scholarly journals Association between Immunoglobulin Isotypes and Cytogenetic Risk Groups in Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5585-5585
Author(s):  
Ramya Muddasani ◽  
Albert Ho ◽  
Meredith Akerman ◽  
Shahidul Islam ◽  
Mitchel Polak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Group ◽  
Clonal Evolution ◽  
Prognostic Significance ◽  
Risk Groups ◽  
Categorical Variables ◽  
Intermediate Risk ◽  
Immunoglobulin Isotypes ◽  
Standard Risk

Abstract Introduction: Cytogenetic abnormalities (CAs) in multiple myeloma (MM) have prognostic significance and predict the risk of clonal evolution, disease progression, and response to treatment. The Revised International Scoring System (R-ISS) was recently updated to incorporate high risk CAs, including del(17p), t(14:16), and t(14:20), the presence of which confer a poorer prognosis. Prior studies have demonstrated the prognostic value of specific CAs and MM immunoglobulin isotypes, for example, non-IgG isotypes having been associated with poorer prognosis. However, data showing a link between cytogenetic risk groups and MM isotypes are limited. Thus, we determined whether a relationship exists between higher-risk CAs and MM isotypes, as well as the degree of malignant plasma cell infiltration of the bone marrow (BM). Methods: We performed a retrospective analysis of a multi-institutional commercial pathology repository of 442 MM patients identified according to the International Myeloma Working Group criteria that included assessment of BM infiltration (BM%), MM isotype, CA, and cytogenetic risk group. The study protocol was approved in accordance with IRB standards. As per the R-ISS, the high risk CAs included del(17p), t(14:16), and t(14:20), intermediate risk CAs included t(4;14), del(13q), dup(1q), and hypodiploidy, and standard risk CAs included t(6;14), t(11;14), and hyperdiploidy. Patients with CAs that included more than one risk group were considered to be in the higher risk category. Associations between categorical variables were made using the chi-squared test or Fisher's exact test. The Mann-Whitney test was used to compare groups (MM isoytpe, CAs, or cytogenetic risk group). Statistical significance was considered at p<0.05. Analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC). Results: Among the 442 MM patients, isotype groups included 42% IgG, 16% IgA and 42% light chain-only (LCO). There were 184 patients (42%) who had CAs associated with known MM cytogenetic risk groups, of which 34% were standard-risk, 61% were intermediate-risk, and 5% were high-risk. The median BM% of clonal plasma cells was 50% (range 1-95%). When examining the relationship between any CA and BM%, del(13q14), dup(1p32), dup(1q21), t(4;14), trisomy(11q13), and monosomy(16q23) were associated with a significantly higher BM% than patients who were lacking those respective CAs. For example, the median BM% for patients with t(4;14) was 60% compared with 15% in patients lacking this translocation (p<0.0001). LCO isotype was associated with a lower BM% (p<0.04), however there was no significant correlation between IgG/IgA isotypes and BM%. There was a higher median BM% seen in the intermediate risk group (50%, p<0.0001) compared to standard risk group (20%, p<0.04). The high risk group was not significantly associated with BM%. When comparing isotypes to cytogenetic risk groups, IgA isotype was significantly associated with intermediate risk cytogenetics (p<0.03). Conversely, there was a significantly lower rate of standard risk CAs among IgA isotypes (p<0.01). There was no significant correlation between IgG/LCO and cytogenetic risk. IgA isotype correlated with specific CAs, including del(13q) (p<0.02) and del(16q23) (p<0.04). There was a higher rate of t(11:14) in the non-IgA isotype groups. Additionally, IgG isotype was associated with a trisomy(11q13) (p<0.03). LCO isotype also corresponded with a higher rate of del(17p) (p<0.03), t(11:14) (p<0.03), and a lower rate of t(4:14) (p<0.04) and trisomy (11q13) (p<0.01). Conclusions: In MM, CAs are valuable in risk stratifying patients and predicting treatment responses. In this study, data suggest that the IgA isotype is significantly associated with intermediate-risk cytogenetics, including del(13q) and hypodiploidy, and LCO disease correlates with high risk cytogenetics, including del(17p). When taken together this may explain the previously known association of these isotypes with poorer prognosis, and suggests divergent clonal evolution among MM isotypes. Associations between clinical parameters and disease responses remain ongoing. Disclosures No relevant conflicts of interest to declare.

