Survival Outcomes of Patients with Therapy-Related Myelodysplastic Syndromes in the United States

Abstract Background: The development of therapy-related MDS (t-MDS) is a rare but highly fatal complication of cancer therapies, with varying leukemogenicity associated with individual chemotherapeutic agents and radiation modalities. In recent years, an increase in t-MDS incidence explained by increased use of cancer treatment combined with an increasing number of cancer survivors has been reported. We investigated changes in t-MDS outcomes over time among cancer patients (pts) treated with chemotherapy and radiation using data from population-based cancer registries in the Surveillance, Epidemiology and End Results (SEER) Program of the US. Methods: A previously validated R package (SEERaBomb) was used to query all 18 SEER registries to identify adult pts (≥15 years of age) with multiple types of primary malignancies who were treated with chemotherapy and radiation as part of their initial cancer treatment, and subsequently developed MDS. Pts were observed from the date of first diagnosis of a primary malignancy until occurrence of MDS as second cancer, death, loss to follow-up, or end of the study period, whichever occurred earlier. Cases of MDS that developed at least 1 year (yr) following diagnosis and treatment of a primary malignancy were classified as t-MDS according to the World Health Organization classification. Primary cancers associated with at least 100 t-MDS cases were included in the analysis. Survival probabilities were compared for pts with: (1) primary cancers who did and did not subsequently develop MDS, (2) primary (de novo) MDS, and (3) t-MDS. Multivariate Cox regression analysis was performed to identify factors associated with overall survival (OS) in the t-MDS cohort, including the following covariates: age group [adolescents and young adults (AYA) (15-39 yrs); middle-aged (40-59 yrs); and older adults (≥60 yrs)], sex, year of diagnosis, race, and primary cancer type. Tests of significance were based on two-sided hypothesis at the .05 level. Results: A total of 933,789 adult cancer pts diagnosed between the years 2001-2015 were assembled from all 18 SEER registries which included 926,552 primary cancers, 5,478 primary MDS cases, and 1,759 t-MDS cases [breast (528), lung (207), lymphoma (663) and prostate (361)]. Median survival of t-MDS in months (m) with (range) by primary site was as follows: breast: 17.5m (0.5-172.5); lymphoma: 10.5m (0.5-168.5); lung: 5.5m (0.5-88.5); prostate: 21.5m (0.5-170.5); and combined: 13.5m (0.5-172.5). Median latency periods in yrs with (range) to develop t-MDS were as follows: breast: 5 yrs (1-40); lymphoma: 5 yrs (1-38); lung: 2 yrs (1-21); prostate: 5 yrs (1-25); combined: 5 yrs (1-40). Figure 1 shows comparison of survival probabilities of primary malignancies with and without subsequent development of t-MDS over two treatment eras (2001-2006 and 2007-2015), organized by yr of diagnosis and primary cancer type. As expected, development of t-MDS was significantly associated with worse survival for all four primaries that contribute to the bulk of t-MDS cases. Figure 2 shows survival probabilities of primary (de novo) MDS versus t-MDS. In multivariate analyses of factors associated with survival in the t-MDS cohort, the hazard ratio (HR) of death was significantly higher in middle aged adults [vs AYA, 2.20 (95% CI 1.34-3.62)] and older adults (vs AYA, 2.39 (95% CI 1.47-3.90)], in lung cancer [vs breast, 2.98 (95% CI 2.31-3.84)] and in lymphomas [vs breast, 1.467 (95% CI 1.18-1.83)], but was not influenced by sex [female vs male, 0.94 (95% CI 0.819-1.079)], race {[white vs black, 1.0 (95% CI 0.839-1.195)], [white vs other, 0.957 (95% CI 0.795-1.151)]}, or year of diagnosis of t-MDS [2001-2006 vs 2007-2015, 1.025 (95% CI 0.923-1.139)]. Conclusions: In population-based analyses, the survival of t-MDS remains dismal with outcomes particularly worse with advancing age and following primary cancer sites that are typically managed with combined modality regimens including chemotherapy and radiation. Findings from the real-world population level data such as this should be used as outcome benchmarks in clinical trials to assess therapeutic effectiveness of experimental treatments. Disclosures Gerds: Apexx Oncology: Consultancy; Celgene: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Nazha:MEI: Consultancy. Carraway:Jazz: Speakers Bureau; FibroGen: Consultancy; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Agios: Consultancy, Speakers Bureau. Maciejewski:Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy. Majhail:Incyte: Honoraria; Anthem, Inc.: Consultancy; Atara: Honoraria. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

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Survival Outcomes of Patients with Therapy-Related Acute Myeloid Leukemia in the United States

Blood ◽

10.1182/blood-2018-99-119535 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2298-2298

Author(s):

Raffi Tchekmedyian ◽

Tomas Radivoyevitch ◽

Aaron T. Gerds ◽

Aziz Nazha ◽

Hetty E. Carraway ◽

...

