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.

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.

Increased Incidence of Extramedullary Plasmacytomas In Patients with Multiple Myeloma In the Era of Novel Therapy and Effect of Pomalidomide on Extramedullary Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3047-3047
Author(s):  
Kristen Detweiler Short ◽  
S. Vincent Rajkumar ◽  
Francis Buadi ◽  
Dirk Larson ◽  
Suzanne R. Hayman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Soft Tissue ◽  
Research Funding ◽  
Low Dose ◽  
Novel Agents ◽  
Temporal Area ◽  
Immunomodulatory Agents ◽  
Extramedullary Disease ◽  
Extramedullary Plasmacytomas

Abstract Abstract 3047 Background: There is concern about the increased incidence of extramedullary plasmacytomas among patients with multiple myeloma (MM) in recent years (Varettoni et al Annals of Oncology 21: 325–330, 2010). There is controversy about whether novel agents increase the risk of extramedullary disease (EMD). EMD may be associated with decreased overall survival in MM. The purpose of this study was to determine the incidence of true, treatment-emergent EMD in MM among a cohort of patients who have been previously exposed to novel agent (thalidomide, lenalidomide, or bortezomib) therapy, and to evaluate the activity of pomalidomide in patients with EMD. Methods: We examined 174 consecutive patients with relapsed refractory multiple myeloma that were enrolled on a phase II clinical trial of pomalidomide plus low-dose dexamethasone. The study cohort was chosen since all patients had previously been exposed to novel agents, and were followed systematically. We adopted a strict definition of EMD which required that in order to be considered extramedullary, plasmacytomas must not have risen from any bone. Thus, masses arising from the bone with a soft tissue component were not considered extramedullary. Results: Of 174 patients studied, 16 patients (9.2%) had EMD prior to enrollment. In 3 of the 16 patients, EMD was present at time of diagnosis and was therefore not considered as treatment-emergent disease for this analysis. In 13 of 174 patients (7.5%) EMD developed during the course of MM, after starting therapy. All 13 patients by inclusion criteria were exposed to novel agents prior to the onset of EMD, including 100% to immunomodulatory agents (thalidomide or lenalidomide); and 78% (10 patients) were exposed to bortezomib prior to developing EMD. The median number of lines of prior therapy in these patients was 6, range 1–12). EMD occurred a median of 48 months following diagnosis (range, 16–183 months); the rate of EMD in the first 3 years following diagnosis of MM was 3%. Since all patients had prior exposure to immunomodulatory agents in this cohort, we were able to calculate the median length of time from initiation of immunomodulatory agents to onset of EMD as 24 months (range 7–119 months). The EMD sites involved included the temporal area soft tissue (3), muscle (3 [1 pt with 10 different areas of involvement, 1 pt with 5 muscles involved]), chest wall not attached to bone (3), abdominal/pelvic masses (3), kidney (2), scrotum (2), sinus (1), paraspinal (1), hilar/pleural based (1), paraesophageal (1), subcutaneous tissue (1), pancreas (1), spleen (1), mediastinum (1), pleural fluid (1), liver (1). Per protocol, all patients received pomalidomide (2-4 mg per day) and low dose dexamethasone (40 mg once a week). Of the 13 patients, there were 2 CR (with complete disappearance of EMD), 2 PR, 2 stable disease, 3 with progressive disease, and 4 patients who did not have their EMD re-evaluated. Thirty percent (n=4) of patients had a 50% or greater reduction in size of the EMD including one patient who received concomitant radiation. Overall survival from measured from trial entry was significantly shorter for patients who presented with EMD compared to those who did not have EMD, median 16 months versus not reached, p=0.002 (log-rank). Conclusion: We found that 7.5% of patients with relapsed refractory myeloma in the era of novel agents develop EMD during the course of their myeloma, including 3% within 3 years of diagnosis. The underlying reasons for the possible increased incidence of EMD may include better radiographic detection (the role of PET/CT scans and MRI), improved overall survival of patients in recent years, and the possibility that novel agents may increase the risk for strictly defined, true EMD among patients who did not have EMD at time of initial MM diagnosis. These need further study. Disclosures: Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Gertz:Celgene: Honoraria; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

scholarly journals The Impact of Fractures on Survival in Multiple Myeloma: Results from a Population-Based Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4490-4490
Author(s):  
Sigrun Thorsteinsdottir ◽  
Ingigerdur S Sverrisdottir ◽  
Gauti Gislason ◽  
Ola Landgren ◽  
Ingemar Turesson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Cox Regression ◽  
Population Based ◽  
Advisory Committees ◽  
Population Based Study ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Impact

