scholarly journals Improved Survival in AL Amyloidosis: A Population-Based Study on 1,430 Patients Diagnosed in Sweden 1995-2013

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4448-4448 ◽  
Author(s):  
Brendan M. Weiss ◽  
Sigrun H Lund ◽  
Magnus Bjorkholm ◽  
Adam D. Cohen ◽  
Laura Dember ◽  
...  
Keyword(s):  
Overall Survival ◽  
Plasma Cell ◽  
Research Funding ◽  
Survival Rates ◽  
Population Based ◽  
Al Amyloidosis ◽  
Population Based Study ◽  
Cell Therapies ◽  
Entire Cohort ◽  
Over Time

Abstract Introduction: AL amyloidosis (AL) is a plasma cell disorder characterized by life-threatening vital organ dysfunction resulting in nearly a third of patients dying within the first year of diagnosis. The only available therapies are anti-plasma cell chemotherapy agents, which reduce the toxic and amyloidogenic immunoglobulin light chains. We have previously shown improved survival in multiple myeloma (MM) due to novel anti-plasma cell therapies. Studies from specialty amyloid centers have also shown improved survival in AL, but this has never been studied in a population-based setting. Methods: By using the nationwide Swedish Patient Registry we identified all individuals registered with AL amyloidosis (defined as more than one occurrence of the ICD-code E85.8 and E85.9) in Sweden 1995-2013. By using the Total Population Registry we identified four matched controls for each case of amyloidosis, matched by gender and year of birth, and the controls had to be alive at the time of diagnosis for the corresponding AL-amyloidosis case. By using the Cause of Death Registry we obtained information on date of death, with follow-up through 2013. Overall survival (OS) was analyzed using Kaplan-Meier method and Cox proportional model, adjusting for age, gender, and calendar period of diagnosis. The cohort was divided into 4 calendar periods to evaluate changes in overall survival (OS) over time. Results: We identified 1,430 AL patients; mean age at diagnosis of 66.3 years; male gender 58.5%. A diagnosis of MM was made in 10.7% of patients, 3.6% after the AL diagnosis (AL-MM) and 7.1% before the AL diagnosis (MM-AL). Compared to matched controls, AL patients in the entire cohort had a median OS of 1.72 years, median OS was not reached for controls (p<0.001). The median OS of MM-AL was 0.51 years, AL-MM 0.88 years and AL 1.87 years (p<0.001). Median OS for AL patients improved significantly over time: 0.77 years for 1995-99, 1.37 years for 2000-04, 1.85 years for 2005-09, and 3.48 years for 2010-2013 (p for trend <0.001). Survival improvements over time were observed in both those younger and older than age 65. The 1-year survival for AL patients was: 43% for 1995-1999, 58% for 2000-2004, 59% for 2005-2009 and 70% 2010-2013 (p<0.001). The 2-year survival rates: 30% for 1995-1999, 42% for 2000-2004, 49% for 2005-2009 and 61% 2010-2013 (p<0.05). Conclusions: In the first population-based study of outcomes in AL, based on almost 1,500 patients diagnosed during almost 20 years, we found that OS has improved over time. The most probable explanation is the availability of highly-effective anti-plasma cell agents and possibly improvement in supportive care. We have also demonstrated an improvement in early mortality in AL amyloidosis possibly due to earlier recognition of disease and prompt anti-plasma cell chemotherapy. This novel finding deserves further investigation. Figure 1 Figure 1. Disclosures Weiss: Prothena: Other: Travel, accommodations, Research Funding; GlaxoSmithKline: Consultancy; Millennium: Consultancy, Other: Travel, accommodations; Janssen: Consultancy, Other: Travel, accommodations, Research Funding; Novartis: Consultancy. Cohen:Bristol-Meyers Squibb: Consultancy, Research Funding; Janssen: Consultancy. Landgren:Amgen: Honoraria, Research Funding; BMS: Honoraria; Celgene: Honoraria, Research Funding; Takeda: Honoraria; Merck: Honoraria; Medscape Myeloma Program: Honoraria.

scholarly journals Time Trends and Prognostic Factors for Overall Survival in Myxoid Liposarcomas: A Population-Based Study

Sarcoma ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jules Lansu ◽  
Winan J. Van Houdt ◽  
Michael Schaapveld ◽  
Iris Walraven ◽  
Michiel A. J. Van de Sande ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
The Netherlands ◽  
Metastatic Disease ◽  
Lower Limb ◽  
Tumor Size ◽  
Tumor Location ◽  
Population Based ◽  
Population Based Study ◽  
Over Time

