Does Race Impact Survival in Multiple Myeloma?

Abstract Purpose: Multiple myeloma (MM), a cancer involving abnormal antibody production from plasma cells, accounts for approximately 1.8% of all new cancer cases in the US. The International Staging System (ISS) for MM classifies patients with serum beta2 microglobulin < 3.5mg/l and serum albumin ≥3.5g/dl as having stage I disease, patients with serum beta2 microglobulin ≥ 5.5 mg/l as having stage III disease, and all others as having stage II disease. The median survival by stage at time of diagnosis is 62 months, 45 months, and 29 months, respectively, for stages I, II, and III. The median age at time of diagnosis of MM is 69 years, with approximately 62% of all patients being at least 65 years old at time of diagnosis. There is a 2-fold increase in MM incidence amongst blacks as compared to whites in both the male and female population. This study was conducted to further characterize our MM patient population and to potentially identify racial and gender impact on mortality. Methods: A retrospective chart review of all patients in our geographic region diagnosed with MM between 2012 and 2017 was conducted using the Louisiana Tumor Registry Board database. Clinical data abstraction included epidemiology, laboratory, and pathologic data at time of diagnosis, and time to autologous stem cell transplant and death, if applicable. We performed chi-square analysis, linear regression, and survival analysis to compare survival outcomes between groups. Results: Chart review data was available for 184 of the 243 patients diagnosed with MM between 2012-2017, including 89 (47.6%) males and 98 females (52.4%), and 90 (48.1%) whites and 88 (47.1%) blacks. Females were significantly older than males (66.1 vs 62.6 years, p=0.037) at time of diagnosis yet whites were not significantly older compared to blacks (65.1 vs. 63.9 years, p=0.498). Among the 108 patients with documented stage of disease, 17 (15.7%) patients were diagnosed with stage I MM compared to 40 patients (37.0%) diagnosed at stage II and 51 (47.2%) diagnosed at stage III. With regards to stage, there was no significant difference between race or sex in our population. When adjusted for gender and age at diagnosis, race was a significant predictor of survival time with survival being 6.45 months shorter for black patients with MM compared to whites with the disease. (95% CI, 1.1 to 11.8; p = 0.019) Conclusion: Our data suggest that race exists as an independent predictor of shorter survival in our black patient population with MM. Additional studies investigating the biologic diversity of this disease are warranted to explain this racial disparity. Disclosures No relevant conflicts of interest to declare.

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The Discriminatory Ability of the R-ISS Is Equivalent to the ISS in a Large Cohort of Newly Diagnosed Multiple Myeloma (NDMM) Patients

Blood ◽

10.1182/blood-2020-136996 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 46-47

Author(s):

Anaïs Schavgoulidze ◽

Valerie Lauwers-Cances ◽

Aurore Perrot ◽

Herve Avet-Loiseau ◽

Jill Corre

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Cox Model ◽

Intensive Treatment ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Discriminatory Ability ◽