Association between immunoglobulin isotypes and cytogenetic risk groups in multiple myeloma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19510-e19510
Author(s):  
Ramya Muddasani ◽  
Angela Ramdhanny ◽  
Gabriel Lutz ◽  
Meredith Akerman ◽  
Albert Ho ◽  
...  
Keyword(s):  
Renal Failure ◽  
Light Chain ◽  
Risk Group ◽  
Risk Groups ◽  
Organ Damage ◽  
Categorical Variables ◽  
End Organ Damage ◽  
Immunoglobulin Isotypes ◽  
Lytic Lesions ◽  
Standard Risk

e19510 Background: Cytogenetic abnormalities (CA) carry prognostic significance in MM. Immunoglobulin isotypes also predict disease behavior, with non-IgG subtypes historically being associated with poorer outcomes. We hypothesized that MM non-IgG isotype and higher risk CA are associated with greater degree of marrow infiltration (BM%) and presence of end organ damage at presentation. Methods: 552 MM patients were retrospectively analyzed using a multi-institution repository of BM%, isotype, and CA risk groups stratified by mSMART criteria. A subset of 110 patients were used to assess clinical comparisons and associations between CA, isotype, and end organ damage using the chi-square or Fisher’s exact test for categorical variables and the Mann-Whitney test to compare between groups for continuous variables. Results: There was a higher BM% seen in the intermediate risk group compared to standard risk group (50% vs 20%, p < 0.04). A lower BM% was seen in the IgG subtype compared to other isotypes (27% vs 45%, p < 0.02). CA including del(13q), del(16q), dup(1p), dup(1q), t(4;14), t(11;14), and trisomy 11 were associated with a higher BM%. When comparing isotypes to CA risk groups, IgA isotype was associated with greater risk, including del(13q) and del(16q). IgG isotype was associated with trisomy 11, while light chain MM correlated with higher risk CA including del(17p), and dup(1q). Lytic lesions on presentation were more frequent in patients with trisomy 11 and less frequently in IgA MM. Anemia presented more in IgA MM, and renal failure in patients with t(14;16). Conclusions: Lower BM% was found in IgG isotype MM, which correlated with standard risk CA, whereas light chain MM was associated with higher risk CA; this risk group being more likely to present with renal failure. Unexpectedly, lytic lesions on presentation correlated with non-IgA isotype and better risk CA. Further studies are needed to confirm these findings prospectively to determine if they can predict end organ damage in patients with specific isotypes or CA groups.

Cytogenetic Progression in Patients with Multiple Myeloma As Assessed By Serial Bone Marrow Biopsy Is Associated with Worse Outcome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4209-4209
Author(s):  
Catherine Randall Paschal ◽  
Jens C Eickhoff ◽  
Aric C Hall ◽  
Jennifer Laffin ◽  
Natalie Scott Callander ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
High Risk ◽  
Risk Group ◽  
Clonal Evolution ◽  
Intermediate Risk ◽  
Disease Course ◽  
Cytogenetic Abnormalities ◽  
Standard Risk