Abstract Introduction Multiple myeloma (MM) causes lytic bone lesions, osteopenia, and fractures, which increase the morbidity of MM patients. Results from small previous studies have indicated that fractures in MM have a negative effect on survival. Aims The aim of the study was to evaluate the impact of fractures on survival in MM patients diagnosed in Sweden in the years 1990-2013. Furthermore, to analyze the effect of bone fractures at MM diagnosis on subsequent survival. Methods Patients diagnosed with MM in 1990-2013 were identified from the Swedish Cancer Registry. Information on date of birth, diagnosis, and death were collected from the Registry of Total Population. Information on all fractures were retrieved from the Swedish Patient Registry. Cox regression model was used with fractures as time-dependent variables. The effect of fractures on survival was assessed for any fracture or a subtype of fracture (a specific bone fracture or ICD-coded pathologic fracture). Either first fracture or the first subtype of fracture was used in the analysis. The effect of a fracture at MM diagnosis (within 30 days before or 30 days after MM diagnosis) on survival was also estimated using a Cox regression model. All models were adjusted for age, sex, time of diagnosis, and previous fractures. Results A total of 14,008 patients were diagnosed with MM in the study period. A total of 4,141 (29.6%) patients developed a fracture including fractures that occurred within a year before MM diagnosis and thereafter. Hereof 2,893 (20.7%) patients developed a fracture after MM diagnosis. The risk of death was significantly increased for patients that developed a fracture after the time of MM diagnosis with a hazard ratio (HR) of 2.00 (95% confidence interval (CI) 1.91-2.10) for all fractures combined. The risk of death was significantly increased for patients that developed all subtypes of fractures after MM diagnosis except ankle fractures. The risk of death was significantly increased for patients that developed pathologic fractures (HR=2.17; 95% CI 2.03-2.32), vertebral fractures (HR=1.73; 95% CI 1.61-1.87), hip fractures (HR=1.99; 95% CI 1.82-2.18), femoral fractures (HR=2.62; 95% CI 2.32-2.98), humerus fractures (HR=2.57; 95% CI 2.32-2.86), forearm fractures (HR=1.24; 95% CI 1.05-1.46), and rib fractures (HR=1.52; 95% CI 1.31-1.77), but not for ankle fractures (HR 1.07; 95% CI 0.79-1.44). A total of 942 (6.7%) of all MM patients were diagnosed with a fracture within 30 days before or 30 days after MM diagnosis. The patients with a fracture at diagnosis were at a significantly increased risk of death compared to those without (HR 1.31; 95% CI 1.21-1.41; Figure) Conclusions Our large population-based study, including over 14,000 patients diagnosed with MM in Sweden in the years 1990-2013, showed that MM patients that developed a fracture after the time of diagnosis were at twofold increased risk of dying compared to MM patients without a fracture. Furthermore, MM patients with a fracture at diagnosis had a 30% higher risk of dying compared to patients without a fracture. Our results indicate that fractures in MM reflect a more advanced disease at diagnosis and stress the importance of managing MM bone disease in all MM patients. Figure. Figure. Disclosures Landgren: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding.

Improved survival among younger but not among older patients with Multiple Myeloma in the Netherlands, a population-based study since 1989

2010 ◽  
Vol 46 (1) ◽  
pp. 160-169 ◽  
Author(s):  
Michael Schaapveld ◽  
Otto Visser ◽  
Sabine Siesling ◽  
Cees G. Schaar ◽  
Sonja Zweegman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
The Netherlands ◽  
Older Patients ◽  
Population Based ◽  
Population Based Study