Keyword(s):

Board Of Directors ◽

De Novo ◽

Population Based ◽

Cancer Type ◽

Cancer Therapies ◽

Primary Cancer ◽

Primary Malignancy ◽

Advisory Committees ◽

Lung Cancers ◽

Survival Probabilities

Abstract Background The development of therapy-related AML (t-AML) is a rare but fatal complication of cancer therapies, with varying leukemogenicity associated with individual chemotherapies and radiation modalities. In recent years, there is an increase in t-AML incidence explained by increased use of cancer therapies and increased cancer survivorship. We investigated changes in t-AML outcomes over time among cancer patients (pts) treated with chemotherapy and radiation using data from population-based cancer registries in the Surveillance, Epidemiology and End Results (SEER) Program of the US. Methods A previously validated R package (SEERaBomb) was used to query all 18 SEER registries to identify adult pts (≥15 years) with multiple types of primary malignancies who were treated with chemotherapy and radiation, and subsequently developed AML. Pts were observed from the date of first diagnosis of a primary malignancy until occurrence of AML as a second cancer, death, loss to follow-up or end of the study period, whichever occurred earlier. Cases of AML that developed at least 1 year following diagnosis and treatment of a primary malignancy were classified as t-AML. Primary cancers associated with at least 100 t-AML cases were included. Survival probabilities were compared for pts with: (1) primary cancers which did and did not subsequently develop AML, (2) primary (de novo) AML, and t-AML. Multivariate Cox regression analysis was performed to identify factors associated with overall survival (OS) in the t-AML cohort, including the following covariates: age group [adolescents and young adults (AYA) (15-39 years); middle-aged (40-59); and older adults (≥60)], sex, year of diagnosis, race, primary cancer type, and whether or not treatment was received for t-AML. Tests of significance were based on two-sided hypothesis at the .05 level. Results A total of 1,425,840 adult cancer pts diagnosed between the years 1973-2015 were assembled from all 18 SEER registries which included 1,392,784 primary cancers, 31,112 primary AML cases and 1,944 t-AML cases [breast (781), lung (205), lymphoma (612), and prostate (346)]. Median survival of t-AML in months (m) with (range) by primary site was as follows: breast: 5.5m (0.5-263); lymphoma: 4.5m (0.5-255.5); lung: 1.5m (0.5-178.5); and prostate: 3.5m (0.5-196.5); combined: 3.5m (0.5-263). Median latency periods in years (y) with (range) to develop t-AML were as follows: breast: 3y (1-38); lymphoma: 4y (1-30); lung: 2y (1-22); and prostate: 4y (1-18); combined: 4y (1-39) . Figure 1 shows comparison of survival probabilities of primary malignancies with and without subsequent development of t-AML over three time periods (1973-1990, 1991-2005 and 2006-2015) organized by year of diagnosis and primary cancer type. Development of t-AML was significantly associated with worse survival for all the four primaries that contribute to the bulk of t-AML cases. Figure 2 shows survival probabilities of primary (de novo) AML versus t-AML (all pooled cases). In multivariate analyses, the hazard ratio (HR) of death was significantly higher in older adults [vsAYA, 1.39 (95% CI 1.11-1.75)] but not middle-aged adults [vsAYA, 0.931 (95% CI 0.738-1.175)], lower in other races [vsCaucasian, 0.81 (95% CI 0.66-0.988)] but not in African Americans [vsCaucasian, 1.078 (95% CI 0.917-1.267)] and lower in those diagnosed between the years 2006-2015 [vs1973-1990, 0.69 (95% CI 0.58-0.82)]. Pts treated for their t-AML had a HR of death significantly lower than those who did not receive treatment [0.426 (95% CI 0.38-0.47)]. There was no significant difference in HR between male and female patients [0.971 (95% CI 0.839-1.123)]. When analyzed by treatment periods, there was no difference noted between the time periods 1973-1990 and 1991-2005 [0.878 (95% CI 0.737-1.045)]. Among primary cancer type, only those t-AML cases preceded by lung cancers had a significantly higher HR of death {[lung vsbreast, 1.56 (95% CI 1.27-1.92)]; [lymphoma vs breast, 1.006 (95% CI 0.847-1.194)]; [prostate vsbreast, 0.861 (95% CI 0.679-1.093)]. Conclusions In our population based analysis, we show that although the OS of t-AML is significantly worse than primary AML, those t-AML diagnosed and treated in recent years (2006-2015) had significantly better survival compared to earlier treatment periods. Among all primaries, outcomes of t-AML particularly following lung cancers are dismal compared to other primaries. Disclosures Gerds: Celgene: Consultancy; Apexx Oncology: Consultancy; CTI Biopharma: Consultancy; Incyte: Consultancy. Nazha:MEI: Consultancy. Carraway:FibroGen: Consultancy; Jazz: Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau; Novartis: Speakers Bureau. Maciejewski:Apellis Pharmaceuticals: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ra Pharmaceuticals, Inc: Consultancy. Majhail:Incyte: Honoraria; Anthem, Inc.: Consultancy; Atara: Honoraria. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees.

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Factors associated with sarcopenia screened by finger-circle test among middle-aged and older adults: a population-based multisite cross-sectional survey in Japan

BMC Public Health ◽

10.1186/s12889-021-10844-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Daiki Watanabe ◽

Tsukasa Yoshida ◽

Takashi Nakagata ◽

Naomi Sawada ◽

Yosuke Yamada ◽

...