Abstract Background:Multiple Myeloma (MM) is a hematologic malignancy characterized by the proliferation of clonal, mutated plasma cells, which ultimately leads to multi-organ damage and in most cases death. Despite improved treatments, clinical heterogeneity remains, with some patients succumbing to disease within 1-2 years. Certain cytogenetic and FISH abnormalities at diagnosis confer a higher likelihood of poor outcomes (Mikhael et al., 2013). Still, the utility of repeated cytogenetic assessment over the course of disease is unknown. Methods: We performed a retrospective review to identify MM patients with cytogenetics (CG) performed at diagnosis who had two or more bone marrow (BM) examinations performed during follow up over a five year period at UW Carbone Cancer Center. We reviewed the pathology and CG results from each BM sample. CG data was categorized into risk groups using the mSMART stratification criteria: High risk - deletion 17p13, t(14;16), t(14;20); intermediate risk - t(4;14), hypodiploid, deletion 13, gain of 1q21; standard risk - hyperdiploidy and all other abnormalities, and normal CG. CG progression over disease course was categorized based on stability or change in CG risk group. We measured survival from date of diagnosis to death or last follow up. Results: 130 patients with CG at diagnosis were identified over the five year period of the study. These patients had 365 follow-up bone marrow (BM) aspirates, 341 with repeat CG study. Initial cytogenetics were as follows: 90 (69%) of 130 patients had normal CG at diagnosis, 13 (10%) standard risk CG, 16 (13%) intermediate risk CG, and 11 (8%) high risk CG. Serial CG studies showed both development of new CG abnormalities in patients with previously normal studies, and clonal evolution with CG abnormal patients acquiring additional abnormalities on repeat testing. 24 (27%) of 90 patients with normal CG at diagnosis developed abnormal CG during disease course: 12 had intermediate risk CG and 9 high risk CG, the latter all due to p53 deletion. Clonal evolution and drift among initially CG abnormal patients were also common. Of the 34 patients with abnormal CG results on diagnosis and subsequent bone marrow samples, clonal evolution was identified in 19 patients (56%) and 4 (12%) patients developed new CG abnormalities unrelated to the prior clone, while 11 (32%) showed stable CG. Despite this high rate of change, only two patients with abnormal CG at diagnosis moved from a lower to a higher cytogenetic risk group. When we correlated CG at diagnosis with survival, we found that patients with high risk CG at diagnosis appeared to have shorter median overall survival at 3.8 yrs (range 1-12 yrs) compared with 7.4 yrs (range 2-12 yrs) for intermediate risk, 8.5 yrs (range 2-9 yrs) for standard risk, and 8.2 yrs (range 1-12 yrs) for normal CG. Comparison among all four groups was not statistically significant however, possibly due to the small proportion of high risk CG patients. When we examined the effect of acquiring CG abnormalities, we found that development of abnormal CG in patients with normal CG at diagnosis was associated with shorter median OS (4.0 yrs) compared to either persistent normal CG (11.3 yrs) or any CG abnormality at diagnosis (7.4 yrs), overall comparison p = 0.0048. Conclusion: Our longitudinal study of 130 unselected patients with MM revealed a cohort who showed cytogenetic progression. In patients with normal CG at diagnosis, the presence of cytogenetic abnormalities in follow-up BM specimens was associated with inferior overall survival. This finding indicates that serial testing may facilitate the detection of a higher risk patient cohort. Further analysis is underway to identify clinical parameters that underlie a higher risk of clonal evolution or development of new cytogenetic abnormalities. The results of our study will help elucidate the optimal prognostic utility of cytogenetic analysis in patient care. Disclosures No relevant conflicts of interest to declare.

The Impact of Genetic Abnormalities (GA) and Other Factors on Survival in Patients after 65 Years with Multiple Myeloma (MM)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5314-5314
Author(s):  
Andrei Garifullin ◽  
Irina Martynkevich ◽  
Sergei Voloshin ◽  
Alexei Kuvshinov ◽  
Ludmila Martynenko ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
High Risk ◽  
Risk Group ◽  
Fish Analysis ◽  
Intermediate Risk ◽  
Old Patients ◽  
Genetic Abnormalities ◽  
The Impact ◽  
Standard Risk