Risk Of Death ◽

Significant Difference

Background In the era of personalized treatment in multiple myeloma, high-risk (HR) patients must be defined accurately more than ever. The International Myeloma Working Group (IMWG) recommends to use the Revised International Staging System (R-ISS) to identify HR patients. This score combines ISS, abnormal serum LDH level and 3 high risk chromosomal abnormalities (CA): del(17p), t(4;14) and t(14;16). However, with the advent of new tools in genomics, assessing only 3 abnormalities seems to be limited. Moreover, LDH level is impacted by various medical conditions; its relevance in the score is questionable. Aims The main purpose of our work was to assess the R-ISS on a multi-center cohort of transplant-eligible patients (1180 patients). To our knowledge, this is the first large scale study in Europe. Methods Data were collected from NDMM patients enrolled in 3 clinical trials implemented by the Intergroupe Francophone du Myélome. All patients were eligible to an intensive treatment. The overall survival (OS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method and compared using the stratified log-rank test. The hazard ratio (HR) for progression or death were estimated by a multivariate Cox regression analysis adjusted for age, sex and therapy. Discrimination was assessed by the Harrell's concordance index (C-index) which estimates the proportion of all pairs of patients in whom prediction and outcome are concordant and takes values from 0.5 (no discrimination) to 1.0 (perfect discrimination). Results Altogether, 1180 patients with MM were analysed. Median age of our cohort was 58 years. The majority of patients (78%) received an intensive treatment followed by an autologous stem-cell transplantation (ASCT). Median follow-up was 94 months for OS. Forty-three percent of patients had ISS stage I, 39% had ISS stage II and 18% had ISS stage III. In the multivariable Cox model, the risk of death was increased for ISS stage II versus I (HR, 1.8; P < 0.001), as well for R-ISS stage III versus I (HR, 2.1; P < 0.001). Thirty percent of patients had R-ISS stage I, 62% had R-ISS stage II and 8% had R-ISS stage III. In the multivariable Cox model, the risk of death was 1.8 times higher for R-ISS stage II versus I and 3.0 times higher for R-ISS stage III versus I. Then we compared patients between their couple ISS/R-ISS. Thirty-one percent of the patients from ISS I were upgraded in R-ISS II; 55% of ISS III patients were reclassified in R-ISS II. Patients from the ISS I/R-ISS II couple didn't have a higher risk of progression (HR, 1.02; P = 0.893) or death (HR, 1.36; P = 0.115) than patients in the ISS I/R-ISS I subgroup. We also focused on the patients classified in R-ISS stage II (736 patients). We compared several subgroups: high risk CA (defined by R-ISS) versus standard risk, del(17p) vs. no del(17p), t(4;14) vs. no t(4;14) and high LDH vs. normal LDH. In the multivariable Cox model for OS, the risk of death was increased for patients with del(17p) (HR, 2.14; P < 0.001), t(4;14) (HR, 2.06; P < 0.001) and any of the high risk CA (HR, 2.15; P < 0.001). Conversely, high LDH didn't have an impact neither on PFS (HR, 1.10; P = 0.333) nor OS (HR, 1.09; P = 0.540). Finally, we assessed the performance of the different prognostic models for discriminating patients who progressed from those who didn't (PFS) and patients who died from those who survived (OS) with the Harrell's C-index. The C-index for the R-ISS was the same than the ISS one for both PFS (0.56) and OS (0.61). R-ISS didn't give an additional prognostic value to the ISS. For every models, C-index were the same with or without LDH level; a LDH level upper than the upper limit of normal range didn't bring predictive gain on PFS or OS. C-index was better when we assessed each criteria of the R-ISS independently; this system presents the advantage of considering different prognostic weights and also different associations. Conclusion Our study confirms a significant difference for both PFS and OS between R-ISS stages I, II and III, but importantly, we show that the discriminatory ability of the R-ISS, assessed by the Harrell C-index, is equivalent to the ISS. Moreover, patients in stage R-ISS II have different prognosis depending on their cytogenetic while LDH level doesn't give any difference. Combining ISS, high risk CA and LDH level in only 3 categories induces a loss in the prognosis assessment. A model which assesses all the parameters in an independent way would be better. Figure 1 Disclosures Perrot: Amgen, BMS/Celgene, Janssen, Sanofi, Takeda: Consultancy, Honoraria, Research Funding.

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International Staging System Is Useful for Predicting Survival in Patients with Multiple Myeloma Treated with Chemotherapy ± Interferon vs Intensive Treatment.

Blood ◽

10.1182/blood.v106.11.5177.5177 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5177-5177

Author(s):

Luis Villela ◽

Agustin Avilés-Miranda ◽

Manuel A. López-Hernández ◽

Maria J. Nambo ◽

José R. Borbolla-Escoboza

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Intensive Therapy ◽

Autologous Transplantation ◽

Risk Groups ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Cell Transplant ◽