Keyword(s):

Older Adults ◽

Smoking Status ◽

Multiple Logistic Regression Analysis ◽

Population Based ◽

Middle Aged ◽

Cross Sectional ◽

Factors Associated ◽

Mail Surveys ◽

Osaka Prefecture ◽

Middle Aged Adults

AbstractBackgroundPrevious epidemiological studies have demonstrated the prevalence and relationship of various factors associated with sarcopenia in older adults; however, few have examined the status of sarcopenia in middle-aged adults. In this study, we aimed to, 1) evaluate the validity of the finger-circle test, which is potentially a useful screening tool for sarcopenia, and 2) determine the prevalence and factors associated with sarcopenia in middle-aged and older adults.MethodsWe conducted face-to-face surveys of 525 adults, who were aged 40–91 years and resided in Settsu City, Osaka Prefecture, Japan to evaluate the validity of finger-circle test. The finger-circle test evaluated calf circumference by referring to an illustration printed on the survey form. The area under the receiver operating characteristic curves (AUROC) was plotted to evaluate the validity of the finger-circle test for screening sarcopenia and compared to that evaluated by skeletal muscle mass index (SMI) measured using bioimpedance. We also conducted multisite population-based cross-sectional anonymous mail surveys of 9337 adults, who were aged 40–97 years and resided in Settsu and Hannan Cities, Osaka Prefecture, Japan. Participants were selected through stratified random sampling by sex and age in the elementary school zones of their respective cities. We performed multiple logistic regression analysis to explore associations between characteristics and prevalence of sarcopenia.ResultsSarcopenia, defined by SMI, was moderately predicted by a finger-circle test response showing that the subject’s calf was smaller than their finger-circle (AUROC: 0.729, < 65 years; 0.653, ≥65 years); such subjects were considered to have sarcopenia. In mail surveys, prevalence of sarcopenia screened by finger-circle test was higher in older subjects (approximately 16%) than in middle-aged subjects (approximately 8–9%). In a multiple regression model, the factors associated with sarcopenia were age, body mass index, smoking status, self-reported health, and number of meals in all the participants.ConclusionsSarcopenia, screened by the finger-circle test, was present not only among older adults but also among middle-aged adults. These results may provide useful indications for developing public health programs, not only for the prevention, but especially for the management of sarcopenia.Trial registrationUMIN000036880, registered prospectively May 29, 2019, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042027

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Prevalence of household falls in long-lived adults and association with extrinsic factors

Revista Latino-Americana de Enfermagem ◽

10.1590/1518-8345.1646.2900 ◽

2017 ◽

Vol 25 (0) ◽

Cited By ~ 7

Author(s):

Silviane Galvan Pereira ◽

Claudia Benedita dos Santos ◽

Marlene Doring ◽

Marilene Rodrigues Portella

Keyword(s):

Older Adults ◽

Prevalence Ratio ◽

Household Survey ◽

Population Based ◽

Multiple Model ◽

Human Beings ◽

Extrinsic Factors ◽

Cross Sectional ◽

Factors Associated ◽

Selection Of Variables

Resume Objective: to identify the prevalence of falls among older adults and the extrinsic factors associated with them. Method: population-based cross-sectional study with 350 older adults. A household survey was conducted using a questionnaire addressing socio-demographic, clinical, and environmental characteristics. Data were analyzed using Stata Software V.10. Pearson’s chi-square test and logistic regression analysis were used with stepwise criteria for selection of variables in the model, with measures of effect expressed in Prevalence Ratio. For input into the multiple model, the variables with p ≤ 0.20 were considered. All ethical care regarding research on human beings has been observed and respected. Results: the prevalence of falls was 46.9%. The extrinsic factors associated with falls were: stairs, uneven floor and pets in the main entrance, lack of anti-slip loose throw rugs and slippery floor in the kitchen, lack of anti-slip loose throw rugs and objects on the floor in the room, lack of grab bars in the shower, lack of grab bars in the toilet and switch away from the bathroom door (p <0.05). Conclusion: falls are frequent in long-lived adults. The identification of the extrinsic factors associated with the occurrence of this event can help in its prevention.

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Long-Term Experience with Large Granular Lymphocytic Leukemia Evolving after Solid Organ and Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood-2019-130167 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1226-1226

Author(s):

Hassan Awada ◽

Reda Z. Mahfouz ◽

Jibran Durrani ◽

Ashwin Kishtagari ◽

Deepa Jagadeesh ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Viral Infections ◽

