versus not treatment (hazard ratio, 0.43; 95% confidence interval, 0.2 to 0.9; P=0.02). Median overall survival has not been reached in either group, but 86% and 62% of patients are alive at 6 years in the early treatment and observation arms, respectively (Figure 1). The benefit in TTP is also highly sustained (hazard ratio: 0.24 (95% confidence interval, 0.14 to 0.41; P<0.0001). Progression to MM occurred in 53 out of the 62 patients (86%) in the abstention arm while only 22 out of 57 patients (38%) in the len-dex arm. At the time of progression patients received optimized treatments: bortezomib-based combinations were administered to thirteen out of 22 patients (59%) in the len-dex arm and to 23 out of 53 patients (43%) in the observation arm; lenalidomide-based combinations to 3 out of 22 patients (14%) in the experimental and to 8 out of 53 patients (15%) in the control arm; two out of 22 patients in the len-dex arm (9%) received bortezomib plus immunomodulatory agents whilst 16 out of 53 patients (30%) in the observation group received this combination; four out of 22 patients (18%) and six out of 53 patients (11%) in the len-dex and observation groups, respectively, were treated with chemotherapy; four patients (18%) in the experimental arm and 15 (28%) in the observation groups received an ASCT. Most patients responded to rescue therapies in both arms, resulting in overall response rates of 78% (17/22) and 86% (45/53) in the experimental and control arm, respectively. We compared survival from start of subsequent therapy in the patients population who progressed to active disease; the outcome was similar in both arms: at 6 years, 62% (16/22) of the patients in the len-dex arm remain alive and 49% (31/53) in the observation arm (P=0.50; Fig. 2C). The survival benefit observed was independent of the classification model used for defining high risk SMM ( Mayo Clinic and Spanish model) Conclusion: This long term follow-up analysis confirms that early treatment with lenalidomide-dexamethasone for high-risk SMM translates into a significant benefit in TTP but also in a sustained significant prolongation of the OS. The early exposure to lenalidomide-dexamethasone does not induce more resistant relapses. Figure 1 Figure 1. Disclosures Mateos: Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria. De La Rubia:Amgen, Bristol Myers, Celgene, Janssen: Consultancy. Paiva:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; EngMab: Research Funding; Amgen: Honoraria; Binding Site: Research Funding. Oriol:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Prostate Brachytherapy and Second Primary Cancer Risk: A Competitive Risk Analysis

2011 ◽  
Vol 29 (34) ◽  
pp. 4510-4515 ◽  
Author(s):  
Karel A. Hinnen ◽  
Michael Schaapveld ◽  
Marco van Vulpen ◽  
Jan. J. Battermann ◽  
Henk van der Poel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Rectal Cancer ◽  
General Population ◽  
Lead Time ◽  
Incidence Rates ◽  
Second Primary ◽  
Prostate Brachytherapy ◽  
Primary Cancer ◽  
Second Primary Cancer

Purpose To assess the risk of second primary cancer (SPC) after [125I]iodine prostate cancer brachytherapy compared with prostatectomy and the general population. Patients and Methods In a cohort consisting of 1,888 patients with prostate cancer who received monotherapy with brachytherapy (n = 1,187; 63%) or prostatectomy (n = 701; 37%), SPC incidences were retrieved by linkage with the Dutch Cancer Registry. Standardized incidence rates (SIRs) and absolute excess risks (AERs) were calculated for comparison. Results A total of 223 patients were diagnosed with SPC, 136 (11%) after brachytherapy and 87 (12%) after prostatectomy, with a median follow-up of 7.5 years. The SIR for all malignancies, bladder cancer, and rectal cancer were 0.94 (95% CI, 0.78 to 1.12), 1.69 (95% CI, 0.98 to 2.70), and 0.90 (95% CI, 0.41 to 1.72) for brachytherapy and 1.04 (95% CI, 0.83 to 2.28), 1.82 (95% CI, 0.87 to 3.35), and 1.50 (95% CI, 0.68 to 2.85) for prostatectomy, respectively. Bladder SPC risk was significantly increased after brachytherapy for patients age 60 years or younger (SIR, 5.84; 95% CI, 2.14 to 12.71; AER, 24.03) and in the first 4 years of follow-up (SIR, 2.14; 95% CI, 1.03 to 3.94; AER, 12.24). Adjusted for age, the hazard ratio (brachytherapy v prostatectomy) for all SPCs combined was 0.87 (95% CI, 0.64 to 1.18). Conclusion Overall, we found no difference in SPC incidence between patients with prostate cancer treated with prostatectomy or brachytherapy. Furthermore, no increased tumor incidence was found compared with the general population. We observed a higher than expected incidence of bladder SPC after brachytherapy in the first 4 years of follow-up, probably resulting from lead time or screening bias. Because of power limitations, a small increased SPC risk cannot be formally excluded.