Intensive Chemotherapy

Abstract The survival of patients with multiple myeloma (MM) varies widely from months to years. This heterogeneity is usually related to the characteristics of the disease and the patient. The identification of the factors which influence the prognosis is very important to predict outcomes, assist in the choice of the treatment and adequately stratify the patients in clinical studies. The Durie-Salmon staging is the classification most used. Recently, the International Myeloma Working Group identified 3 risk groups. They evaluated this system in patients with standard chemotherapy vs. intensive chemotherapy (autologous transplantation) but lacked to mention the paper of interferon (Griepp P. JCO 2005). We analyzed retrospectively 274 patients treated with chemotherapy (CT) ± interferon (INF) or intensive chemotherapy (CT+ autologous transplantation), during a period of 8 year (from 1997 to 2004) and compared overall survival depending of ISS risk groups among different types of treatment. Two hundred and seventy-four patients with the diagnosis of MM within the period of 1997 to 2004 at four Mexican hospitals with available data on albumin and ß2 microglobulin were stratified according to the ISS. A total of 118 patients received chemotherapy [VAD: 104, MEL-PDN: 7, others: 7]; eighty one patients received chemotherapy plus INF as induction (n= 70) or VAD + INF in manteinance (n=11) and 75 received CT + Autologous Stem Cell Transplant (ASCT like intensive therapy) as initial therapy (No tandem transplantations were performed). The survival was estimated using the Kaplan-Meier method with differences in survival examined using the log-rank test. The median age of the patients was 61 years (range: 31– 88), 53% female (n= 146) and 47% male (n=128). Type of MM was: IgG 66 % (n=180), IgA 19% (n=51), light-chains myeloma 13% (n=36), IgD 2% (n=7). Median monoclonal peak was 5.8 g/dL (range: 1.7–13). Whole group (n=274) was in stage I (n=49) with overall survival (OS) of 77.5%, in stage II (n=89) OS 64% and in stage III (n=136), 55.8% (p<0.024). When analyzed patients without INF or ASCT (n=118) the OS was for stage I 56.52%, Stage II 52.5%, Stage III 36.3% (p=0.21). The OS of patients that received INF or ASCT was for stage I 97%, stage II 73%, stage III 69% (p=0.009). The OS for INF group was for stage I 86%, stage II 64%, stage III 48% (p=0.006). When analyzed ASCT vs non-ASCT in whole series with or without INF we found that ASCT is better (90% vs. 56% vs. 46.6%, respectively; p<0.000) This new system of staging for multiple myeloma (ISS) is simple, is based on variables easy to be performed, and it makes it possible to identify different overall survival in patients who were treated with CT ± INF vs. Intensive chemotherapy. As of now, the results in our study group are clearly favorable for patients treated with intensive chemotherapy followed by patients using INF and could be possible modify OS in MM, keeping inmind that our series do not use MEL+PDN as primary treatment.

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Cardiac transthyretin wild-type amyloidosis (ATTRwt): a prospective study of 400 patients followed at the Italian referral center

European Heart Journal ◽

10.1093/ehjci/ehaa946.2144 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P Milani ◽

L Obici ◽

R Mussinelli ◽

M Basset ◽

G Manfrinato ◽

...

Keyword(s):

Natural History ◽

Median Survival ◽

Troponin I ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Wild Type ◽

Staging Systems ◽

Significant Difference ◽

History Of

Abstract Background Cardiac wild type transthyretin (ATTRwt) amyloidosis, formerly known as senile systemic amyloidosis, is an increasingly recognized, progressive, and fatal cardiomyopathy. Two biomarkers staging systems were proposed based on NT-proBNP (in both cases) and troponin or estimated glomerular filtration rate, that are able to predict survival in this population. The availability of novel effective treatments requires large studies to describe the natural history of the disease in different populations. Objective To describe the natural history of the disease in a large, prospective, national series. Methods Starting in 2007, we protocolized data collection in all the patients diagnosed at our center (n=400 up to 7/2019). Results The referrals to our center increased over time: 5 cases (1%) between 2007–2009, 33 (9%) in 2010–2012, 90 (22%) in 2013–2015 and 272 (68%) in 2016–2019. Median age was 76 years [interquartile range (IQR): 71–80 years] and 372 patients (93%) were males. One hundred and seventy-three (43%) had atrial fibrillation, 63 (15%) had a history of ischemic cardiomyopathy and 64 (15%) underwent pacemaker or ICD implantation. NYHA class was I in 58 subjects (16%), II in 225 (63%) and III in 74 (21%). Median NT-proBNP was 3064 ng/L (IQR: 1817–5579 ng/L), troponin I 0.096 ng/mL (IQR: 0.063–0.158 ng/mL), eGFR 62 mL/min (IQR: 50–78 mL/min). Median IVS was 17 mm (IQR: 15–19 mm), PW 16 mm (IQR: 14–18 mm) and EF 53% (IQR: 45–57%). One-hundred and forty-eight subjects (37%) had a concomitant monoclonal component in serum and/or urine and/or an abnormal free light chain ratio. In these patients, the diagnosis was confirmed by immunoelectron microscopy or mass spectrometry. In 252 (63%) the diagnosis was based on bone scintigraphy. DNA analysis for amyloidogenic mutations in transthyretin and apolipoprotein A-I genes was negative in all subjects. The median survival of the whole cohort was 59 months. The Mayo Clinic staging based on NT-proBNP (cutoff: 3000 ng/L) and troponin I (cutoff: 0.1 ng/mL) discriminated 3 different groups [stage I: 131 (35%), stage II: 123 (32%) and stage III: 127 (33%)] with different survival between stage I and II (median 86 vs. 81 months, P=0.04) and between stage II and III (median 81 vs. 62 months, P<0.001). The UK staging system (NT-proBNP 3000 ng/L and eGFR 45 mL/min), discriminated three groups [stage I: 170 (45%), stage II: 165 (43%) and stage III: 45 (12%)] with a significant difference in survival: between stage I and stage II (86 vs. 52 months, P<0.001) and between stage II and stage III (median survival 52 vs. 33 months, P=0.045). Conclusions This is one of the largest series of patients with cardiac ATTRwt reported so far. Referrals and diagnoses increased exponentially in recent years, One-third of patients has a concomitant monoclonal gammopathy and needed tissue typing. Both the current staging systems offered good discrimination of staging and were validated in our independent cohort. Funding Acknowledgement Type of funding source: None

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Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.