De Novo ◽

Post Transplantation ◽

Advisory Committees ◽

Hematopoietic Stem ◽

Post Transplant ◽

Stat3 Mutations

T-cell large granular lymphocyte leukemia (T-LGLL) is a clonal proliferation of cytotoxic T lymphocytes (CTL). T-LGLL mainly manifest in elderly and is associated with autoimmune diseases including rheumatoid arthritis (RA), B cell dyscrasias, non-hematologic cancers and immunodeficiency (e.g., hypogammaglobulinemia). LGL manifestations often resemble reactive immune processes leading to the dilemmas that LGLs act like CTL expansion during viral infections (for example EBV associated infectious mononucleosis). While studying a cohort of 246 adult patients with T-LGLL seen at Cleveland Clinic over the past 10 years, we encountered 15 cases of overt T-LGLL following transplantation of solid organs (SOT; n=8) and hematopoietic stem cell transplantation (HSCT; n=7). Although early studies reported on the occurrence of LGL post-transplant, these studies focused on the analysis of oligoclonality skewed reactive CTL responses rather than frank T-LGLL. We aimed to characterize post-transplantation T-LGLL in SOT and HSCT simultaneously and compare them to a control group of 231 de novo T-LGLL (cases with no history of SOT or HSCT). To characterize an unambiguous "WHO-defined T-LGLL" we applied stringent and uniform criteria. All cases were diagnosed if 3 out of 4 criteria were fulfilled, including: 1) LGL count >500/µL in blood for more than 6 months; 2) abnormal CTLs expressing CD3, CD8 and CD57 by flow cytometry; 3) preferential usage of a TCR Vβ family by flow cytometry; 4) TCR gene rearrangement by PCR. In addition, targeted deep sequencing for STAT3 mutations was performed and charts of bone marrow biopsies were reviewed to exclude other possible conditions. Diagnosis was made 0.2-27 yrs post-transplantation (median: 4 yrs). At the time of T-LGLL diagnosis, relative lymphocytosis (15-91%), T lymphocytosis (49-99%) and elevated absolute LGL counts (>500 /µL; 93%) were also seen. Post-transplantation T-LGLL were significantly younger than de novo T-LGLL, (median age: 48 vs. 61 yr; P<.0001). Sixty% of post-transplantation T-LGLL patients were males. Fifteen% of patients had more cytogenetic abnormalities compared to de novo T-LGLL, had a lower absolute LGL count (median: 4.5 vs. 8.5 k/µL) and had less frequent neutropenia, thrombocytopenia and anemia (27 vs. 43%, 33 vs. 35% and 20% vs. 55%; P=.01). TCR Vb analysis identified clonal expansion of ≥1 of the Vb proteins in 60% (n=9) of the patients; the remaining 40% (n=6) of the cases had either a clonal process involving a Vb protein not tested in the panel (20%; n=3) or no clear expansion (20%; n=3). Signs of rejection were observed in 20% (n=3/15) and GvHD in 13% (n=2/15) of the patients. Post-transplantation, 27% of cases presented with neutropenia (absolute neutrophil count <1.5 x109/L; n=4), 33% with thrombocytopenia (platelet count <150 x109/L; n=5) and 25% with anemia (hemoglobin <10 g/dL; n=3). T-LGLL evolved in 10 patients (67%; 10/15) despite IST including cyclosporine (n=5), tacrolimus (n=4), mycophenolate mofetil (n=5), cyclophosphamide (n=1), anti-thymocyte globulin (n=1), and corticosteroids (n=6). Lymphadenopathy and splenomegaly were seen in 13% (n=2) and 33% (n=5) of the patients. Other conditions observed were MGUS (20%; n=3) and RA (7%; n=1). Conventional cytogenetic showed normal karyotype in 89% (n=11, tested individuals 13/15). Somatic STAT3 mutations were identified in 2 patients. Sixty% of cases (n=9) were seropositive for EBV when tested at different time points after transplant. Similarly, 53% (n=8) were seropositive for CMV, of which, 5 were positive post-transplantation and 3 pre-/post-transplantation. The complexity of T-LGLL expansion post-transplantation might be due to several mechanisms including active viral infections, latent oncogenic viral reactivation and graft allo-antigenic stimulation. However, in our cohort graft rejection or GvHD was encountered in a few patients (2 allo-HSCT recipients). Autoimmune conditions were present in 50% of SOT recipients (n=4/ 8, including RA, ulcerative colitis, systemic lupus erythematosus). Some of our patients also had low immunoglobulin levels. Overt EBV (post-transplant lymphoproliferative disorder) and CMV reactivation was diagnosed in only 27% (4/15) of the patients. In sum we report the long term follow up of a cohort of T-LGLL and emphasize the expansion of T-LGLL post-transplant highlighting the difficulty in assigning one unique origin of LGLL. Disclosures Hill: Genentech: Consultancy, Research Funding; Takeda: Research Funding; Celegene: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Honoraria; Amgen: Research Funding; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Research Funding; AstraZeneca: Consultancy, Honoraria. Majhail:Atara Bio: Consultancy; Mallinckrodt: Honoraria; Nkarta: Consultancy; Anthem, Inc.: Consultancy; Incyte: Consultancy. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Alexion: Consultancy; Novartis: Consultancy.

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Prospective Population-Based Analysis of Characteristics and Therapy Options in AML: The Case of Catalonia (PERIS Project)

Blood ◽

10.1182/blood-2020-139160 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 32-33

Author(s):

Montserrat Hoyos ◽

Ana Garrido ◽

Montserrat Arnan ◽

Marina Diaz-Beyá ◽

Olga Salamero ◽

...

Keyword(s):