Analysis of 179 Patients with Newly Diagnosed Multiple Myeloma (MM) Treated with Novel Agents Followed by Autologous Stem Cell Transplantation (ASCT): a Retrospective Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1343-1343
Author(s):  
Joyce Habib ◽  
Neil Dunavin ◽  
Gary Phillips ◽  
Patrick Elder ◽  
Meaghan Tranovich ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Genetic Profile ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Abstract 1343 Background: Multiple myeloma (MM) is the second most common hematological malignancy in the United States with an estimated 20,580 new cases in 2009. Over the past decade, the introduction of novel agents (thalidomide, lenalidomide and bortezomib) have played a pivotal role in improving response rates, duration of response, overall survival (OS) and quality of life. In this study we describe a single center experience with novel agents used for induction followed by high dose chemotherapy (HDT) and first autologous stem cell transplant (ASCT) in patients with MM. Method: A retrospective review of the medical records of 179 newly diagnosed patients with MM seen between October 2006 and December 2009 at The Ohio State University was performed. All patients received novel therapy containing thalidomide, bortezomib or lenalidomide as part of an induction regimen followed by ASCT. All patients received melphalan 140mg/m2 or 200mg/m2 as preparative regimen. Kaplan-Meier estimates were used to plot progression free survival and overall survival. Results: Of the 181 patients seen, 2 were excluded because they did not receive a novel agent as part of induction treatment. Of the 179 patients analyzed, median age was 56.8 years (29-80) with 30% of patients older than 60 years. African American represented 19%. Fifty-nine percent were male, 80% had Durie-Salmon (DS) stage III while 25%, 28%, 18% represented International prognostic score (IPS) stage I, II, and III respectively with 27% unknown. Median comorbidity index score was 2 (2-7) and median Karnofsky performance score (KPS) was 90% (70-100). Thirty percent had high risk genetic profile, and 73% received one line of treatment before ASCT. The median time from diagnosis to ASCT was 8.33 months (4-58). The overall response rate (ORR) prior to transplant was 84% (9% complete (CR), 29% very good partial (VGPR), and 46% partial (PR)). The ORR post ASCT was 89% (CR 45%, VGPR 22%, PR 21%). Non relapse mortality was 1% and 3% at 100 days and 1 year respectively. At a median follow up of 31 months (7-90), 69 patients (38%) had relapsed. Median progression free survival (PFS) was 29 months with 1 and 3 years PFS of 79.3% and 61.5% respectively (Fig. 1). The OS was not reached. One and 3 years OS were 93% and 88% respectively (Fig. 1). Univariate analysis showed that time to transplant > 12 months was associated with poor outcome and decreased overall survival (HR 3.30, p = 0.008). High risk genetic profile was also found to be associated with decreased overall survival although this was not statistically significant (HR 2.31, p = 0.070). Multivariate analysis found that only time to transplant > 12 months was an independent predictor of decreased OS. Significant predictors for disease progression were high risk genetic profile and time to transplant > 12 months in patients receiving 2 or more treatments before ASCT. Conclusion: Induction with novel agents followed by HDT and ASCT improves CR rate, in our case from 9% to 45%. Median PFS (29 months) was comparable to other published data. OS was not been reached after a median follow up of 31 months. Predictors of progression include high risk genetic profile and time to transplant > 12 months. The only significant predictor for survival was time to transplant. Our study suggests that an early transplant may improve OS and PFS. An extended analysis will be presented at the meeting. Disclosures: Phillips: NCI/NIH: Research Funding; NCCM Grant: Research Funding; ARRA RC2 Grant: Research Funding. Byrd:Genzyme Corporation: Research Funding.

scholarly journals Changing trend in mortality rate of multiple myeloma after introduction of novel agents: A population‐based study

2020 ◽  
Vol 147 (11) ◽  
pp. 3102-3109
Author(s):  
Yoshiaki Usui ◽  
Hidemi Ito ◽  
Yuriko Koyanagi ◽  
Akiko Shibata ◽  
Tomohiro Matsuda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Mortality Rate ◽  
Population Based ◽  
Novel Agents ◽  
Population Based Study ◽  
Changing Trend

scholarly journals Decrease in early mortality for newly diagnosed multiple myeloma patients in the Netherlands: a population-based study

2021 ◽  
Vol 11 (11) ◽  
Author(s):  
Mirian Brink ◽  
Kaz Groen ◽  
Pieter Sonneveld ◽  
Monique C. Minnema ◽  
Annemiek Broijl ◽  
...  
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
Multiple Myeloma ◽  
The Netherlands ◽  
Age Groups ◽  
Population Based ◽  
Early Mortality ◽  
Newly Diagnosed ◽  
Population Based Study ◽  
Patients At Risk

AbstractIdentification of risk factors for early mortality (EM) in multiple myeloma (MM) patients may contribute to different therapeutic approaches in patients at risk for EM. This population-based study aimed to assess trends in EM and risk factors for EM among MM patients diagnosed in the Netherlands. All MM patients, newly diagnosed between 1989 and 2018, were identified in the Netherlands Cancer Registry. Patients were categorized into three calendar periods (1989–1998, 1999–2008, 2009–2018) and into five age groups (≤65, 66–70, 71–75, 76–80, >80 years). EM was defined as death by any cause ≤180 days post-diagnosis. We included 28,328 MM patients (median age 70 years; 55% males). EM decreased from 22% for patients diagnosed in 1989–1998 to 13% for patients diagnosed in 2009–2018 (P < 0.01) and this decrease was observed among all age groups. Exact causes of death could not be elucidated. Besides patient’s age, we found that features related to a more aggressive disease presentation, and patient characteristics reflecting patients’ physical condition were predictive of EM. In summary, EM decreased from 1999 onwards. Nevertheless, EM remains high, especially for patients aged >70 years. Therefore, novel strategies should be explored to improve the outcome of patients at risk for EM.

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