scholarly journals Autoimmune Hemolytic Anemia: A Disease of the Elderly and the Very Elderly with Increased Mortality and Increased Rates of Hospitalization for Thrombosis and Infection

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-41
Author(s):  
Julien Maquet ◽  
Margaux Lafaurie ◽  
Agnès Sommet ◽  
Maryse Lapeyre-Mestre ◽  
Guillaume Moulis
Keyword(s):  
General Population ◽  
Cumulative Incidence ◽  
Research Funding ◽  
The Elderly ◽  
Evans Syndrome ◽  
Very Elderly ◽  
Risk Of Death ◽  
Incidence Of Hospitalization

Introduction Autoimmune hemolytic anemia (AIHA) is a rare disease characterized by the destruction of red blood cells by warm or cold autoantibodies. Epidemiological data are lacking about AIHA incidence, the prevalence of associated disorders and the risk of death, thrombosis and infection as compared with the general population. This study was designed to answer these questions. Methods Patients were selected from the AHEAD cohort. This cohort is built in the French national health database (named Système national des données de santé, SNDS) linking sociodemographics, out-hospital and hospital data for the entire French population (67 million inhabitants). The AHEAD cohort is the cohort of all incident AIHA in France. Patients were selected between 2012-2017. The date of AIHA diagnosis was defined by the first hospital discharge diagnosis or the first long-term disease (recorded by general practitioners) of AIHA occurring after a prior observation period in the SNDS of at least two years. Patients were identified using the D59.1 code of the international classification of diseases, version 10 (positive predictive value: 90.0%). The incidence of AIHA was calculated in the whole French population, by age, sex and calendar months. Causes of secondary AIHA and Evans syndrome were searched in the year before the diagnosis of AIHA using long-term disease and hospital discharge diagnoses. Each patient was matched to five controls on age and sex from the general population. The follow-up ended on December 31, 2018. One- and five-year cumulative incidences of death, hospitalization for thrombosis and for infection were assessed in AIHA patients and in controls, with their 95% confidence intervals (95% CIs). Results During the study period, 9,663 incident AIHA patients were included. The median age was 69 years and 55.6 of the patients were female. The overall incidence of AIHA was 2.4 per 100,000 person-years (95% CI: 2.4 - 2.5). The incidence of AIHA in women during genital activity (15 - 45 years-old, 1.2 per 100,000 person-years, 95% CI: 1.1 - 1.3) was higher than in males of same age (0.7 per 100,000 person-years, 95% CI: 0.6 - 0.7). The incidence of AIHA was dramatically increased in the elderly (&gt;75 years of age: 10.5 per 100,000 person-years; 95% CI: 10.2 - 10.8) and the very elderly (&gt;90 years of age, 12.1 per 100,000 person-years; 95% CI: 11.1 - 13.2), as compared with people &lt;50 year-old (0.9 per 100,000 person-years; 95% CI: 0.9 - 1.0). Incidences were higher in males than in females in people &gt;65 year-old. This pattern was observed for both primary and secondary AIHA. There were no relevant variations of incidence by calendar months for both primary and secondary AIHA. AIHA was primary in 55.2% of cases, associated with hematological malignancy in 30.2% and with lupus in 5.2%. Evans syndrome accounted for 5.8% of AIHAs. The patients were matched with 47,753 controls. The overall follow-up in the cohort was 28,630 person-years. The 1-year cumulative incidence of death was 18.6% (95% CI: 17.8 - 19.4) in AIHA (in primary AIHA: 16.5%, 95% CI: 15.5 - 17.4), versus 3.1% (95% CI: 3.0 - 3.3) in controls. The 5-year cumulative incidence of death was 36.1% (95% CI: 34.9 - 37.2) in AIHA (in primary AIHA: 32.4%, 95% CI: 30.9 - 33.8) and 15.1% (95% CI: 14.7 - 15.5) in controls. The 1-year cumulative incidence of hospitalization for thrombosis was 6.0% (95% CI: 5.6 - 6.5) in AIHA (in primary AIHA: 5.7%, 95% CI: 5.1 - 6.4) versus 1.8% (95% CI: 1.7 - 1.9) in controls. The 5-year cumulative incidence of hospitalizations for thrombosis was 11.1% (95% CI: 10.4 - 11.8) in AIHA (in primary AIHA: 10.9%, 95% CI: 9.9 - 11.9) versus 7.0% (95% CI: 6.7 - 7.3) in controls. The 1-year cumulative incidence of hospitalization for infection was 22.9% (95% CI: 22.1 - 23.8) in AIHA (in primary AIHA: 20.9%, 95% CI: 19.8 - 22.0) versus 3.5% (95% CI: 3.3 - 3.6) in controls. The 5-year cumulative incidence of hospitalization for infection was 37.5% (95% CI: 36.4 - 38.6) in AIHA (in primary AIHA: 33.7%, 95% CI: 32.2 - 35.1) versus 13.5% (95% CI: 13.1 - 13.9) in controls. Conclusion The incidence of AIHA (primary or secondary) was more than ten times higher in the elderly and very elderly as compared with people &lt;50 year-old, suggesting a potential role for immunosenescence. As compared with the general population, AIHA patients had an increased risk of death, hospitalization for infection and thrombosis. It was similar in primary and secondary AIHA. Disclosures Moulis: Grifols: Research Funding; Amgen: Other: meeting attendance grant; Novartis SAS: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance grant, Research Funding.