Clinical Trials ◽

Board Of Directors ◽

Hematopoietic Cell Transplantation ◽

Clinical Laboratory ◽

Laboratory Data ◽

Population Based ◽

Advanced Age ◽

Age Group ◽

Advisory Committees ◽

Low Intensity

Introduction:Acute myeloid leukemia (AML) real-world incidence has been investigated in a limited number of European countries such as Sweden, Denmark and a few others. These prospective population-based analyses give a more precise idea of AML as a health problem than registry data from cooperative groups or other sources, that usually include selected cases as part of research studies and/or therapy trials. In October 2016, the Autonomous Government of Catalonia funded a project (PERIS SLT002/16/00433) to prospectively collect all AML cases from our territory. Objective:To investigate the incidence, characteristics and treatment decisions in all consecutive AML patients diagnosed in Catalonia between January 2017 and December 2019. Methods:Inclusion criteria were diagnosis of AML according the WHO 2016 criteria, both primary and secondary (APL excluded) with an age >18 years. The project was disseminated to all hospitals from Catalonia regardless of their size, having at least one hematologist. A specific informatics tool was implemented for remote reporting of the cases. All data were anonymized. In parallel, a circuit for centralized bio banking of patients' samples was designed. The database included the main clinical, laboratory data as well as the initial therapeutic approach. Cases included in our CETLAM group cooperative studies were automatically linked to the trial database for collecting detailed information. Statistical analyses were performed with R packages. Results:Assuming an incidence of AML of 4 cases per 100,000 inhabitants (based on previous reported data from others), we expected 912 cases during three years in the 7,6 million population of Catalonia. Our prospective registry included 750 consecutive AML patients, 82% of the expected cases. The remaining 18% could be explained by the exclusion of APL, age below 18 years, or underreporting. Seventy percent of patients (n=527) were diagnosed and treated in the 5 large University Hospitals from Barcelona and the two adjacent cities (Badalona and Hospitalet). Table 1 shows the main characteristics of the patients. Among the 390 patients up to 70 years, 272 (70%) were enrolled in the CETLAM AML-12 protocol that included intensive chemotherapy (ICT) and risk adapted hematopoietic cell transplantation (HCT). Forty-one additional patients (11%) in this age group received other ICT in different clinical trials. A remaining 73 patients (20%) were treated with other intensive or non-intensive approaches outside trials. In the group of 360 patients older than 70 years only a 33% (n= 119) were treated under the risk-adapted CETLAM AML-16 protocol for elderly AML patients. This trial included ICT as in the CETLAM-12 in case of favorable genetic features; this was received by 13 of the 119 patients (11%) enrolled. The remaining patients of CETLAM-16 were treated with low-intensity chemotherapy (oral fludarabine, subcutaneous (SC) cytarabine and G-CSF or azacytidine) and 97 additional elderly patients were included in other clinical trials mostly with targeted and hypomethylating agents (27%). Other active therapies outside trials (usually low-intensity) were administered in 50 additional patients (14%) whereas the remaining 94 patients (26%) only received supportive measures (transfusions, hydroxyurea, antibiotics, palliation, or no treatment), because of one or more of the following: advanced age, poor AML features or severe clinical condition. Overall survival (OS) of the whole series at 2 years was 31±2% (CI: 27-35). Patients younger than 70 years had a 2-year OS of 47±3% (CI: 41-53) compared to 11±3% (CI: 7-17) for those above 70 years (p<0.001) (Image 1). Conclusions:This prospective study is highly representative of the diagnosis and treatment of AML in Catalonia. The median age at diagnosis was 70 years. Of note, 81% of patients up to 70 years were enrolled in ICT trials. The proportion of patients in trials in the elderly group was lower although still remarkable (60%). In this advanced age group, a 26% of patients were treated with supportive measures only. Despite the high inclusion rate in clinical trials, only one third of newly diagnosed AML patients have the probability to survive at 2 years, with a dismal outcome in those above 70 years. Therefore, the investigation of novel and more effective treatments remains mandatory. This series will be detailed and updated during the meeting. Disclosures Salamero: Pfizer:Consultancy;Jazz Pharmaceuticals:Consultancy, Honoraria;Daichii Sankyo:Honoraria;Novartis:Consultancy, Honoraria;Celgene:Consultancy, Honoraria.Olivera:BAYER:Consultancy;Pfizer:Consultancy, Speakers Bureau;Daiichi Sankyo:Consultancy, Speakers Bureau;Boehringer Ingelheim:Consultancy, Speakers Bureau.Sureda Balari:Celgene:Consultancy, Honoraria;Merck Sharpe and Dohme:Consultancy, Honoraria, Speakers Bureau;Sanofi:Consultancy, Honoraria;Novartis:Consultancy, Honoraria;Gilead/Kite:Consultancy, Honoraria;Janssen:Consultancy, Honoraria;Incyte:Consultancy;Roche:Honoraria;BMS:Speakers Bureau;Celgene/Bristol-Myers Squibb:Consultancy, Honoraria;Takeda:Consultancy, Honoraria, Speakers Bureau.Ribera:Pfizer, Amgen:Research Funding;Pfizer, Amgen, Ariad, Novartis:Consultancy, Speakers Bureau.Sierra:Jazz Pharmaceuticals:Research Funding;Pfizer:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Daiichi Sankyo:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Astellas:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead-Kite:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Clinically Suspected Cast Nephropathy: A Retrospective, Multi-Center, Real-World Study

Blood ◽

10.1182/blood-2019-124336 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5553-5553

Author(s):

Agoston Gyula Szabo ◽

Jonathan Thorsen ◽

Charlotte Toftmann Hansen ◽

Maja Ølholm Vase ◽

Manuela Teodorescu ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Serum Creatinine ◽