Background. The purpose of this study was to evaluate the overall survival (OS) and associated characteristics for patients with Myxoid Liposarcoma (MLS) over time in The Netherlands. Methods. A population-based study was performed of patients with primary localized (n = 851) and metastatic (n = 50) MLS diagnosed in The Netherlands between 1989 and 2016, based on data from the National Cancer Registry. Results. The median age of the MLS patients was 49 years, and approximately two-thirds was located in the lower limb. An association was revealed between age and the risk of having a Round Cell (RC) tumor. OS rates for primary localized MLS were 93%, 83%, 78%, and 66% after 1, 3, 5, and 10 years, respectively. The median OS for patients with metastatic disease at diagnosis was 10 months. Increasing age (Hazard Ratio (HR) 1.05, p=0.00), a tumor size >5 cm (HR 2.18; p=0.00), and tumor location (trunk HR 1.29; p=0.09, upper limb HR 0.83; p=0.55, and “other” locations HR 2.73; p=0.00, as compared to lower limb) were independent prognostic factors for OS. The percentage of patients treated with radiotherapy (RT) increased over time, and preoperative RT gradually replaced postoperative RT. In contrast to patients with localized disease, significant improvement of OS was observed in patients with metastatic disease over time. Conclusions. In this large nationwide cohort, tumor size and tumor location were independent prognostic factors for OS. Furthermore, a higher probability of an RC tumor with increasing age was suggested. An increased use of RT over the years did not translate into improved OS for localized MLS.

scholarly journals Trends in Overall Survival and Treatment Patterns in Two Large Population-Based Cohorts of Patients with Breast and Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1239 ◽  
Author(s):  
Abbema ◽  
Vissers ◽  
Vos-Geelen ◽  
Lemmens ◽  
Janssen-Heijnen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Survival Rates ◽  
Relative Survival ◽  
Population Based ◽  
Treatment Patterns ◽  
Entire Study ◽  
Younger Patients ◽  
Risk Of Death ◽  
Over Time

Previous studies showed substantial improvement of survival rates in patients with cancer in the last two decades. However, lower survival rates have been reported for older patients compared to younger patients. In this population-based study, we analyzed treatment patterns and the survival of patients with breast cancer (BC) and colorectal cancer (CRC). Patients with stages I–III BC and CRC and diagnosed between 2003 and 2012 were selected from the Netherlands Cancer Registry (NCR). Trends in treatment modalities were evaluated with the Cochran-Armitage trend test. Trends in five-year overall survival were calculated with the Cox hazard regression model. The Ederer II method was used to calculate the five-year relative survival. The relative excess risk of death (RER) was estimated using a multivariate generalized linear model. During the study period, 98% of BC patients aged <75 years underwent surgery, whereas for patients ≥75 years, rates were 79.3% in 2003 and 66.7% in 2012 (p < 0.001). Most CRC patients underwent surgery irrespective of age or time period, although patients with rectal cancer aged ≥75 years received less surgery or radiotherapy over the entire study period than younger patients. The administration of adjuvant chemotherapy increased over time for CRC and BC patients, except for BC patients aged ≥75 years. The five-year relative survival improved only in younger BC patients (adjusted RER 0.95–0.96 per year), and was lower for older BC patients (adjusted RER 1.00, 95% Confidence Interval (CI) 0.98–1.02, and RER 1.00; 95% CI 0.98–1.01 per year for 65–74 years and ≥75 years, respectively). For CRC patients, the five-year relative survival improved over time for all ages (adjusted RER on average was 0.95 per year). In conclusion, the observed survival trends in BC and CRC patients suggest advances in cancer treatment, but with striking differences in survival between older and younger patients, particularly for BC patients.

AL Amyloidosis and Concomitant Myeloma: Time to Reconsider Assumptions

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4044-4044
Author(s):  
Wesley Witteles ◽  
Ronald Witteles ◽  
Michaela Liedtke ◽  
Sally Arai ◽  
Richard Lafayette ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Plasma Cell ◽  
Research Funding ◽  
Plasma Cells ◽  
Renal Involvement ◽  
World Health ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Bone Marrow Biopsies