Abstract Background. The increase of life expectancy in patients after 65 years with MM is the main aim of treatment. Lack of carrying out aggressive anti-multiple myeloma therapy increase influence of different factors on OS. Aims. To compare influence GA and other different factors on overall survival in 65 and more years old patients with MM. Methods. We retrospectively analyzed 40 patients 65 and more years (median age 71 years, range 65-86; male/female - 1:1.35). The incidences of genetic abnormalities were determined in all cases. Cytogenetic analysis was performed on bone marrow samples using standard GTG-method. Metaphase FISH analysis was performed according to the manufacturer's protocol using DNA probes: LSI 13(RB1)13q14, IGH/CCND1, IGH/FGFR3, LSI TP53 (17q13.1). Stratification of patients was carried in groups of risk according to the modified molecular classification mSMARTmod 1.0 and mSMARTmod 2.0. Patients with 2 and more chromosomal aberrations were additionally entered in high-risk group of both systems. Results. GA in multiple myeloma after 65 years old patients were detected in 22.8% (9/40). The occurrence frequency of t(11;14) was 26.0% (6/23), del(13q) - 20.8% (5/24), t(4;14) - 4.3% (n=1/23), del(17p) - 0% (n=0/11). 33/40 (82.5%) patients entered into standard risk group, 4/40 (10%) - into intermediate risk, 3/40 (7,5%) - into high-risk. Median OS (MOS) according to mSMARTmod 1.0 in standard risk group (33/40) was 78 months, in high-risk (7/40) - 54 months. Median OS according to mSMARTmod 2.0 in standard risk group (33/40) was 78 months, in intermediate-risk (4/40) - 56 months, in high-risk (3/40) - 49 months. In patients groups without renal failure (35/40) MOS was 78 vs. 46 months with renal failure (5/40). MOS isn't reached in patients with ISS I (4/27), but MOS in patients with ISS II (13/27) and ISS III (10/27) were 50 and 54 months, respectively. MOS in patients group (10/40), who have both (bortezomib and lenolidomide) anti-myeloma agents was 110 months vs. 57 months in group (30/40) only with bortezomib-based regimen of treatment. Conclusions. Many factors influence on OS in 65 and more years old patients with MM. However, patients, who had treatment with bortezomib and lenelidomide had the best results of OS. Disclosures No relevant conflicts of interest to declare.

scholarly journals Association between Clinical Presentation of Multiple Myeloma, Immunoglobulin Isotypes, and Cytogenetic Risk Groups

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Ramya Muddasani ◽  
Angela Ramdhanny ◽  
Gabriel Lutz ◽  
Albert Ho ◽  
Meredith Akerman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
High Risk ◽  
Board Of Directors ◽  
Clinical Presentation ◽  
Risk Groups ◽  
Organ Damage ◽  
Intermediate Risk ◽  
Advisory Committees ◽  
Immunoglobulin Isotypes

