scholarly journals Next Generation Sequencing Based Revised International Staging System (R-ISS) for Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2349-2349
Author(s):  
Mark A Fiala ◽  
James Dukeman ◽  
Keith Stockerl-Goldstein ◽  
Michael H. Tomasson ◽  
Tanya M Wildes ◽  
...  
Keyword(s):  
High Risk ◽  
Serum Albumin ◽  
Disease Progression ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Β2 Microglobulin ◽  
Increased Risk ◽  
Risk Of Disease

Abstract Background: The International Staging System (ISS) for multiple myeloma (MM) is a simple risk stratification algorithm based on serum β2-microglobulin and serum albumin that identifies three patient groups with different prognoses. Recently, a revised ISS (R-ISS) has been created that combines ISS stage with serum lactate dehydrogenase (LDH) and chromosomal abnormalities (CAs) identified by fluorescence in situ hybridization (FISH); it has been shown to better stratify patients based on prognosis (Palumbo, et al, J Clin Oncol, 2015). With the increasing availability of deeper sequencing techniques, we sought to determine if the use of next generation sequencing (NGS) instead of FISH for the identification of CAs would further improve the stratification of higher-risk patients. Methods: Data was extracted from the open-access MMRF Researcher Gateway corresponding with interim analysis 8 from the CoMMpass study. The CoMMpass study is enrolling 1000 newly diagnosed MM patients who will be tracked longitudinally for 5 years. CoMMpass collects relevant clinical data as well as sequential tissue samples. Eligibility requirements for CoMMpass include: symptomatic MM with measureable disease by SPEP (≥1.0g/dL), UPEP (≥200mg/24 hours), or SFLC (≥10mg/dL); receiving an immunomodulator (IMID) and/or a proteasome inhibitor (PI) for initial MM treatment; and no prior malignancies in the past 5 years. All sequencing was performed by the Translational Genomics Research Institute (TGEN). CAs were identified using custom software on long-insert whole genome sequencing data. ISS stage was calculated used β2-microglobulin and serum albumin as previously described (Greipp, et al, J Clin Oncol, 2005). R-ISS stage was then calculated as: stage I (ISS stage I, no high-risk CA, and normal LDH); stage III (ISS stage III with high-risk CAs and/or high LDH levels); stage II others. High risk CA were defined as the presence of Del(17p), t(4;14) or (4;16). High LDH was defined as LDH ≥300units/L. We performed a multivariate Cox regression analysis to compare event-free survival (EFS) defined as the interval from diagnosis to disease progression or death controlling for age (>65 vs ≤65 years) and sex for ISS, R-ISS (using FISH data), and R-ISS using NGS data (R-ISS-NGS). The level of significance was set at 0.05 for all tests. Results: 877 patients had β2-microglobulin and serum albumin available and were eligible for analysis. The median age at diagnosis was 64 years, 61% (533) were male, and 76% (666) were white. 34% (296) were ISS stage I, 36% (312) were stage II, and 31% (269) were stage 3. R-ISS was calculated on the 681 patients with available FISH and LDH data. 28% (192) were R-ISS stage I, 61% (417) were stage II, and 11% (72) were stage III. R-ISS-NGS was calculated on the 673 patients with available NGS and LDH data. 32% (212) were R-ISS-NGS stage I, 62% (414) were stage II, and 7% (47) were stage III. ISS stage was significantly associated with EFS; patients with stage II and stage III disease had an 83% (aHR 1.83 [95% CI 1.25-2.69], p = 0.0183) and 171% (aHR 2.71 [95% CI 1.85-3.95], p < 0.0001) increased risk of disease progression or death, respectively, compared to stage I patients. Using R-ISS, the model was able to better stratify patients by risk; patients with stage II and stage III disease had a 111% (aHR 2.11 [95% CI 1.32-3.37], p = 0.0017) and 360% (aHR 4.60 [95% CI 2.58-8.17], p < 0.0001) increased risk of disease progression or death, respectively, compared to stage I patients. Using, R-ISS-NGS the model was able to better stratify patients by risk particularly among stage III patients; patients with stage II and stage III disease had a 125% (aHR 2.25 [95% CI 1.42-3.55], p = 0.0005) and 470% (aHR 5.70 [95% CI 3.12-10.40], p < 0.0001) increased risk of disease progression or death, respectively, compared to stage I patients. Results are summarized in Table 1. Conclusion: R-ISS-NGS improved on FISH based R-ISS stratification, presumably due to more accurate determination of the high-risk CAs of interest. A more thorough analysis including additional candidate CAs may further increase the sensitivity of this NGS based staging system. Table 1 Table 1. Disclosures Vij: Takeda: Consultancy, Research Funding; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Karyopharma: Consultancy; Amgen: Consultancy, Research Funding; Jazz: Consultancy; Shire: Consultancy.