Abstract Abstract 4044 Background: Conventionally, multiple myeloma is believed to coexist in approximately 10% of AL amyloidosis patients. However, it is unclear whether this figure is too low based on current World Health Organization criteria. These criteria, mainly created to differentiate myeloma from monoclonal gammopathy of undetermined significance, include the presence of ≥ 10% plasma cells on a bone marrow biopsy or aspirate as being diagnostic of myeloma. Aims: To define the frequency and relevance of a concomitant diagnosis of myeloma in patients with AL amyloidosis. Methods: Records from consecutive patients with biopsy-proven AL amyloidosis treated at the Stanford University Amyloid Center were reviewed. Plasma cell percentages were determined by manual counts from bone marrow aspirate smears and by CD138 immunohistochemistry (IHC) performed on bone marrow core biopsies. Results: A total of 41 patients (median age 61 years, 32% female) were evaluated. The median number of organs involved with amyloidosis was 2 (range 1–4), with 28 patients (68%) having cardiac involvement, 22 patients (54%) having renal involvement, 15 patients (37%) having gastrointestinal involvement, 12 patients (29%) having soft tissue involvement, and 10 patients (24%) having nervous system involvement. All patients had bone marrow biopsies and aspirates performed at the time of amyloid diagnosis, with most undergoing both manual counts of plasma cells from aspirates and IHC from core biopsies. Based on conventional criteria, manual aspirate counts defined 15/28 (54%) patients as having myeloma, and IHC defined 26/31 (84%) patients as having myeloma (p=0.01). Only nine patients had a detectable serum paraprotein on immunofixation (median 1.1 g/dl, range 0.4–2.6). 81% of patients had an elevated serum free light chain (85% lambda), with a median level of 37.3 mg/dl (range 8.6–256 mg/dl). Compared to the frequency of elevated plasma cells, the prevalence of anemia (29%), hypercalcemia (14%), impaired kidney function (21%), and lytic lesions (7%) was low. After a median follow-up of 13 months (range 1–127 months), the one-year overall survival (74% vs. 58%) and three-year overall survival (50% vs. 50%) was not significantly different between patients with ≥10% plasma cells and patients with <10% plasma cells (p=NS). Discussion: As defined by bone marrow plasma cell involvement, a strikingly high percentage (84%) of AL amyloidosis patients would be considered to have concurrent myeloma. This figure is much higher than has been traditionally quoted in the literature, likely due to the utilization of newer methods of counting plasma cells. There was a low prevalence of myeloma-associated end-organ effects (hypercalcemia, anemia, renal insufficiency, lytic bone lesions), and a myeloma diagnosis had no impact on survival. Conclusion: In this cohort of AL amyloid patients, concomitant myeloma was present in the vast majority of patients using modern diagnostic techniques. The significance of this diagnosis appears to be minimal – calling into question whether the diagnostic criteria for myeloma should be redefined in this population. Disclosures: Witteles: Celgene: Research Funding. Liedtke:Celgene: Lecture fee, Research Funding. Schrier:Celgene: Research Funding.

Improved Stem Cell Transplant Related Mortality for AL Amyloidosis At a Single Transplant Center

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2016-2016
Author(s):  
Zandra K. Klippel ◽  
Barry Storer ◽  
William I. Bensinger ◽  
Leona Holmberg ◽  
Pamela S Becker ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Risk Stratification ◽  
Research Funding ◽  
Cardiac Involvement ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Entire Cohort

Abstract Abstract 2016 The role of AHSCT in AL amyloidosis is controversial. There is evidence that AHSCT offers long term disease control with high organ response rates, however, the only randomized phase III trial comparing transplant with conventional melphalan and dexamethasone therapy deemed transplant inferior. Better understanding of risk stratification for SCT candidacy has resulted in TRM rates are as low as 5.6% in some series. The goal of the current study was to evaluate the TRM rate for all consecutive patients who have undergone AHSCT for AL amyloidosis at institution. Special attention in evaluation of any detectable differences in TRM over the time period of this review was a major goal of this project. Retrospective review was performed of all patients with primary AL amyloidosis who have undergone AHSCT at our institution. The database captured patients from December 2001 and our study includes patients through February 2012. Patients who were diagnosed with secondary amyloidosis by the stem cell transplant service and/or referring oncologist were excluded. TRM was defined as death from any cause within 100 days post stem cell infusion. We then evaluated data from the entire cohort and divided it into two different time periods: 2001–2006 and 2007–2012. Thirty-nine patients had an initial AHSCT during the study period. Nine patients were enrolled in the SWOG 0115 trial which comprised tandem autoSCT using 100 mg/m2 of melphalan conditioning 3–6 months apart. Of those, 6/9 (66%) had both transplants. For purposes of this abstract we report on the data resulting from first transplantation only for patients in the SWOG 0115 trial. The median age at transplant for the entire cohort was 57.6 years old (39–74). Males represent 64% of the patients. Most of the patients had symptomatic involvement of one organ (48.7%) with 23% having more than 2 organs involved. There were 14 patients transplanted in the 2001–2006 period and 25 patients in the 2007–2012 period. Overall TRM for 2001–2012 was 5.1%. During the 2001–2006 period TRM was 14% (2/14 patients). No TRM occurred for patients transplanted from 2007–2012. Overall survival (OS) improved when separately comparing the two study periods. Overall survival was 64% at 3 years in the 2001–2006 cohort and 92% at 3 years in the 2007–2012 cohort. Patients in the 2007–2012 cohort include all patients enrolled to SWOG 0115. Sixty percent of patients reported for that period received <200mg/m2 melphalan for transplant conditioning. Eight of nine patients enrolled in SWOG 0115 received 100 mg/m2, one received 140mg/m2. Six patients treated on our institution's standard amylodosis SCT protocol received 140mg/m2 conditioning. The remaining ten patients received 200mg/m2 melphalan. Patients in the 2007–2012 period were more likely to receive induction treatment prior to transplant with novel regimens (72% vs 21% p=0.003). In addition, these patients were more frequently diagnosed with amyloid cardiac involvement. For purposes of this abstract amyloid cardiac involvement is defined according to whether or not the SCT team concluded on the basis of history, physical examination and available ancillary data (including echocardiography) that the patient had amyloidotic cardiac disease (40% vs 14% p=0.15). All patients had echocardiography pre-AHSCT. The mean Inter Ventricular Septum (mIVS) thickness was 14.5 mm in the 2007–2012 period vs. 11.7 mm in the 2001–2006 one p=0.004. Univariate analysis of risk factors affecting improved OS identified year of transplant (>2006; p=0.03), number of treatments pre-transplant (>1; p=0.04), and time from diagnosis to transplant (>4mo; p=0.05) as factors associated with improved survival. Number of organs involved (>1; p=0.06) showed a trend towards worse survival. In conclusion, our single institution data demonstrates a reduction in TRM over the past 5 years. Reasons for improvement in TRM are under investigation and may include better risk stratification, better supportive care (including frequent hospitalization for cardiac monitoring in high-risk patients) and improvement in pre-AHSCT performance status for those patients receiving induction therapy with novel agents. Figure: Comparison of overall survival of patients with AL amyloidosis after autologous stem cell transplant based on year of transplant. Figure:. Comparison of overall survival of patients with AL amyloidosis after autologous stem cell transplant based on year of transplant. Disclosures: Holmberg: Millenium: Research Funding; Otsuka: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Sanofi: Research Funding.