Board Of Directors ◽

Kidney Biopsy ◽

Population Based ◽

First Line ◽

Advisory Committees ◽

Cast Nephropathy ◽

Initiation Of Therapy

INTRODUCTION Myeloma cast nephropathy (CN) is the most common form of monoclonal immunoglobulin-mediated kidney disease, resulting from the precipitation of excessive amounts of monoclonal serum free light chains (sFLC) and causing around 70% of the cases of dialysis-dependent renal failure in multiple myeloma (MM)(Heher et al. 2013; Nasr et al. 2012; Sanders et al. 1991). In patients with acute renal failure, the finding of a high sFLC concentration with an abnormal sFLC ratio raises the clinical suspicion of CN (Hutchison et al. 2011). Although the histopathologic diagnosis of CN is established by renal biopsy, in routine clinical practice, the diagnostic yield of this procedure is often outweighed by the urgent need of anti-myeloma treatment and the risk of procedure-related complications. Recruitment of patients with CN into clinical trials is challenging and therefore real-world data on clinically suspected CN are necessary to understand the clinical characteristics, treatment and prognosis of these patients (Bridoux et al. 2017; Hutchison et al. 2019). METHODS We searched the population-based Danish Multiple Myeloma Registry for patients diagnosed with MM according to the International Myeloma Working Group criteria between 1st of January 2013 and 31st of December 2017 with a serum creatinine concentration of 200 µg/L or higher and a sFLC concentration of 1000 mg/L or higher at diagnosis. We conducted a retrospective patient chart review in eight Danish centers and assessed baseline characteristics, biopsy results, and overall survival. Anti-myeloma treatment, sFLC levels and renal function were registered during the first 12 months after MM diagnosis. RESULTS We identified 181 patients (176 with accessible clinical records). The median age was 72 years, the median serum creatinine was 384 µg/L, the median involved sFLC concentration was 5960 mg/L and dialysis dependent renal failure was present in 35%. Pre-myeloma estimated glomerular filtration rate (eGFR) was available in 80%, the median eGFR was 66 ml/min/1.73 m2. A kidney biopsy was carried out in 21% of patients and showed CN in 70% of cases. The median time from first sFLC measurement to initiation of therapy was 4 days. The number of lines of therapy ranged between zero and six. 173 patients received one, 35 patients received two and 14 patients received three lines of therapy during the first 12 months from diagnosis. High-dose melphalan with autologous stem cell transplantation (HDT-ASCT) was carried out in 45 (26%) patients. Bortezomib was administered as part of the first-line regimen in 163 (94%) patients. The most common first-line regimens were bortezomib-dexamethasone (n=67) and cyclophosphamide-bortezomib-dexamethasone (n=46). The first line of therapy resulted in very good partial response or better in 50% (Figure 1A), but was discontinued due to death, toxicity or progressive disease in 38% of patients. Dialysis dependency, eGFR and involved sFLC concentration were assessed at the end of the first cycle, at three months, six months and 12 months after initiation of therapy. At all these time points, achievement of renal recovery was associated with the magnitude of reduction of involved sFLC (Figure 1B). The median overall survival was 3.3 years (Figure 1C). At 12 months after diagnosis, 68% of patients were alive and 15% were dialysis dependent. Reduction of the initial involved sFLC concentration to ≤ 10% at three months was strongly associated with longer OS in a multivariate cox regression analysis adjusted for age and HDT-ASCT; hazard ratio 0.42, p=0.003. CONCLUSION In conclusion, we assessed a population-based cohort of newly diagnosed MM patients presenting with a serum creatinine of 200 µg/L or higher together with a sFLC of 1000 mg/L or higher. Although CN could have been clinically suspected in these cases, a kidney biopsy was only performed in one fifth of the population. Bortezomib-based therapy was initiated quickly and resulted in deep responses in most patients. Approximately one third of patients died within a year from MM diagnosis. Achievement of early and deep reduction in involved sFLC resulted in longer OS. Figure 1 Disclosures Szabo: Janssen: Consultancy. Vangsted:Takeda: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria; Celgene: Honoraria; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Plesner:Celgene: Consultancy; AbbVie: Consultancy; Genmab: Consultancy; Oncopeptides: Consultancy; Takeda: Consultancy; Janssen: Consultancy, Research Funding.

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Treating Acute Leukemia during the COVID-19 Pandemic: A Multicenter Latin American Registry

Blood ◽

10.1182/blood-2020-139018 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 41-42

Author(s):

Roberta Demichelis ◽

Martha Alvarado ◽

Jule F Vasquez ◽

Nancy Delgado ◽

Cynthia Gómez ◽

...

Keyword(s):

High Risk ◽

Maintenance Therapy ◽

Acute Leukemia ◽

Board Of Directors ◽

Latin American ◽

Refractory Disease ◽

Newly Diagnosed ◽

Advisory Committees ◽

Factors Associated ◽

Latin American Countries

Introduction The COVID-19 pandemic has affected the entire world. Health systems have been affected in such a way that patients with diseases other than COVID-19 have suffered serious consequences. In Latin America, the disease has emerged in a fragile system with more disparities, making our patients more vulnerable. Acute leukemia patients have a high risk of severe COVID-19 disease. Various expert recommendations have emerged with the aim of minimizing the risk of COVID-19 without affecting leukemia-related outcomes. However, multiple logistical issues tangentially associated with the pandemic have also appeared, potentially limiting the quality of management of these patients. The objective of this study was to register treatment modifications associated with the COVID-19 pandemic and its short-term consequences in Latin American countries. Methods We included patients older than 14 years, from 14 centers of 4 Latin American countries (Mexico, Peru, Guatemala and Panama), with the diagnosis of acute leukemia, who were on active treatment since the first case of COVID-19 was documented in each country. We documented their baseline characteristics and followed the patients prospectively until July 15, were data-cutoff for this pre-planned analysis was performed. The primary outcome was the incidence of COVID-19 disease and its complications. Secondary outcomes included treatment and consult modifications, and cause of death during the study period. Logistic regression was performed to determine factors associated with COVID-19 and all-cause mortality. Results We recorded the information of 635 patients: 58.1% Ph-negative ALL, 25.7% AML, 9% APL and 7.2% Ph+ALL. The median age was 35 years (14-90 years); 58.8% were consideredf high-risk patients. The majority were on CR (68.3%) receiving consolidation or maintenance therapy, while 14.5% were newly diagnosed and 17.2% with relapsed/refractory disease. The majority (91.8%) were treated in centers that were also receiving COVID-19 patients, 40.2% in centers were patients could not be electively hospitalized for leukemia treatment because of the COVID-19 pandemic. The COVID-pandemic led to treatment-modifications in 40.8% of the cases. Reasons for modifications were associated with logistical issues (22.4%), medical decisions (15.1%) or patient choice (3.3%). The most frequent modification was chemotherapy delay (17.3%) followed by regimen modification (13.4%) and dose-reductions (10.1%). (Figure 1) 83 patients (13.1%) developed COVID-19 disease, the majority mild-moderate disease (54.2%), 27.7% severe disease and 18.1% critically ill; 27.7% required mechanical ventilation and 37.7% died from COVID-19 disease, representing 4.9% of the entire cohort. We identify as risk factors for COVID-19 disease the presence of active leukemia (newly diagnosed or relapsed) (OR 3.46 [95% CI: 2.16-5.5], p<0.001), high-risk leukemia (OR 1.63 [95% CI: 1.54-4.52], p<0.001) and being treated in a center were elective hospitalization was possible (OR 2.17 [95% CI 1.29-3.67], p=0.004). Treatment modifications, appointment prolongations or the use of virtual consultation were not associated with a reduction in the risk of COVID-19. On the other hand, 16.7% of patients died during period analyzed due to leukemia (57.5%), COVID-19 (29.2%) or treatment related-mortality (13.2%). Independent factors associated with mortality were AML vs. ALL (OR 1.89 [95% CI: 1.12-3.18], p=0.016), relapsed-refractory disease (OR 8.34 [95% CI: 4.83-14.41], p<0.001), induction/consolidation vs. maintenance therapy (OR 2.20 [95% CI: 1.25-3.18], p<0.001) and the use of virtual consultation (OR 0.35 [95% CI: 0.13-0.94] p=0.037). (Table 1) Discussion/Conclusions The COVID-19 pandemic led to significant modifications in the standard of care treatment of patients with acute leukemia. The incidence of COVID-19 disease in acute leukemia patients was considerable and more than a third of the patients with acute leukemia and COVID-19 disease died. Despite a short-follow up, 16.7% of the patients died and leukemia-related deaths were the most frequent. In low- and middle-income countries with fragile health systems, the collateral damage for patients with acute leukemia may be just as important as the direct consequences of COVID-19. Disclosures Alvarado: Roche: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Alexion: Speakers Bureau. De la Peña-Celaya:Amgen: Speakers Bureau; Janssen: Speakers Bureau; Novartis: Speakers Bureau. Perez:Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau. Gomez-Almaguer:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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10-Year Mortality in Patients with Sickle Cell Disease from a Large Population-Based Cohort