Journal of Clinical Oncology ◽

10.1200/jco.1988.6.11.1722 ◽

1988 ◽

Vol 6 (11) ◽

pp. 1722-1727 ◽

Cited By ~ 225

Author(s):

W J Curran ◽

M J Kornstein ◽

J J Brooks ◽

A T Turrisi

Keyword(s):

Relapse Rate ◽

Salvage Therapy ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Subtotal Resection ◽

Total Resection ◽

Mediastinal Irradiation ◽

Significant Difference

To evaluate the role of mediastinal irradiation (RT) following surgery for invasive thymomas, a clinical and pathologic review of 117 patients with the diagnosis of thymoma was completed. Fourteen cases were excluded because of the lack of histologic criteria for a thymic tumor, and the remaining 103 were classified according to a staging system as follows: stage I, completely encapsulated (43); stage II, extension through the capsule or pericapsular fat invasion (21); stage III, invasion of adjacent structures (36); and stage IV, thoracic dissemination or metastases (3). The 5-year actuarial survival and relapse-free survival rates were 67% and 100% for stage I, 86% and 58% for stage II, and 69% and 53% for stage III. No recurrences occurred among stage I patients after total resection without RT. However, eight of 21 patients with invasive (stage II or III) thymomas had mediastinal recurrence as the first site of failure following total resection without RT. The 5-year actuarial mediastinal relapse rate of 53% in this group compares unfavorably with the mediastinal relapse rate seen among stage II or III cases following total resection with RT (0%) or following subtotal resection/biopsy with RT (21%). Despite attempted salvage therapy, five of eight patients with mediastinal relapse following total resection alone died of progressive disease. No significant difference was observed in the local relapse rate, overall relapse rate, or survival between those patients undergoing biopsy and RT v subtotal resection and RT for invasive thymomas (stages II and III). Total resection alone appears to be inadequate therapy resulting in an unacceptably high local failure rate with poor salvage therapy results.

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Serum Levels of OPG and MIP-1α in Untreated Multiple Myeloma Patients. Correlations with Staging, Survival and Bone Disease.

Blood ◽

10.1182/blood.v106.11.5074.5074 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5074-5074

Author(s):

Argyro Papadogiannis ◽

Marie-Cristine Kyrtsonis ◽

Theodoros P. Vassilakopoulos ◽

Tatiana Tzenou ◽

Antonios G. Antoniadis ◽

...

Keyword(s):

Bone Disease ◽

Staging System ◽

Serum Levels ◽

High Serum ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Bone Lesions ◽

Disease Biology ◽

Significant Difference

Abstract Cytokines, such as MIP-1a (macrophage inhibiting factor) and OPG (osteoprotegerin) are assumed to play a role in MM disease biology and bone disease, by mechanisms that are still under investigation. MIP-1a is constitutively secreted by myeloma cells, plays a possible role in the development of MM bone lesions, enhance MM cell adhesion to stromal cells and its serum levels have been recently related to survival in MM. OPG is a soluble decoy receptor which acts as a soluble receptor antagonist that prevents osteoclasts activation and the development of bone disease. Reported findings on serum OPG levels in MM patients are controversial as well as its possible role in the biology of the disease. In order to investigate the possible relationship of MIP-1a and OPG levels in MM patients with prognosis and bone disease, we determined by ELISA serum MIP-1a and OPG levels in 20 MGUS, 82 MM patients and 27 healthy individuals (HI). Both cytokines were determined by ELISA (R&D, Quantikine, USA) in frozen sera collected at dignosis, before treatment. The median age of MM patients was 69 years (44–84) and 50% were males. MM patients’ stage was as follows: 23 stage I, 28 stage II, 31 stage III according to Durie-Salmon staging system and 27 stage I, 17 stage II, 35 stage III according to the International Scoring System (ISS). In HI median MIP-1a was 28 pg/ml (15–54) and median OPG 1600 pg/ml (450–4600). In subjects with MGUS, median MIP-1a was 34 pg/ml (17–58) and median OPG 2300 pg/ml (820–6200). In MM patients, median pretreatment serum MIP-1a was 32 pg/ml (16–100) and OPG 3000 pg/ml (820–25000). No statistical significant difference was observed between HI, MGUS and MM patients with regard to MIP-1a levels but for OPG levels differences between HI and MM patients and between MGUS and MM patients were both significant (0.01 and 0.05 respectively). No relationship was found between MIP-1a or OPG levels and bone disease. However, there was a trend for longer survival in patients with MIP-1a or OPG levels lower than median (5-year overall survival 60 ± 12 vs 38 ± 14, p=0.08 and 66 ± 13 vs 29 ± 13, p=0.07 respectively). In addition MIP-1a levels were correlated with ISS stage: MIP-1a levels were 28.3±11.3 in ISS stage 1, 29.8±11.1 in ISS stage 2, 39±19.2 in ISS stage 3 (p=0.02). In conclusion, in our experience serum OPG levels are higher in MM patients than in MGUS or HI, MIP-1a levels are correlated with the ISS stage and both high serum MIP-1a and OPG levels at diagnosis are related with a shorter survival.