scholarly journals Did the addition of concomitant chemotherapy to radiotherapy improve outcomes in hypopharyngeal cancer? A population-based study

2016 ◽  
Vol 23 (4) ◽  
pp. 266 ◽  
Author(s):  
S.F. Hall ◽  
R. Griffiths
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Treatment Options ◽  
Population Level ◽  
Population Based ◽  
Hypopharyngeal Cancer ◽  
Concurrent Chemotherapy ◽  
Population Based Study ◽  
Clinical Trial Evidence ◽  
Over Time

BackgroundFor oncologists and for patients, no site-specific clinical trial evidence has emerged for the use of concurrent chemotherapy with radiotherapy (ccrt) over radiotherapy (rt) alone for cancer of the hypopharynx (hpc) or for other human papilloma virus–negative head-and-neck cancers.Methods This retrospective population-based cohort study using administrative data compared treatments over time (1990–2000 vs. 2000–2010), treatment outcomes, and outcomes over time in 1333 cases of hpc diagnosed in Ontario between January 1990 and December 2010.Results The incidence of hpc is declining; the use of ccrt that began in 2001 is increasing; and the 3-year overall survival for all patients remains poor at 34.6%. No difference in overall survival was observed in a comparison of patients treated in the decade before ccrt and of patients treated in the decade during the uptake of ccrt.Conclusions The addition of ccrt to the armamentarium of treatment options for oncologists treating head-and neck patients did not improve outcomes for hpc at the population level. 

scholarly journals Epidemiology of Aggressive NK-Cell Leukemia in the United States: A SEER Population-Based Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4537-4537
Author(s):  
Fnu Amisha ◽  
Paras Malik ◽  
Manojna Konda ◽  
Sunilkumar Kakadia ◽  
Tyler Fugere ◽  
...  
Keyword(s):  
Overall Survival ◽  
Nk Cell ◽  
Pacific Islander ◽  
Survival Rates ◽  
The United States ◽  
Population Based ◽  
Population Based Study ◽  
Standard Population ◽  
Poor Outcomes