Blood ◽

10.1182/blood-2020-141613 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 56-56

Author(s):

Kristina Lai ◽

Marianne McPherson Yee ◽

Beatrice Gee ◽

Maa-Ohui Quarmyne ◽

Ross M. Fasano ◽

...

Keyword(s):

Mortality Rate ◽

Board Of Directors ◽

Sickle Cell ◽

Bacterial Infections ◽

Mortality Rates ◽

Population Based ◽

Cell Disease ◽

Adult Care ◽

Advisory Committees ◽

Hb S

Background Mortality rates and causes of death in children with sickle cell disease (SCD) have changed significantly over the past several decades. With ongoing improvements in standards of care, modern mortality estimates must be updated. Children's Healthcare of Atlanta (CHOA) houses one of the largest pediatric SCD programs in the country. This analysis reviews mortality in children with SCD who were treated at CHOA between June 2010-June 2020. Methods We reviewed the CHOA's Sickle Cell Clinical Database (SCCD) for deceased patients. Demographics, SCD genotype, date and age at death, healthcare utilization, hydroxyurea (HU) use, chronic transfusion therapy (CTT), and bone marrow transplant (BMT) were obtained from the SCCD. Cause of death and history of significant comorbidities were abstracted from the medical record. Mortality rates were calculated using person-time for all CHOA SCD patients and population-based mortality was obtained from CDC WONDER Online Database. Results A total of 3,698 patients with SCD were seen at CHOA from June 2010-June 2020 and accounted for 19,998 person-years. Of the 46 patients who died during that time, all but 1 patient had been seen in the CHOA Sickle Cell Outpatient Clinic at least once. That patient received SCD care at a different institution, died from complications of a non-SCD related disease following transfer to CHOA, and was excluded from analysis. Of the 45 remaining patients (178 person-years), the majority were sickle cell anemia genotypes (n=37, 82%; Hb SS or Hb S β0 thalassemia), followed by Hb SC (n=5, 11.1%) and Hb S β+ thalassemia (n=3, 6.7%); 53% (n=24) were female. The average age at death was 12.8 years (1.0-22.8 years). Twenty-one (46.7%) patients had ever been treated with HU and 11 (24.4%) were currently on HU at the time of last contact (either death or last CHOA encounter). Eleven (24.4%) patients had ever been treated with CTT, and 3 (8.9%) were being treated with CTT at time of last contact. In comparison, during the same time period an average of 58% and 12% of the overall CHOA SCD population were being treated with HU and CTT, respectively. Forty-one patients had at least 1 SCD-related encounter at CHOA within 12 months prior to death. For the 4 patients who had not been seen at CHOA within 12 months, the average time since last contact was 1.72 years (1.03 - 2.7 years). Eighty percent (n=8) of the 10 patients who died at age >19 had either recently transitioned to adult care or had documentation of a transition plan. During this 10-year period, the crude death rate was 2.3 per 1,000 person-years. The majority of deaths (62%, n=28) were attributable SCD-related causes and corresponded to a cause-specific mortality rate of 1.40 per 1,000 person-years. The remaining 38% (n=17) of deaths were caused by complex non-SCD comorbidities or accidental trauma and corresponded to a non-SCD related mortality rate of 0.85 per 1,000 person-years. In comparison, the mortality rate for African American persons age <22 in Georgia from 2009-2018 was 0.9 per 1,000 person-years. Of the 28 patients who died due to an SCD-related cause: 12 (27%) experienced an acute illness related to SCD, 4 (9%) succumbed to acute bacterial infections, 3 (7%) died from complications of SCD treatment (1 procedure-related, 2 drug-induced hemolytic anemia), and 1 (2%) died from complications of BMT. Nine (20%) had either recently transitioned to adult care or were lost to follow-up and had no significant non-SCD comorbidities, therefore cause of death was unknown. Of the 17 non-SCD related deaths, 16 (36%) were due to complex non-SCD comorbidities (including cancers, autoimmune disorders, and congenital heart disease) and 1 (2%) from an accidental trauma. Conclusions To our knowledge, this is the largest and most recent study of mortality in patients with SCD from a single institution. Overall, the demographics of deceased patients were similar to those of the CHOA SCD population as a whole. This cohort indicates that trends in mortality of children with SCD have largely shifted away from bacterial infections to other complications of SCD, subsequent treatments, or comorbidities. Our data confirm that patients nearing transition to adult care are at high risk of mortality. This study is limited to deaths that are known to the CHOA system, so future analyses will expand this cohort to include data from death certificates and CDC's National Death Index. Disclosures Lane: FORMA Therapeutics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees.