Introduction: In multiple myeloma (MM), chromosomal abnormalities (CAs) are valuable in risk stratifying patients and predicting disease free survival. While immunoglobulin isotypes have historically contributed to MM staging, more recently established classifications of CAs have allowed for a revised staging system that better predicts disease behavior. In this retrospective study, we hypothesized that CAs correlate with disease characteristics including immunoglobulin heavy chain isotype, degree of bone marrow infiltration (PC%), and end-organ damage. Methods: MM patients diagnosed between 2013 to 2019 were included in this retrospective chart review using electronic records from two distinct sources: (1) 442 patients from an independent pathology database and (2) a validation cohort composed of 110 patients from our institution. CAs were stratified by Mayo mSMART 2.0 criteria into standard, intermediate, and high-risk groups (Mikhael et al. Mayo Clin Proc 2013). End-organ damage was defined as the presence of lytic bone lesions, anemia, hypercalcemia, or renal failure on clinical presentation. Within each cohort, associations between categorical variables were made using the chi-squared test or Fisher's exact test, as deemed appropriate. The Mann-Whitney test was used to compare between groups for continuous variables. A result was considered statistically significant at the p&lt;0.05 level of significance. All analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC). Results: 552 MM patients were included in the study. Multi-variate analysis revealed that del(13q14), dup(1q21), t(4;14), trisomy (11q13), del(16q23), and hypodiploidy were associated with a significantly higher PC%, whereas kappa light chain only (LCO) disease was associated with a lower PC%. Higher median PC% was found when comparing the intermediate to standard CA risk group. IgA isotype was associated with intermediate risk CAs including del(13q) and standard risk CAs including t(11;14), while IgG isotype was associated with dup(1q21), and kappa LCO disease correlated with a higher rate of higher risk CAs including deletion of p53 at 17p13 and dup(1q21). With regard to clinical presentation, lytic lesions were more frequent in patients with normal cytogenetics and trisomy 11 and less frequent in IgA isotype, whereas the presence of anemia on presentation correlated with IgA isotype. Renal failure was associated with MAF translocations including t(14;16), a high-risk CA. Conclusions: We demonstrate that a relationship exists between specific CAs, immunoglobulin isotypes, and clinical presentations in MM. Our data indicate that IgA isotype is significantly associated with intermediate-risk cytogenetics including del(13q) and anemia on presentation, and that light chain disease and renal failure correlate with high risk CAs including del(17p13). These associations between biological and clinical features further support the concept of divergent cytogenetic evolution in MM as being an underlying factor leading to distinctive disease presentations. Disclosures Braunstein: Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Preliminary Report of Risk-Based Approach in Korean Patients with Newly Diagnosed Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4911-4911 ◽  
Author(s):  
Soo-Mee Bang ◽  
Jae Hoon Lee ◽  
Sung-Soo Yoon ◽  
Seonyang Park ◽  
Je-Jung Lee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
Chromosome 13 ◽  
Beta 2 ◽  
The Impact

Abstract Purpose: The purpose of this study was to examine the impact of different approaches stratified on risk based on chromosome 13 deletion and serum beta-2 microglobulin (MG) level would lead to survival benefit in patients with newly-diagnosed multiple myeloma. Patients and Methods: At diagnosis, fresh marrow samples for FISH and serum for beta-2 MG were sent to central laboratory and reviewed. Patients who had chromosome 13 deletion and high beta-2 MG (&gt;2.5 mg/L) were considered to have high-risk disease. Patients without chromosome 13 deletion and low beta-2 MG were classified as low-risk group. Intermediate-risk group had to have either one of these two risk factors. After VAD induction chemotherapy, autologous stem cell transplantation conditioned with MEL200 was performed in patients at high- and intermediate-risk. DECP consolidation chemotherapy was added for high-risk patients. Patients who achieved CR after VAD in low-risk did not receive any further treatment. Results: As of Jun 2004, 50 patients were registered from 10 centers. Median age was 58 (range, 39–68) years old. Chromosome 13 deletion was detected in 18 patients (36%) and beta-2 MG was elevated in 39 patients (78%). Thirteen patients were classified as high-risk, 31 patients as intermediate-risk and 6 patients as low-risk. After median follow-up of 9 months, progression-free and overall survival at 1-year were 56% and 76%, respectively. To date, no statistically significant differences in survival were observed between risk groups (figure 1). Conclusion: In this study, risk-based approach in patients with multiple myeloma appeared to be feasible. Study accrual is ongoing and updated results will be presented. Figure Figure

A Novel Risk Classification Model Predicts Overall Survival and Locoregional Surgery Benefit in Colorectal Patients with Distant Metastasis at the Initial Diagnosis

2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Risk Classification ◽  
Low Risk ◽  
Classification Model ◽  
Intermediate Risk

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.