Abstract INTRODUCTION Aggressive NK-cell leukemia ( ANKL) is a systemic lymphoproliferative disorder of natural killer (NK) cells frequently associated with Epstein-Barr virus (EBV) which has been grouped under histiocytic/dendritic neoplasms in the 2008 WHO classification of hematopoietic neoplasms. Due to rarity of diagnosis, the current available literature is limited to case reports and case series. This population-based study using Surveillance Epidemiology and End result program (SEER) is the largest to explore demographic characteristics, survival patterns and long-term outcomes in patients with ANKL in the United States. MATERIALS AND METHODS We utilized SEER 18 November 2020 submission database to select all patients (&gt; 1 years of age) diagnosed from 2000-2018 with ANKL using International Classification of Diseases for Oncology edition 3 (ICD-O-3) code of 9948/3. Patients were divided into various cohorts based on age (&lt;60 years, 60-79 years, &gt;80 years), sex, race (Caucasians, African American, Asian/Pacific islander and American Indians/Alaska natives) and median household income of county of residence (&lt; $ 50,000 vs &gt; $50,000). We used SEER*stat to calculate age adjusted incidence rate using 2000 US standard population. Kaplan Meier curve was utilized to calculate 5-year overall survival. Cox proportional hazard model was used for multivariate analysis of factors associated with survival and p&lt;0.05 was considered significant. RESULTS A total of 140 patients were identified with ANKL. The median age at diagnosis is 58 years. The crude, age-adjusted to 2000 US standard population and age-specific incidence rate of HCD in Unites states is &lt; 1/100, 000 respectively. The incidence in males is 1.9 times that of females- 92 males (65.7%) and 48 females (34.2%). Between 2001-2018, minimum number of cases were diagnosed in 2010 (n=2).Out of the cohort, 107 patients were White (76.4%), 21 patients were Asian or Pacific islander (15 %), 9 patients were African Americans (6.4%) and 3 patients were American Indian/Alaska native (2.1%). The median overall survival was 7 months (95% CI; 0-16). Survival rates at 1year, 2 years and 5 years were found to be 45.3% , 37.1 % and 31.1% respectively [Figure 1]. 5 year overall survival rates are as follows- Whites ( 69.7% ), Blacks ( 63.1%), American Indian (59.9%), Asian or Pacific Islander ( 66.8%). On multivariate analysis, black race was associated with poor outcomes (p 0.008), whereas sex, income and age had no significant effect on cancer outcomes. CONCLUSIONS Our study shows that ANKL is a rare hematological malignancy in general population with a poor median survival of less than one year. Males are twice more likely to be affected than females with poor outcomes in africo-americans. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Impact of Age and Comorbidity on Multimodal Management and Survival from Colorectal Cancer: A Population-Based Study

2021 ◽  
Vol 10 (8) ◽  
pp. 1751
Author(s):  
Ilmo Kellokumpu ◽  
Matti Kairaluoma ◽  
Jukka-Pekka Mecklin ◽  
Henrik Kellokumpu ◽  
Ville Väyrynen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Rectal Carcinoma ◽  
Population Based ◽  
Population Based Study ◽  
Comorbidity Burden ◽  
Multimodal Management ◽  
The Impact ◽  
Over Time

This retrospective population-based study examined the impact of age and comorbidity burden on multimodal management and survival from colorectal cancer (CRC). From 2000 to 2015, 1479 consecutive patients, who underwent surgical resection for CRC, were reviewed for age-adjusted Charlson comorbidity index (ACCI) including 19 well-defined weighted comorbidities. The impact of ACCI on multimodal management and survival was compared between low (score 0–2), intermediate (score 3) and high ACCI (score ≥ 4) groups. Changes in treatment from 2000 to 2015 were seen next to a major increase of laparoscopic surgery, increased use of adjuvant chemotherapy and an intensified treatment of metastatic disease. Patients with a high ACCI score were, by definition, older and had higher comorbidity. Major elective and emergency resections for colon carcinoma were evenly performed between the ACCI groups, as were laparoscopic and open resections. (Chemo)radiotherapy for rectal carcinoma was less frequently used, and a higher rate of local excisions, and consequently lower rate of major elective resections, was performed in the high ACCI group. Adjuvant chemotherapy and metastasectomy were less frequently used in the ACCI high group. Overall and cancer-specific survival from stage I-III CRC remained stable over time, but survival from stage IV improved. However, the 5-year overall survival from stage I–IV colon and rectal carcinoma was worse in the high ACCI group compared to the low ACCI group. Five-year cancer-specific and disease-free survival rates did not differ significantly by the ACCI. Cox proportional hazard analysis showed that high ACCI was an independent predictor of poor overall survival (p < 0.001). Our results show that despite improvements in multimodal management over time, old age and high comorbidity burden affect the use of adjuvant chemotherapy, preoperative (chemo)radiotherapy and management of metastatic disease, and worsen overall survival from CRC.

scholarly journals Prognostic Relevance of Cytogenetic Chromosomal Abnormalities on Outcome Among AL Amyloidosis Patients in the Netherlands

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2703-2703
Author(s):  
Leonie Abbink ◽  
Mirian Brink ◽  
Wilfried Roeloffzen ◽  
Pino Poddighe ◽  
Monique C. Minnema
Keyword(s):  
The Netherlands ◽  
Plasma Cell ◽  
Prognostic Significance ◽  
Population Based ◽  
Al Amyloidosis ◽  
Population Based Study ◽  
Cytogenetic Abnormalities ◽  
Hematological Response ◽  
Cytogenetic Aberrations ◽  
Igh Rearrangement