Bone Marker-Directed Dosing of Zoledronic Acid for the Prevention of Skeletal Complications in Patients with Multiple Myeloma: Final Results of the Z-MARK Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4077-4077 ◽  
Author(s):  
Noopur Raje ◽  
Robert Vescio ◽  
Charles W. Montgomery ◽  
Joseph T Hadala ◽  
Ghulam Warsi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Zoledronic Acid ◽  
Bone Turnover ◽  
Disease Progression ◽  
Incidence Rate ◽  
Median Time ◽  
Research Funding ◽  
Bone Marker

Abstract Abstract 4077 Introduction: Treatment with zoledronic acid (ZOL, 4mg) has proven effective for reducing the risk of skeletal-related events (SREs) in patients (pts) with multiple myeloma (MM), with a SRE incidence rate as low as 27% after 3.7 years' median follow-up (Morgan G, et al. Lancet Oncology 2011;12:743-52). Pts with normal bone metabolism may not require as intense a treatment schedule as pts with accelerated bone turnover. The Z-MARK study evaluated if pts with 1–2 years of prior intravenous (IV) bisphosphonate (BP) therapy can be treated safely long-term with less-frequent ZOL dosing based on bone turnover markers. Methods: MM pts (N=121) who started IVBP therapy (ZOL or pamidronate) 1–2 years before enrollment and received ≥4 prior doses, with baseline calculated creatinine clearance (CrCl) of ≥30 mL/min, were enrolled. Pts received 4mg IV ZOL every (q) 4 or 12 weeks (wk) based on their most recent urinary N-telopeptide of type I collagen (uNTX) levels (q4 wk if uNTX ≥50 nmol/mmol Cr, q12 wk if uNTX <50 nmol/mmol Cr). Pts who developed a SRE or had disease progression requiring a change in MM therapy on study were treated q4 wk thereafter regardless of uNTX levels. The study's primary endpoint was the proportion of pts who experienced ≥1 SRE during study Year 1. Group A (ZOL q12 wk only, N=79) is compared with Group B (all others, N=42). Results: Of 121 pts enrolled, 52 discontinued early: 29 (36.7%) in A and 23 (54.8%) in B. Median time to discontinuation was ∼20 months (mo) in A and ∼24 mo in B. Median time on ZOL on study was 22.5 mo for A and 20.8 mo for B. The mean age was 63.8 years (range, 34–90) with approximately 1:1 male:female ratio. By International Staging System criteria, 81.0% in A and 69.1% in B were Stage I/II, while 15.2% and 19.0% were Stage III. Median time from initial MM diagnosis to enrollment was 18.4 mo in A and 18.6 mo in B. A majority of pts in both groups had ≥1 osteolytic lesions at enrollment (A, 65.8%; B, 76.2%). The median duration of prior IVBP therapy was 13.8 mo in A and 14.4 mo in B. At enrollment, 72.2% in A and 78.6% in B had ≥1 SRE. The baseline mean (standard deviation) for uNTX and calculated CrCl was 19.88 (8.8) nmol/mmol Cr, and 85.1 (31.8) mL/min in A and 24.1 (15.6) nmol/mmol Cr and 84.3 (40.0) mL/min in B. Four pts started ZOL at q4 wk vs 117 pts at q12 wk based on uNTX at study entry. Of 117 pts assigned to q12-wk dosing, 79 stayed on schedule throughout the study; 38 pts switched to q4 wk (14 for increased uNTX, 4 for SREs, and 20 for disease progression). Only 7 pts (5.8%; all in A) had a SRE in study Year 1 (3 pathologic fractures, 3 spinal cord compressions, 4 radiation to bone, 1 surgery to bone, 1 hypercalcemia of malignancy). In Year 2, only 5 pts (4.1%) had a SRE (1 pathologic fracture, 4 radiation to bone). Baseline uNTX (low: <28, high: ≥28) was predictive of SREs (hazard ratio=3.1, P=.06). Treatment was well-tolerated. The most common AEs were fatigue (26.4%), upper respiratory tract infection (24%), diarrhea (21.5%), pneumonia (21.5%), cough (20.7%), pyrexia (18.2%), arthralgia (17.4%), and nausea (17.4%); none were attributed to ZOL. Except for arthralgia, the incidence of these AEs was higher in B vs A. Serious AEs were reported in 29.1% in A and 59.5% in B. Overall, 19.8% of pts (15.2% A, 28.6% B) had an AE leading to ZOL discontinuation. At 48 wk, the median percentage change in uNTX was –13.3% in A and 0% in B. No change in the median serum Cr was observed in either group at 48 wk. Four deaths (2 from progression of MM, 1 from pneumonia, 1 unknown) were reported on study (not suspected to be related to ZOL). Four reports of osteonecrosis of the jaw (ONJ) were suspected to be related to ZOL (all in A, q12-wk dosing) at 22.2 mo median follow-up. Conclusions: The final Z-MARK results show that bone marker-directed dosing is feasible and safe in pts with 1–2 years of prior IVBP therapy. The low incidence of SREs on study shows that less-frequent IVBP dosing beyond 1–2 years continues to reduce the SRE risk and may reflect changing treatment patterns for MM that include therapies with bone protective effects. Baseline uNTX (≥28 nmol/mmol Cr) trended toward significance for predicting SREs. Finally, this study, which prospectively evaluated ONJ beyond 3 years, demonstrated an incidence rate of 3.3%. Further studies and additional follow-up are needed to determine the potential predictive value and long-term benefits of bone marker-directed ZOL dosing in MM pts after standard IVBP treatment. Disclosures: Raje: Amgen: Research Funding; Acetylon: Research Funding; Millenium: Consultancy; Celgene: Consultancy; Onyx: Consultancy; Eli-Lilly: Research Funding; Novartis: Consultancy. Off Label Use: Zoledronic acid (4 mg every 3–4 weeks) is indicated for the treatment of patients with multiple myeloma and patients with bone metastases from solid tumors. Vescio:Novartis Pharmaceuticals Corporation: Speakers Bureau. Hadala:Novartis Pharmaceuticals Corporation: Employment. Warsi:Novartis: Equity Ownership; Novartis: Employment. Ericson:Novartis Pharmaceuticals Corporation: Employment, Stocks Other. Anderson:Novartis Pharmaceuticals Corporation: Consultancy.