scholarly journals Induction chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in the treatment of different risk locoregionally advanced nasopharyngeal carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592092821
Author(s):  
Li-Ting Liu ◽  
Yu-Jing Liang ◽  
Shan-Shan Guo ◽  
Hao-Yuan Mo ◽  
Ling Guo ◽  
...  
Keyword(s):  
High Risk ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
Risk Group ◽  
Risk Groups ◽  
Rank Test ◽  
Intermediate Risk ◽  
Free Survival ◽  
Alternative Treatment Strategy

Background: This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 1814 eligible patients with stage II–IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method, and the differences were compared using the log-rank test. Results: Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups ( p = 0.040). Conclusion: IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

The Frequency of Genetic Anomalies According to Clonal Plasma Cells' Phenotype in Patients with Newly Diagnosed (ND) Multiple Myeloma (MM)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5316-5316
Author(s):  
Andrei Garifullin ◽  
Irina Martynkevich ◽  
Sergei Voloshin ◽  
Alexei Kuvshinov ◽  
Ludmila Martynenko ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
Risk Groups ◽  
Fish Analysis ◽  
Newly Diagnosed ◽  
Definition Of ◽  
Standard Risk

Abstract Background. Genetic anomalies (GA) are primary link of pathogenesis in MM. GA lead to formation of clonal plasma cells, which has different phenotype. Aim. To estimate the incidence of GA and their correlation with clonal plasma cells' phenotype in patients with ND MM. Methods. We analysed 22 patients with ND MM (median age 57 years, range 38-80; male/female - 1:1.75). Cytogenetic analysis was performed on bone marrow samples using standard GTG-method. Metaphase FISH analysis was performed according to the manufacturer's protocol using DNA probes: LSI 13(RB1)13q14, IGH/CCND1, IGH/FGFR3, LSI TP53 (17q13.1). 8-color immunophenotypic by flow cytometry using antibody to CD45, CD38, CD138, CD56, CD19, CD20, CD27 and CD117 antigenes. Results. Translocation t(11;14) was detected in 3/14 (21.4%) patients, del(13q) - 2/14 (14.3%), t(11;14) - 3/14 (21.4%), hypodyploidy - 1/20 (5%), del(17р) - 0% patients. Clonal plasma cells' phenotype CD38+CD138+CD45- was detected in 100%. Expression CD56+ was revealed in 11/22 (50%) patients, CD19+ in 9/22 (40.9%), CD117+ in 5/22 (22.7%), CD20+ in 1/22 (4.5%), CD27+ in 1/22 (4.5%). The frequency of GA didn't depend on clonal plasma cells' phenotype and was 27.3%(3/11) in CD56+ phenotype, 23.8%(5/21) - CD20-, 23.8%(5/21) - CD27-, 23.5%(4/17) - CD117-, 23%(3/13) - CD19-, 22.2%(2/9) - CD19+, 20%(1/5) - CD117+, 18.2%(2/11) - CD56-, 0%(0/1) - CD20+, 0%(0/1) - in CD27+ phenotype. Patients of standard risk group according to mSMART 2.0 with GA had CD19-negative plasma cells' phenotype vs. CD19-positive phenotype in patients of intermediate and high-risk groups (p<0.05). 3-years overall survival in standard risk group with CD19- phenotype was 92,3%, CD19+ - 77,7% (p>0.05). Conclusion . Identification of GA, which has adverse forecast, correlates with CD19+ plasma cells phenotype. The combined definition of plasma cells phenotype and GA can improve the system of risk stratification in MM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Significance of Modified Risk Stratification Msmart 3.0 and Autologous Stem Cell Transplantation for Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5593-5593
Author(s):  
Andrey Garifullin ◽  
Sergei Voloshin ◽  
Vasily Shuvaev ◽  
Irina Martynkevich ◽  
Elizaveta Kleina ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Group ◽  
High Risk Group ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Genetic Abnormalities ◽  
Standard Risk