High Risk Status for Stage I Palliation Increases Mortality Following Stage II But Not Stage III

2021 ◽  
Author(s):  
Garrett N. Coyan ◽  
Carlos Diaz-Castrillon ◽  
Mario Castro-Medina ◽  
Luciana Da Fonseca Da Silva ◽  
Melita Viegas ◽  
...  
Keyword(s):  
High Risk ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Risk Status

Clinical Staging for Sleep-Disordered Breathing

2002 ◽  
Vol 127 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Michael Friedman ◽  
Hani Ibrahim ◽  
Lee Bass
Keyword(s):  
Body Mass Index ◽  
Success Rate ◽  
Body Mass ◽  
Sleep Disordered Breathing ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Staging ◽  
Disordered Breathing

OBJECTIVE: The purpose of this study was to identify prognostic indicators that would lead to stratification of patients likely to have successful surgery for sleep-disordered breathing (SDB) versus those destined to fail. STUDY DESIGN: We retrospectively reviewed 134 patients to correlate palate position and tonsil size to the success of the UPPP as based on postoperative polysomnography results. Similar to our previously published data on the Friedman Score as a predictor of the presence and severity of SDB, the palate position was determined on physical examination of the oral cavity and was graded for each patient. This grade combined with tonsil size was used to stage the patients. Stage I was defined as having palate position 1 or 2 combined with tonsil size 3 or 4. Stage II was defined as having palate position 3 or 4 and tonsil size 3 or 4. Stage III patients had palate position 3 or 4 and tonsil size 0, 1, or 2. Any patient with body mass index of greater than 40 was placed in the stage III group. The results of uvulopalatopharyngoplasty (UPPP) were then graded as success or failure and success rates were compared by stage. SETTING: Academically affiliated tertiary care referral center. RESULTS: Stage I patients who underwent UPPP had a success rate of 80.6%, stage II patients had a success rate of 37.9%, and stage III patients had a success rate of 8.1%. CONCLUSION: A clinical staging system for SDB based on palate position, tonsil size, and body mass index is presented. It appears to be a valuable predictor of the success of UPPP. Additional studies and wider use of the staging system will ultimately define its role in the treatment of SDB.

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

Blood ◽  
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.

The effect of gaps in chemotherapy on survival in patients with high-risk stage II and stage III colon cancer.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 180-180
Author(s):  
Yvonne Sada ◽  
Zhigang Duan ◽  
Hashem El-Serag ◽  
Jessica Davila
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Factors ◽  
Stage Iii Colon Cancer ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Multivariable Regression ◽  
The Impact