Abstract Introduction Systemic light chain (AL) amyloidosis is a clonal plasma cell neoplasm, that carries a poor prognosis. Treatment is adapted from protocols as used in MM, and include bortezomib-based (PI) regimens with or without stem cell transplantation (SCT). PI-based regimens have improved treatment responses and outcomes. Cytogenetic analysis has become an important tool in the diagnostic process of plasma cell disorders, and evidence for prognostic significance of specific genetic abnormalities in relation to therapy efficacy is recognized in systemic AL amyloidosis. Thus far, this prognostic significance has been evaluated in single center institutions. Aim This nationwide, population-based study aimed to assess the impact of cytogenetic abnormalities on hematological response and survival among patients with systemic AL amyloidosis treated with PI-based regimens. Methods We identified 349 patients ≥18 years with systemic AL amyloidosis diagnosed between 2017 and 2019 in the Netherlands Cancer Registry, with survival follow-up until February 1, 2021. Data on therapeutic strategy was known for all individual patients. The cytogenetic aberrations studied include gain(1q), hyperdiploidy, del(17p), and IGH rearrangements, i.e. t(11;14), t(4;14), t(14;16), and t(v;14q32) (non-specified IGH rearrangement). Hematological response and overall survival (OS) were evaluated in relation to cytogenetic aberrations. OS was defined as death by any cause post-diagnosis. Uni- and multivariable analysis for establishing independent predictors of OS, i.e. age, sex, cytogenetic assessment and SCT, was performed using Cox regression. Patients diagnosed at autopsy (n=4), patients who did not start first-line therapy (n=64) or received other therapies (n=37), and patients with systemic AL amyloidosis related to Waldenström Macroglobulinemia (n=10) were excluded. Results In our analytic cohort, 234 patients (median age 67 years; 62% males) were treated with PI-based regimens. Of these patients, 153 (65%) were ≤70 years at diagnosis. SCT was performed in 70 (30%) patients following PI-based regimens. For 170 (73%) patients, cytogenetic assessment was performed. IGH rearrangements were observed in 76 patients (45%), comprised of t(11;14) in 27 patients, t(4;14) in 3 patients, t(14;16) in 2 patients and non-specified IGH rearrangements in 44 patients. Furthermore, 26 patients carried a gain(1q), 4 patients a del(17p), and 33 patients were hyperdiploid. Due to the limited patient number with del(17p), response and OS was not evaluated for this subgroup. A complete remission (CR; n=53), very good partial response (VGPR; n=66), or partial remission (PR; n=55) was accomplished for 74% of the patients, ≥VGPR for 51% of the patients. The reached hematological response was irrespective of the detected cytogenetic abnormalities. In detail, ≥VGPR was 56% for patients with a t(11;14), 62% for patients with a gain(1q), 55% for patients with hyperdiploidy, and 50% for patients with an IGH rearrangement and this was not statistical significant different from patients without these cytogenetic abnormalities. The 3-year OS was 61% for patients treated with PI-based regimens. For patients with a cytogenetic assessment (n=170), there was no significant difference in 3-year OS between patients with or without a t(11;14) (69% vs. 66%, respectively; p=0.70), with or without gain(1q) (57% vs. 68%, respectively; p=0.58), with or without hyperdiploidy (72% vs. 65%, respectively; p=0.63), or with or without an IGH rearrangement (59% vs. 72%; p=0.21). Only SCT was an independent predictor for reduced risk of mortality in uni- and multivariable analyses, overall as well as for the specific cytogenetic subgroups. Conclusion In this Dutch 'real world' population of AL amyloidosis patients treated with PI-based regimens, 74% had a ≥PR and 51% had ≥VGPR. The 3-year OS was 61%. We evaluated the cytogenetic data of 170 patients, but could not confirm a relation between PI-based regimens and outcome, overall as well as in specific cytogenetic subgroups. Patient numbers of the cytogenetic subgroups were low and we could not determine the partner gene in 44 patients with an IGH rearrangement. To the best of our knowledge, this is the first population-based study to evaluate the prognostic relevance of cytogenetic abnormalities in relation to hematological response and OS among systemic AL amyloidosis patients. Disclosures Minnema: Alnylam: Consultancy; Kite/Gilead: Consultancy; Jansen-Cilag: Consultancy; BMS: Honoraria; Celgene: Other: Hospitality.

scholarly journals Ethnicity Matters When Comparing Overall Survival for Patients Diagnosed with Follicular Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1356-1356
Author(s):  
Carolina Velez-Mejia ◽  
Rodolfo Garza Morales ◽  
Qianqian Liu ◽  
Joel E Michalek ◽  
Adolfo Enrique Diaz Duque
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Survival Probability ◽  
Research Funding ◽  
Median Overall Survival ◽  
Population Based ◽  
Statistical Testing ◽  
Wilcoxon Test ◽  
P Value ◽  
Population Based Study