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Personalized Treatment with low doses of Lenalidomide and Dexamethasone for Relapsed Multiple Myeloma in frail or Elderly Patients

Blood ◽

10.1182/blood.v120.21.5049.5049 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5049-5049

Author(s):

Angel Ruedas ◽

Pablo Guisado ◽

Beatriz Aguado ◽

Ricardo Perez ◽

Joaquin Martinez ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Elderly Patients ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Light Chains ◽

Bone Marrow Toxicity ◽

Low Doses ◽

Very Elderly

Abstract Abstract 5049 Background. Treatment of frail or elderly patients with relapsing symptomatic/active Multiple Myeloma (MM) is very difficult due to concomitant diseases, impaired bone marrow reserve, systemic toxicity, relatively decreased renal function and general problems of old age. Dexamethasone and new agents (thalidomide, lenalidomide, bortezomib and bendamustine) have been used in this setting, in most cases with doses adapted to the clinical situation. Aims. To retrospectively analyze the management of frail and/or very elderly MM patients with relapsed and active disease treated with reduced doses of the aforementioned agents in five hospitals in Madrid, Spain. Methods. The files of this group of MM patients were studied. The most common treatment has been the combination of low doses of lenalidomide (len) and of dexamethasone (dex), whereas treatment with reduced doses of other agents has been anecdotal; therefore we analyzed the results of len/dex combinations. Len and dex have been used in lower than standard doses, adapted to the individual initial situation of the patients and tailored according to effect and toxicity throughout treatment. There was no specific protocol and the management of the patients has depended exclusively on the practice and criteria of the treating physicians. Patient risk was stratified following the Salmon and Durie (S&D) score and the International Staging System (ISS). Response was assessed with the IMWG criteria. The study has been approved by the Ethics Committee of Hospital Ramon y Cajal, as coordinating center. Results. 38 patients were included in the study. Mean age was 79 years (range 68–90). 30 pts (79%) were older than 75 years and 10 pts had over 85 years. More than half of the patients (21) had two or more comorbidities. Patients had previously received 1 to 5 (m=1. 8) different treatment modalities, including steroids, melphalan (25), bortezomib (20), thalidomide (6) (or their combinations), and others or even APBSCT (3). 23 pts (60%) had IgG (m=4087 mg/dl, range 868–13000); 13 (34%) IgA (m=2115, range 355–4930) and 2 (5%) only light chains. 22 had κ and 15 λ light chains. 19 (50%) had BJ proteinuria. Mean Hemoglobin level was 10. 7 gr/dl (7. 5–14. 1) and mean creatinine level 1. 3 mg/dl (0. 4–12. 9); 28 (74%) had bone disease. 3 pts had S&D stage I, 22 stage II, and another 13 stage III. 13 pts had ISS stage I, 17 had stage II and 7 stage III. Patients received between 1 and 30 cycles of len/dex (m= 8). Median initial Len dose was 10 mg, the majority between 5 and 15mg, although 4 received 25 mg that were rapidly reduced. Mean initial dex dose was 20mg/day for 4 days. 4 pts (10. 5%) achieved Complete Remission (CR) (3 with negative IF), 27 (71%) Partial Remission (PR) (5 with VGPR) and 2 (5%) a significant, but lesser than 50%, reduction of the M-component (Stable Disease, Std). Altogether, overall response (CR+PR+Std) occurred in 33 pts (86%). The best response occurred after 2 to 9 cycles (m=4) of len/dex. Treatment was stopped in 15 patients due to neurological (4) or hematological (1) toxicity, pulmonary embolism (1), unrelated causes (4) and after achieving a plateau response (5). Time to next treatment was 1–30 months, (m=8 mo). 7 pts relapsed after 3–21 months (m=7). 10 patients died, 5 of related (disease progression, cardiac amyloidosis, renal progression to ESRF) and 5 of unrelated (cancer, sepsis, myocardial infarction, congestive heart failure) causes. Grade III-IV bone marrow toxicity occurred in 9 pts and neurological toxicity (PNP) in 5 (all of them had previously been treated with bortezomib or thalidomide). Conclusions. Personalized low doses of len/dex have been the most common treatment for frail/very elderly patients with relapsed MM in our centers and it is an active and tolerable option in this setting. The haematological toxicity was expectable and manageable, but prior treatments with bortezomib or thalidomide were associated with limiting neurotoxicity. Disclosures: No relevant conflicts of interest to declare.