180 Background: Current guidelines recommend six months of chemotherapy (CT) for stage III colon cancer and consideration for high-risk stage II colon cancer. No previous studies have examined the impact of CT gaps on survival. This retrospective study examines determinants of CT gaps and the effect of gaps on survival. Methods: Using national Surveillance, Epidemiology, and End Results registry-Medicare linked data, high-risk stage II and stage III colon cancer patients diagnosed between 2000-2007 who received surgery and CT were identified. CT duration and gaps were calculated. CT gap was defined as 30 to 90 days between two CT claims. Data on demographics, clinical factors (comorbidity, tumor grade), and treatment factors (time to CT initiation, toxicity, hospitalization) were collected. Multivariable regression was used to examine factors associated with gaps. Cox proportional hazards analysis examined the effect of gaps on risk of mortality. Results: 7,371 patients were identified. Median age was 75 (IQR: 71-79); 47% were male. Among all patients, 1,803 (24%) had a gap. 2,674 patients (36%) received 5 to 7 months of CT, of which 469 (18%) had a gap. Multivariable regression analysis showed that patients who were black (OR 1.3, 95% CI: 1.1-1.7), stage III (1.2, 1.0-1.3), had toxicity (1.3, 1.1-1.4), or had 3 to 4 months of CT (vs. 5-7 months, 2.6, 2.3-3.0) were more likely to have a gap, while patients with a more recent diagnosis in 2007(vs. 2000, 0.6, 0.5-0.8) were less likely to have a gap. 3-year cancer-specific survival was the same in all patients with CT gaps compared with no gaps (80%, 95% CI: 78%-82% vs. 81%, 95% CI: 80%-82%). Cox proportional hazard models showed that patients with gaps did not have increased risk of mortality (HR 0.99, 0.89-1.1) adjusting for patient and clinical factors. Among those who received 5 to 7 months of CT, 3-year survival was 8% lower in patients with gaps compared to those with no gaps (80%, 95% CI: 75%-83% vs. 88%, 95% CI: 87%-90%). Conclusions: Nearly 25% of high-risk stage II and III patients who received CT had a gap. CT gaps were associated with worse survival in patients who received 5 to 7 months of CT. Interventions to improve CT toxicity management and reduce gaps are needed to maximize the benefit of CT.

Serum-based multiplex protein assay for early detection of colorectal cancer and precancerous lesions in a FIT positive population.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16145-e16145
Author(s):  
Herbert A. Fritsche ◽  
Jason Lee Liggett ◽  
Hong Zhang ◽  
Linnea Ferm ◽  
Ib Jarle Christensen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Stage Iv ◽  
Stage I ◽  
Stage Ii ◽  
Supervised Machine Learning ◽  
Stage Iii ◽  
Screening Programs ◽  
Medium Risk ◽  
Validation Set

e16145 Background: Colorectal cancer (CRC) is the second leading cancer worldwide in terms of incidence, 5-year prevalence and mortality for both women and men ages 45 years old and up. The current screening method for many countries with organized screening programs is the FIT test for fecal occult blood; however, this test can result in false positive rates as high as 65%. A FIT reflex test could reduce unnecessary colonoscopies while reducing wait times for those patients that need confirmatory colonoscopies the most. Methods: Danish FIT positive colonoscopy confirmed serum samples (n = 1,499) were divided into training and validation sets maintaining approximately equivalent percentages of clean colonoscopy (40%), low risk adenomas (16%), medium risk adenomas (19%), high risk adenomas (13%), stage I CRC (5%), stage II CRC (2%), stage III CRC (4%), and stage IV CRC (0.5%). Proteins were quantified by custom 16-plex immunoassays utilizing the Luminex xMAP platform. A support vector machine supervised machine learning algorithm was trained with the 16 biomarkers plus age and FIT concentration using 1,291 samples for the outcome medium risk adenoma, high risk adenoma, and CRC. Then this algorithm was tested on a blind 208 sample validation set. Results: The training set was 90% sensitive and 27% specific (AUC = 0.68) and the validation set was 93% sensitive and 21% specific (AUC = 0.63). The sensitivities of the validation by risk/stage was as follows: medium risk adenoma 91%, high risk adenomas 92%, stage I CRC 100%, stage II CRC 100%, stage III CRC 100%, stage IV CRC 93%. Conclusions: This study demonstrates feasibility of a novel blood-based multiplex protein immunoassay for use as a reflex to FIT positive results in population wide screening. It detected nearly all adenomas and carcinomas while reducing FIT false positives and thus unnecessary colonoscopies by more than 20%. A FIT reflex test could alleviate endoscopy burden experienced in countries with organized cancer screening programs, while providing better patient outcomes by detecting polyps and early-stage CRC with high sensitivity.