Abstract Background Follicular lymphoma (FLy) is one of the most common subtypes of Non-Hodgkin Lymphomas (NHL) (Cancer EpidemiolPMC4323749). In prior studies, better progression-free survival has been noted in Hispanics (HI), however, further characterization of this ethnic minority needs to be addressed (Ann Lymphoma PMC5877479). This result is consistent with previous research explaining the development of NHL as an heterogeneous process where unique outcomes for races have been noted (Cancer PMID: 22434428). This is the first combined statewide population-based study of Texas (TX) and Florida (FL) evaluating ethnic differences for HI vs Non-Hispanics (NH) comparingdemographics, socioeconomic, clinical and survival patterns of patients diagnosed with FLy. The value of using these states relies on the fact that the percentage of HI in TX and FL are 39.7% and 26.4%, respectively (US Census 2020). Material and Methods This is a retrospective analysis of patients diagnosed with FLy recorded in the Texas Cancer Registry and the Florida Cancer Data System from 2006-2017. Inclusion criteria was histopathologic proven FLy. Patients were divided into HI and NH for comparison. Standard demographic, socioeconomic, clinical, and survival variables were reviewed. All statistical testing was determined using Fisher's Exact test, Pearson's Chi-square test, T-test or Wilcoxon test, as appropriate. Survival time was measured using the day of diagnosis to last date of follow up or death. Survival distribution were calculated based on Kaplan-Meier curves. Results From 2006-2017, 20,497 patients (HI n=3,176, NH n=17,321) were diagnosed with FLy (Table 1, Table 3). In TX, the median age at diagnosis for HI was 60 years (y) vs 64 y for NH [p-value &lt;0.001]. In FL, it was 62 y and 67 y, respectively [p-value &lt;0.001]. In both states, female sex predominated for HI and NH. In TX, the bracket of poverty index that prevailed for HI was 20-100% while for NH was 10-19.9% [p-value &lt;0.001]. In FL, the largest number of HI and NH were in the 10-19.9% bracket [p-value &lt;0.001]. In TX, both HI and NH were more likely be with government-sponsor insurance, however, up to 15% of HI did not have insurance vs 4% in NH [p-value &lt;0.001]. This was also the case in FL, however their number of uninsurance corresponded to 6% and 2% respectively. In TX, the largest number of HI and NH patients were diagnosed at stage III-IV with 49% and 42% respectively [p-value &lt;0.001]. In FL, for these stages it corresponded to 43% and 37% for HI and NH [p-value &lt;0.001]. In TX, treatment at diagnosis showed a similar pattern for HI and NH, choosing mainly no treatment followed by multiple chemotherapy agents [p-value &lt;0.001]. In FL, this trend was also seen. In both states and for HI and NH, most of the patients did not undergo transplant or radiation. In TX, the median overall survival for HI was 9.2 y vs 8.6 y for NH; the survival probability at 2, 5 and 10 y for HI corresponded to 0.835, 0.701 and 0.453, while for NH it was 0.850, 0.703 and 0.354, respectively; and the overall survival probability at 10 y had no statistically significant difference [p-value 0.44] (Table 2, Graph 1). In FL, the median overall survival for HI was not reached vs NH at 10.1 y; the survival probability for HI at 2, 5 and 10 y was 0.871, 0.777 and 0.601, while for NH it was 0.845, 0.709 and 0.506, respectively; and the overall survival probability at 10 y was statistically significant [p-value &lt;0.0001] (Table 4, Graph 2). Conclusions This large two statewide population-based study identified statistical differences in oncological outcomes comparing HI and NH in patients diagnosed with FLy. HI diagnosed with FLy have higher survival at 10 y, and this difference was statistically significant in FL. Moreover, statistical significance was noted in demographic, sociodemographic and disease characteristics. Additional research should be carried out to identify the variables that drive this difference since advance stage, lack of insurance or treatment at diagnosis do not seem to be influencing it. There may be a combination of lifestyle factors (alcohol, cigarette, diet, other), occupational hazards, autoimmune diseases or protective mechanisms, infectious diseases exposures and unique epigenetic interactions that may explain why HI live longer when diagnosed with FLy. Figure 1 Figure 1. Disclosures Diaz Duque: Incyte: Consultancy; Morphosys: Speakers Bureau; Astra Zeneca: Research Funding; Hutchinson Pharmaceuticals: Research Funding; Epizyme: Consultancy; ADCT: Consultancy.