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Dynamic Changes in International Staging System As a Predictor of Survival Outcome in Patients with Advanced Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-112134 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4438-4438

Author(s):

Jin-Liern Hong ◽

Victoria Crossland ◽

Aaron Galaznik ◽

Paul Dolin

Keyword(s):

Multiple Myeloma ◽

Mortality Rate ◽

Staging System ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Study Cohort ◽

Dynamic Changes ◽

Beta 2 Microglobulin ◽

Line Of Therapy

Abstract Background: The International Staging System (ISS) based on serum beta-2 microglobulin and serum albumin is a useful tool for risk stratification in patients with multiple myeloma. ISS is usually assessed at the time of diagnosis. Recent studies have suggested that risk stratification should be considered dynamic over the disease course. Our study aimed to describe dynamic changes in ISS over time and their impacts on mortality in patients with advanced multiple myeloma. Methods: This study included 417 patients with multiple myeloma from the Flatiron medical records database (Jan 2011- May 2018) who have received at least two lines of therapy and had data on ISS at the time of diagnosis (TDX) and at the time of initiating the second line of therapy (T2L). ISS stage was either abstracted from medical records or derived from the results of laboratory tests of serum beta-2 microglobulin and serum albumin. Patients were followed up from T2L until the earliest event of the last activity in database or death. We calculated mortality rates by TDX and T2L ISS stages, and generated Cox proportional hazard models to estimate the impact of TDX and T2L ISS stages on mortality. Additionally, in the subgroup of patients in ISS stage III at TDX, we used univariate logistic models to identify the predictors for downward shift to ISS stage I or II at T2L. Results: The study cohort had a median age of 70 (interquartile range: 61 to 77), and 59% were male. Based on ISS at TDX, 30%, 37%, and 33% of the study cohort were classified as stage I, II, and III with the mortality rate of 12, 11, and 24 deaths per 100 person-years, respectively. The hazard ratios were 0.95 (95% confidence interval (CI): 0.57-1.61) for patients in stage II and 1.96 (95% CI: 1.22-3.16) for patients in stage III, compared with patients in stage I. Based on ISS at T2L, 47%, 34%, and 20% were classified as stage I, II, and III, with the mortality rate of 7, 19, and 39 deaths per 100 person-years, respectively. The hazard ratios were 2.62 (95% CI: 1.61-4.25) for patients in stage II and 5.18 (95% CI: 3.10-8.64) for patients in stage III, compared with patients in stage I. Dynamic changes in ISS stages over time and mortality rates were depicted in the Table. Among patients in ISS stage I at TDX, about 25% shifted to higher stages at T2L, and had a higher mortality rate (26 per 100 person-years) than did patients remaining in stage I (8 per 100 person-years). For patients in ISS stage II at TDX, 43% stayed in Stage II at T2L, and 46% moved down to Stage I, with a mortality rate of 20 and 5 per 100 person-years, respectively. Among patients in ISS stage III at TDX, 58% moved down to lower stages at T2L. The mortality rate was 10, 21, and 40 per 100 person-years for patients moving down to Stage I and II at T2L and those remaining in Stage III, respectively. In the subgroup of patients in ISS stage III at TDX, strong predictors for shifting down to lower stages were younger age (odds ratio: 2.65; 95% CI:1.20-5.87 for age <65 vs ≥65 years) and serum creatinine ≤ 2 mg/dL at TDX (odds ratio: 2.26; 95% CI:1.03-4.92 for serum creatinine ≤ 2 vs >2 mg/dL), but not gender, race, or cytogenetic abnormality of del17p, t(4;14), and t(14;16). Conclusion: Large changes in ISS stages were observed in multiple myeloma patients when advancing the line of therapy. Changes in ISS stage were also associated with survival outcome. A downward shift to stage I was associated with substantially improved overall survival; in contrast, patients moving up to or remaining in higher stages had poor outcomes, especially for those remaining in ISS stage III. Our results suggest that re-evaluating ISS stage at the time of change in line of therapy can improve prediction of survival outcomes. Disclosures Hong: Takeda Pharmaceuticals International Co.: Employment. Crossland:Takeda Pharmaceuticals International Co.: Employment. Galaznik:Takeda Pharmaceuticals International Co.: Employment. Dolin:Shire: Other: PD holds shares in Shire ; GSK: Other: PD holds shares in GSK; Takeda Pharmaceuticals International Co.: Employment.