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

Blood ◽  
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.

scholarly journals Stage II Differentiated Thyroid Cancer Is a High-Risk Disease in Patients <45/55 Years Old

2019 ◽  
Vol 104 (11) ◽  
pp. 4941-4948 ◽  
Author(s):  
Zeming Liu ◽  
Xiaopei Shen ◽  
Rengyun Liu ◽  
Guangwu Zhu ◽  
Tao Huang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mortality Risk ◽  
Older Patients ◽  
Differentiated Thyroid Cancer ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Ajcc Staging System ◽  
Ajcc Staging

Abstract Purpose The mortality risk of stage II differentiated thyroid cancer (DTC) based on the American Joint Committee on Cancer (AJCC) staging system requires further investigation. Methods Retrospective study of DTC in the US Surveillance, Epidemiology, and End Results program for disease-specific mortality risk in various AJCC stages, with patient age stratification of stage II disease. Results Using AJCC staging system 6.0, hazard ratios (HRs) of mortality for stage II DTC in patients &lt;45 yo and patients ≥45 yo and stages III, IVA, IVB, and IVC compared with stage I were 46.95, 4.95, 9.82, 57.37, 222.10, and 468.68, respectively, showing a robustly higher mortality risk in stage II disease in patients &lt;45 yo than in older patients (P &lt; 0.001), comparable with stage IVA (P = 0.482). Similar results were obtained with AJCC 7.0. With AJCC 8.0, HRs of mortality for stage II in patients &lt;55 yo and patients ≥55 yo and stages III, IVA, and IVB compared with stage I were 75.16, 11.23, 69.45, 134.94, and 235.70, respectively, showing a robustly higher risk in stage II disease in patients &lt;55 yo than in older patients (P &lt; 0.001), comparable with stage III (P = 0.57). Kaplan-Meier survival curves displayed a sharp decline with stage II disease in patients &lt;45/55 yo compared with older patients. Conclusions The mortality risk of stage II DTC was sharply differentiated at patient age 45/55 years, being robustly high in younger patients and comparable with stage III/IVA. This emphasizes the importance of considering age when managing stage II DTC and not treating it as a uniformly low-risk disease.

scholarly journals Masaoka-Koga and TNM Staging System in Thymic Epithelial Tumors: Prognostic Comparison and the Role of the Number of Involved Structures

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5254
Author(s):  
Marco Chiappetta ◽  
Filippo Lococo ◽  
Luca Pogliani ◽  
Isabella Sperduti ◽  
Diomira Tabacco ◽  
...  
Keyword(s):  
Staging System ◽  
Tnm Staging ◽  
Multiple Organ ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Thymic Epithelial Tumors ◽  
Epithelial Tumors ◽  
Tnm Staging System ◽  
Staging Systems

Background: The aim of this study was to evaluate the Masaoka–Koga and the tumor node metastases (TNM) staging system in thymic epithelial tumors (TET) considering possible improvements. Methods: We reviewed the data of 379 patients who underwent surgical resection for TET from 1 January 1985 to 1 January 2018, collecting and classifying the pathological report according to the Masaoka–Koga and the TMN system. The number of involved organs was also considered as a possible prognostic factor and integrated in the two staging systems to verify its impact. Results: Considering the Masaoka–Koga system, 5- and 10-year overall survival (5–10YOS) was 96.4% and 88.9% in stage I, 95% and 89.5% in stage II and 85.4% and 72.8% in stage III (p = 0.01), with overlapping in stage I and stage II curves. Considering the TNM system, 5–10YOS was 95.5% and 88.8% in T1, 84.8% and 70.7% in T2 and 88% and 76.3% in T3 (p = 0.02), with overlapping T2–T3 curves. Including the number of involved structures, in Masaoka–Koga stage III, patients with singular involved organs had a 100% and 76.6% vs. 87.7% 5–10YOS, which was 76.6% in patients with multiple organ infiltration. Considering the TNM, T3 patients with singular involved structures presented a 5–10YOS of 100% vs. 62.5% and 37.5% in patients with multiple organ involvement (p = 0.07). Conclusion: The two staging systems present limitations due to overlapping curves in early Masaoka–Koga stages and in advanced T stages for TNM. The addition of the number of involved organs seems to be a promising factor for the prognosis stratification in these patients.

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

Blood ◽  
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 &lt; 0.001), as well for R-ISS stage III versus I (HR, 2.1; P &lt; 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 &lt; 0.001), t(4;14) (HR, 2.06; P &lt; 0.001) and any of the high risk CA (HR, 2.15; P &lt; 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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