scholarly journals Overall Survival Patterns in Patients with Multiple Myeloma in the Era of Novel Agents and the Role of Initial Clinical Presentation and Comorbidities: A Population-Based Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2136-2136
Author(s):  
Berdien Oortgiesen ◽  
Eric N. van Roon ◽  
Peter Joosten ◽  
Robby Kibbelaar ◽  
Huib Storm ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
The Netherlands ◽  
Research Funding ◽  
Clinical Presentation ◽  
Population Based ◽  
Novel Agents ◽  
Bone Lesions ◽  
Population Based Study ◽  
Asymptomatic Patients

Abstract Introduction Clinical trials have shown improved response rates, progression-free survival and overall survival (OS) in patients with multiple myeloma (MM) when using the novel agents thalidomide, lenalidomide and bortezomib. However, outcome data provided by population-based registries, reflecting real-life, report predominantly improved OS in younger MM patients and only minimal improvement in OS in unselected MM patients older than 65 years. Population-based studies in unselected MM patients in the era of novel agents are relatively limited. Explanations for the marked variation in prognosis across patients may in part be explained by the heterogeneity in the initial clinical presentation, the pre-existing comorbidities, disease biology and response to the therapy. Specific end-organ damage caused by the disease, such as hypercalcemia, renal failure, anemia and bone lesions known as the CRAB symptoms may be associated with worse prognosis in the elderly MM patients. This descriptive prospective population-based cohort study was designed to determine the OS in patients with MM in Friesland, The Netherlands in the era of novel agents, and to analyze the influence of the CRAB symptoms and comorbidities at initial presentation on survival. Methods Since 2005 all patients diagnosed with hematological malignancies in Friesland, a province of the Netherlands, are prospectively registered and followed by their clinicians in a population-based registry, the HemoBase. For this analysis, data on clinical characteristics, comorbidities, treatment and outcome of all patients with newly diagnosed MM in Friesland during the period of January 2005 to January 2013 with a follow-up until January 2014 were retrieved from HemoBase. Supplementary information was obtained from the individual patient hospital records. Both symptomatic and asymptomatic patients were included in the study with subgroup analysis on the symptomatic patients. According to the guidelines from IMWG, each CRAB symptom was divided into two categories (11 mg/dL < serum calcium ≤ 11 mg/dL; 2 mg < creatinine ≤ 2 mg/dL; 10.2 g/d ≤ hemoglobin < 10.2 g/dL and the presence or absence of bone lesions). The patients were divided by age groups (<65, 65 – 75 and ≥75 years old) to illustrate differences in survival in the three age categories. Results From 2005 till 2013 a total of 270 patients were diagnosed with MM in Friesland. The median observation period was 29 months (range 0.26 - 104; IQR 33). Median age was 70 years (range 32 - 92; IQR 15) with a male predominance (60% male). 34, 34 and 32% of patients were < 65 years, 65 - 75 years and ≥ 75 years, respectively. The Charlson Comorbidity Index (CCI) was 0,1 or ≥2 in 60, 22, 18% of patients, respectively. Sixteen percent of patients were asymptomatic. Of symptomatic patients 63% and 27% had CRAB scores of 1-2 and 3-4, respectively. Ten percent of patients had a CRAB score of 0, but were regarded symptomatic by their treating hematologist. Among the symptomatic MM patients 80% received novel agents, 15% other chemotherapy 6% only radiotherapy. The median OS of all patients is 49.5 months, with median OS for symptomatic and asymptomatic patients of 40 and >100 months respectively. Divided into age categories < 65, 65 – 75 and ≥75 years old, the 50% OS is respectively 92, 40 and 29 months (figure 1). For all patients, implementing novel therapies improved OS compared to other therapies (43.5 vs. 21.1 months, hazard ratio (HR) = 1.8, P = 0.017. Patients with a CCI score of 0 have a higher median OS than patients with a score ≥ 2 (HR = 0.6, P = 0.036). Patients with two or more CRAB symptoms have a lower median OS than patients without any CRAB symptoms (HRadjusted = 2.2, P = 0.028). In multivariate analysis, differences in median OS were significant better for patients without hypercalcemia compared to patients with hypercalcemia (HRadj. = 0.6, P = 0.011) and for patients with a serum creatinine ≤ 2 mg/dL vs. ≥ 2 mg/dL (HRadj. = 0.4, P < 0.0001). Conclusion In this population-based study of a complete Dutch cohort of unselected MM patients over the last decade a median OS of 49.5 months was observed. Despite extensive introduction of novel agents increasing age remains an adverse prognostic factor. High comorbidity scores (CCI ≥ 2) and CRAB symptoms, such as hypercalcemia and impaired renal function at initial presentation were significantly correlated with worse median OS. Disclosures Hovenga: Jansen Cilag: Research Funding. Woolthuis:Jansen Cilag: Research Funding. Hoogendoorn:Jansen Cilag: Research Funding.

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