scholarly journals Long-term (>10-year) clinical follow-up after young embolic stroke/TIA of undetermined source

2019 ◽  
pp. 174749301988452 ◽  
Author(s):  
M Nassif ◽  
ME Annink ◽  
H Yang ◽  
TCD Rettig ◽  
YBWEM Roos ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Recurrent Stroke ◽  
Young Patients ◽  
Incidence Rates ◽  
Embolic Stroke ◽  
Vascular Events ◽  
Tertiary Center ◽  
New Onset

Background To date, the pathophysiology of first-ever and recurrent stroke/TIA still remains unclear in young patients with embolic stroke/TIA of undetermined source (ESUS). Clinical studies with long-term follow-up in young ESUS patients are necessary to investigate the underlying pathophysiology of first-ever and recurrent stroke/TIA in this patient population, in particular the role of new-onset atrial fibrillation. Aims Our aim was to study the long-term (>10-year) clinical outcome of young patients (<50 years) with ESUS. Methods This cohort study included all patients aged ≤ 50 years who underwent transoesophageal echocardiography for diagnostic work-up of ESUS during 1996–2008 from one tertiary center. All patients were contacted by telephone between September–November 2018 to update clinical information from medical records. The clinical outcomes of this study were incidence rates of all-cause and cardiovascular mortality, recurrent stroke/TIA, new-onset clinical AF, and ischemic vascular events. Results In total, 108 patients (57% female, mean age 40 ± 7.2 years [range 19–50 years], n = 72 stroke) were included. Across clinical follow-up (median 13[IQR 10–16] years), 24 patients died ( n = 14 cardiovascular). The 15-year incidence rate of recurrent stroke/TIA was 15% (incidence rate = 1.09[95%CI 0.54–1.65]/100 patient-years) and a 5.5% incidence of new-onset clinical AF (incidence rate = 0.44[95%CI 0.09–0.79]/100 patient-years) following ESUS. Conclusions The incidence of recurrent stroke/TIA is relatively high during long-term clinical follow-up of young patients with ESUS. In contrast, new-onset clinical AF is relatively low and therefore may not play an important part in the pathophysiology of first-ever and recurrent stroke/TIA of these patients.

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