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OCD-LIKE DISTAL FEMORAL LESIONS IN CHILDREN WITH BLOUNT DISEASE: WHAT IS THE CLINICAL RELEVANCE?

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967119s00173 ◽

2019 ◽

Vol 7 (3_suppl) ◽

pp. 2325967119S0017

Author(s):

Flo Edobor-Osula ◽

Tamir Bloom ◽

Ciaxia Zhao ◽

Cornelia Wenokor ◽

Sanjeev Sabharwal

Keyword(s):

Femoral Condyle ◽

Medial Femoral Condyle ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Categorical Variables ◽

Plain Radiographs ◽

Significant Difference ◽

Text Figure ◽

Blount Disease

What was the question? The purpose of this study was to evaluate the prevalence of OCD-like lesions around the knee in children with Blount disease. Additionally, we planned to describe the morphologic features of these OCD-like lesions based on plain radiographs and MRI and evaluate any clinical factors that may be associated with such radiologic findings How did you answer the question? After institutional review board approval, the medical records of all patients with a diagnosis of Blount disease (ICD-9 732.4) treated between January 2005 and March 2016 at a single institution were reviewed. All patients included in this study had an initial standing full-length anteroposterior mechanical axis radiograph and anteroposterior and lateral knee radiographs. MRI information was included when available. All patients noted to have an OCD-like lesion on an imaging study (x-ray and/or MRI) were identified and each such MRI was reviewed by three independent examiners, a musculoskeletal radiologist and two pediatric orthopedic surgeons. Each patient’s OCD-like lesion was graded according to two validated staging systems, as described by DiPaola and Hefti. Student t test for comparison of continuous variables and chi -square for categorical variables. Differences were considered statistically significant at p<0.05. What are the results? A total of 68 patients with Blount disease were identified. Five patients were excluded: two due to inadequate imaging, and three patients were adults at initial presentation. Of the 63 remaining patients (87 affected limbs) all had plain radiographs and 37 of these patients (53 limbs) also had an MRI. A total of 9 OCD-like lesions in 6 patients were identified on plain radiographs, with an overall prevalence of 10% (6/63) of patients and 10% (9/87) limbs. From the 37 patients (53 limbs) who had an MRI, 7/37 (19%) patients 10/53 (19% limbs)had the OCD-like lesion present on their MRI. All lesions were found in the posterior one third of the medial femoral condyle. The mean area of the lesion on plain imaging was 197.2 mm 2 (95%CI = 133.9 mm 2, 260.5 mm 2) and 163.0 mm2 (95%CI = 107.6,218.5) on MRI (p=0.36). Based on the Hefti classification there were 3 stage I, 2 stage II and 5 stage III lesions. Using the Dipaola system there were 4 stage I, 4 stage II and 2 stage III lesions. Comparing patients with an OCD-like lesion versus those without, there was no statistically significant difference between the groups in terms of early-onset versus late-onset disease (p=0.21), gender (p=0.23), mean age at imaging (p=.0.06) and laterality (p=0.07). Additionally, there was also no significant difference between the two groups in terms of mean MAD (63.3 mm vs 71.9 mm, p=0.39), mean mLDFA (91.3 degrees vs 89.7 degrees, p=0.43) and mean MPTA (71.7 degrees vs 71.8 degrees, p=0.95). What is your conclusion? OCD-like lesions in the medial femoral condyle can be seen in children with Blount disease. The overall prevalence of these lesions is around 10% based on plain radiographs and 19% based on MRI scans. Based on the numbers available, we were unable to demonstrate any associations between the presence of such OCD-like lesions and the patient’s age, gender or magnitude of varus deformity. Further research is needed to fully ascertain the etiology and natural history of these lesions in children with Blount disease. [Table: see text][Figure: see text][Figure: see text]

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Tailored Low Dose Lenalidomide with Low Dose Dexamethasone (len/dex) in Previously Treated Patients with Multiple Myeloma Older Than 70 Years Requiring Treatment.