Background The risk-stratification systems are repeatedly updated in accordance with the emergence of new information about the prognostic impact of anomalies and other factors. The most extensive and modern system in this time is mSMART risk stratification involving many parameters such as genetic anomalies, albumin, beta-2-microglobulin, LDH, Plasma Cell S-phase and GEP levels. It is possible to use risk-adapted treatment programs with or without ASCT. Nevertheless, the role of complex karyotype, combination of genetic abnormalities and ASCT remains unclear. Aims To estimate the genetic abnormalities in patients with newly diagnosed multiple myeloma and define the role of risk-stratification and ASCT in prognosis of disease. Methods The study included 159 patients (median age 63 years, range 28 - 83; male: female ratio - 1:1.37) with NDMM. Metaphase cytogenetics on bone marrow samples was done by standard GTG-method. FISH analyses were performed according to the manufacturer's protocol for detection primary IgH translocations, 13q (13q14/13q34) deletion, 1p32/1q21 amplification/deletion, P53/cen 17 deletion (MetaSystems DNA probes). We additional searched the t(4;14), t(6;14), t(11;14), t(14;16) and t(14;20) in patients with IgH translocation. All patient was treated by bortezomib-based programs (VD, CVD, VMP, PAD). ASCT was performed at 42% patients. Results The frequency of genetic abnormalities in NDMM patients was 49% (78/159). IgH translocation was detected in 26.4% (42/159) patients: t(11;14) - 16.3% (26/159), t(4;14) - 5.0% (8/159); TP53/del17p - 5.6% (9/159); 1p32/1q21 amp/del - 12% (19/159); hypodiploidy - 3.1% (5/159); hyperdiploidy - 1.25% (2/159); del5q - 0,6% (1/159); other - not found. Combination two aberrations was discovered in 11.9% (19/159) patients, complex abnormalities (>3 aberrations) - in 4.4% (7/159) patients. The median OS in "two aberration" and "complex abnormalities" groups were lower than in standard-risk mSMART 3.0 (normal, t(11;14), hypodiploidy, hyperdiploidy and other): 49 months, 26 months and was not reached, respectively (p=.00015). The median PFS for these groups was 12 months, 11 months and 30 months, respectively (p=.011). Differences between "two aberration" and "complex abnormalities" groups were not find (p> .05). We modified high-risk (gain 1q, p53 mutation, del 17p deletion, t(4;14), t(14;16), t(14;20), R-ISS stage III, double and triple hit myeloma) mSMART 3.0 by adding "two aberration" and "complex abnormalities" groups on based the OS and PFS results. The final analysis was based on the results of the complex examination of 87 patients: 53 patients in standard-risk group and 34 patients in high-risk group. The median OS in standard-risk mSMART 3.0 was not reached, in high-risk mSMART 3.0mod - 48 months; 5-years OS was 62% and 38%, respectively (p=0.0073). The median PFS was 43 and 29 months, respectively (p=.09). The best results of OS and PFS were reach in both groups of patient who performed ASCT. The median OS in standard-risk mSMART 3.0 with ASCT (n=37) was not reached, in high-risk mSMART 3.0mod with ASCT - 48 months (n=20); standard-risk mSMART 3.0 without ASCT - 40 months (n=16); in high-risk mSMART 3.0mod without ASCT - 22 months (n=14); 5-years OS was 81%, 60%, 33% and 28%, respectively (p=0.0015). The median PFS was not reached, 46, 22 and 19 months, respectively (p=.017). Conclusions The combination of two aberrations and complex abnormalities is unfavorable prognostic markers. The median OS and PFS was higher in standard-risk than high-risk group according mSMART 3.0mod. The ASCT can improve treatment's outcomes and life expectancy especially in patients with high-risk. It can be useful for update risk stratification in a future. Disclosures Shuvaev: Novartis: Consultancy; Pfize: Honoraria; Fusion Pharma: Consultancy; BMS: Consultancy.

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