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Clinical manifestations and factors associated with mortality from COVID ‐19 in older adults: Retrospective population‐based study with 9807 older Brazilian COVID‐19 patients

Geriatrics and Gerontology International ◽

10.1111/ggi.14061 ◽

2020 ◽

Vol 20 (12) ◽

pp. 1177-1181

Author(s):

Carlos DF de Souza ◽

Amanda J de Arruda Magalhães ◽

Ayara JPD Lima ◽

Danielle N Nunes ◽

Érika de Fátima Machado Soares ◽

...

Keyword(s):

Older Adults ◽

Clinical Manifestations ◽

Population Based ◽

Population Based Study ◽

Factors Associated

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The Characteristics, Treatment Patterns, and Outcomes of Older Adults with Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-118660 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4463-4463

Author(s):

Mark A. Fiala ◽

Tanya M. Wildes ◽

Mark A. Schroeder ◽

Armin Ghobadi ◽

Keith E. Stockerl-Goldstein ◽

...

Keyword(s):

Older Adults ◽

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Performance Status ◽

Patient Characteristics ◽

Treatment Patterns ◽

Advisory Committees ◽

Improved Outcomes ◽

Immunomodulatory Drug

Abstract Background: Advances in the treatment for multiple myeloma (MM) have dramatically improved outcomes for younger patients. Older adults, particularly those 80 years of age or older at diagnosis, have seen more modest gains. MM incidence increases with age, and as more of the population is living later into life, the segment of the MM population over 80 will continue to grow. In this study, we sought to better understand the characteristics, treatment, and outcomes of older patients with MM. Methods: We identified all patients diagnosed with MM at age 80 or older in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2007-2013 to determine incidence and outcomes. Subset analysis was then performed on patients included in the SEER-Medicare linked database who were enrolled in Medicare Parts A, B, and D to further explore patient characteristics and treatment patterns. Results: The incidence of MM increases over age, peaking after age 80. The annual incidence for those aged 65-69, 70-74, 75-79, 80-84 and 85+ was 24.4, 32.7, 39.5, 42.8 and 36.4 per 100,000, respectively. Based on 2010 US population estimates, approximately 4,500 new cases of MM were diagnosed annually 2007-2013 in patients age 80 or older. In that period, 8,093 cases, approximately 1,150 per year, were reported to SEER. The estimated median overall survival (OS) of these patients was 14 months (95% CI 13.2-14.8). The estimated relative 12 month survival was 58.9% (95% CI 57.4-60.4) compared to their peers without cancer. Of the 8,093 cases of MM reported to SEER during the study period, 2,385 were present in the SEER-Medicare linked dataset. Of these, 225 were identified as smoldering MM using a previously established algorithm (Fiala, et al, JCOCCI, 2018) and excluded leaving 2,160 for the analyses. The median age was 84 (range 80-100) and 55% were female. 81% were white, 13% black or African-American, and 6% another race. At disease presentation, 22% had claims indicating hypercalcemia, 61% renal failure or chronic kidney disease, 59% anemia, and 34% MM bone involvement. The estimated median OS was 13.4 months (95% CI 12.2-15.1). Only 52% of patients had claims indicating they received systemic MM treatment within 6 months post-diagnosis. Nearly all that did received novel agents; 38% received bortezomib-based treatment, 41% immunomodulatory drug (IMID)-based, and 14% both. The others received antineoplastic chemotherapies such as melphalan or cyclophosphamide. Interestingly, bortezomib utilization increased incrementally from 25% of patients treated in 2007 to 62% in 2013 while IMID utilization declined from 67% to 49%. The median OS of those receiving treatment was 21 months (95% CI 18.5-23.1) compared to 6.3 months (95% CI 5.3-7.3) for those who did not (p <0.0001). MM treatment was associated with a 26% decrease in hazard for death (aHR 0.74; 95% CI 0.67-0.82; p < 0.0001) independent of age, race, gender, poverty, comorbidities, and proxy measures of performance status. Outcomes improved for patients in more recent years; the hazard for death decreased by 3% (HR 0.97; 95% CI 0.94-0.99; p = 0.0096) each year 2007-2013. This can be attributed to increasing treatment rates. In 2007, only 41% of patients received treatment compared to 61% in 2013. After controlling for MM treatment, the year of diagnosis was no longer a significant predictor of survival. Conclusions: The outcomes of patients with MM over 80 years old are still relatively poor; nearly half of the patients do not receive systemic treatment and for those who do the median OS is just 21 months. The population over 80, when MM incidence peaks, is projected to triple over the next few decades. It is imperative that we improve our understanding of the needs of this vulnerable subgroup of patients of MM. Disclosures Schroeder: Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vij:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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