Blood ◽

10.1182/blood.v114.22.4950.4950 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4950-4950

Author(s):

Angel Ruedas ◽

Ricardo Perez ◽

Valentin Garcia ◽

Alicia Smucler ◽

Pilar Bravo ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Elderly Patients ◽

Low Dose ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Bone Marrow Toxicity ◽

Low Doses ◽

Previously Treated

Abstract Abstract 4950 Background & Aims The management of elderly patients with Multiple Myeloma (MM) previously treated requiring further therapy (although in most cases palliative) is very difficult due to the presence of concomitant diseases, decreased bone marrow reserve, systemic toxicity, relatively decreased renal function and general problems of old age. As in this setting the tolerability of standard doses of conventional chemotherapy, high doses of dexamethasone or IMiDs is a concern, we report the preliminary results of the combination of tailored low doses of lenalidomide (len) and low doses of dexamethasone (dex). Methods We retrospective analyze the results of the combination of low dose lenalidomide and low dose of dexamethasone (len/dex) in 14 patients aged over 70 years with pretreated MM and progressive disease. Low doses of len (5-10 mg daily for 21days) were initially given and flexibly modified in subsequent cycles according to response and toxicity, along with low doses of dex (20-40 mg/day for 4 days) in most (12) patients. G-CSF and red cell transfusions were used when needed. Patient risk was stratified following the Salmon and Durie (S&D) score and the International Staging System (ISS). Response was assessed with the IMWG criteria. Results Median age was 80 years (70-90). All patients had received between 2-5 different previous modality treatments (m=2), including bortezomib (7), thalidomide (4) or PBSCT (2). 11 pts had IgG, m=3397mg/dl (868-4990), 2 IgA m=1460 (1050-1870) and another one BJ. 9 pts had κ and 4 » light chains. Median Hemoglobin level was 10 gr/dl (7.2-11.4) and median creatinine level 1.19 mg/dl (0.75-1.63). 11 (78%) had bone disease. 9 pts had S&D stage II, 4 stage III and another one stage I. 7 pts had ISS stage II, 4 had stage I and 2 stage III. Patients received between 2 and 13 cycles of len/dex (m=6.8). 11 pts (78%) achieved Partial Remission (PR) and 2 (14%) achieved significant, but lesser that 50%, reduction of the M-component (Stable Disease: Std). Overall response (PR+Std) occurred in 13/14 patients (92.8%). The best response occurred between 2-12 cycles of len/dex. Grade III-IV bone marrow toxicity occurred in 5 pts (35 %) and neurological toxicity (PNP) in 5 pts (35%) (all of them had received previous bortezomib or thalidomide). Treatment was stopped in 6 pts: for unrelated causes (1), due to neurological (3) or haematological (1) toxicity and in 2 pts after achieving Std and both relapsed after 3 months. Conclusions Treatment with tailored low doses of lenalidomide and low doses of dexamethasone (len/dex) is an active and tolerable option for previously treated elderly patients with symptomatic MM. Low lenalidomide doses can be flexibly modified according to the quality of the response and the hematological toxicity that is expectable and manageable. Previous treatments with bortezomib or thalidomide is associated with neurotoxicity. Disclosures No relevant conflicts of interest to declare.

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Preoperative tumor markers at diagnosis in women with malignant mixed müllerian tumors/carcinosarcoma of the uterus

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2007.01187.x ◽

2008 ◽

Vol 18 (6) ◽

pp. 1200-1201 ◽

Cited By ~ 3

Author(s):

P. J. Hoskins ◽

N. Le

Keyword(s):

Endometrial Cancer ◽

Tumor Markers ◽

Chart Review ◽

Stage Iv ◽

Retrospective Chart Review ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Upper Limit ◽

Stage Stage

CA125 is a well-recognized marker for endometrial cancer. Uterine malignant mixed müllerian tumors (MMMTs) are increasingly being recognized as an aggressive adenocarcinoma, not a sarcoma. There are no data in the literature regarding CA125 in this malignancy. One hundred twelve women with surgically staged MMMT, diagnosed between July 1990 and September 2005, had a retrospective chart review performed. Preoperative CA125 levels were available in 29 (26%) women. Seventeen (49%) women had levels above the upper limit of normal of 35 kμ/L. Mean levels increased with increasing surgical stage: stage I 53.4 kμ/L; stage II 122.5 kμ/L; stage III 147.1 kμ/L; and stage IV 428.4 kμ/L. Elevated levels of CA19-9, CEA, and CA15-3 were found in 8%, 12%, and 25%, respectively.

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