P-128: Accompanying with additional complex karyotype is a poor prognostic factor in patients with multiple myeloma with high-risk cytogenetics in the era of novel agents

2021 ◽  
Vol 21 ◽  
pp. S105
Author(s):  
Hideki Uryu ◽  
Noriko Nishimura ◽  
Yuko Mishima ◽  
Yuko Ishihara ◽  
Yuko Shirouchi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Prognostic Factor ◽  
Novel Agents ◽  
Complex Karyotype ◽  
Poor Prognostic Factor

scholarly journals Prognostic Impact of Hyperdiploidy on Multiple Myeloma in the Era of New Agents

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-20
Author(s):  
Yi Wang ◽  
Jing Zhuang ◽  
Gang An ◽  
Xue-Han Mao ◽  
Chenxing Du ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Prognostic Factor ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Univariate Analysis ◽  
Medical Science ◽  
Novel Agents ◽  
Prognostic Impact ◽  
Complex Karyotype

Introduction Multiple myeloma (MM) is a kind of hematological malignancy which is characterized by high genetic heterogeneity. It has been proved that the existence and even the coexistence of numerical and structural cytogenetic abnormalities (CAs) play a critical role in the development and progression of MM. Hyperdiploidy (HD), as one of the two primary CAs of MM, can be observed in around half of the patients and is considered as a favorable prognostic factor. Nevertheless, its role in overcoming the negative effect of concomitant high-risk CAs remains controversial. Although the outbreak of novel drugs by the last decades, such as proteasome inhibitors (PIs) and Immunomodulatory drugs (IMiDs), has significantly improved the survival of patients, MM is still incurable and can relapse recurrently. The prognostic impact of HD in the era of novel agents and its impact on other CAs are unclear and under to be explored. Here, we report our results based on the Chinese population to provide some evidence for the above questions. Methods A total of 213 patients between January 2013 to November 2017 were included in this study. All of the participants were from our database consisting of patients with newly diagnosed MM (NDMM) enrolled into the prospective, nonrandomized clinical trial (BDH 2008/02 or BDH 2014/03, all informed consents were obtained) approved by Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College. According to patients' willingness and specific conditions, they were assigned to either PI- or IMiD-based inductive treatment and maintenance, with or without autologous stem cell transplantation (ASCT) as consolidation therapy. Bone marrow aspirate samples were collected before the initiation of therapy and MM cells were enriched by CD138 magnetic beads. Then fluorescence in situ hybridization (FISH) was performed. Specifically, if patients possessed at least an extra copy of probes for any two of chromosomes 5, 9, or 15 concurrently in more than 10% cells, they would be classified into HD subgroup; otherwise, they would be divided into NHD (non-hyperdiploidy) subgroup. Clinical and biological baseline characteristics were compared. Progression-free survival (PFS) and overall survival (OS) were measured using the log-rank test. Significant variables from the univariate analysis were selected for the cox stepwise regression analysis. Results In our cohort, HD was identified in 34% (72/213) NDMM patients. HD was more common among older people (p=0.007). Patients with HD often had a lower level of serum albumin (p=0.037), but NHD patients had a higher frequency of elevated lactate dehydrogenase (LDH). Moreover, immunoglobulin isotype distribution was not similarly (p<0.001), in which patients with NHD were more often IgD or light chain isotype. As to the genetics aspect, 99.1% (211/213) patients harbored at least one CA, and NHD patients appeared to be more genetic instability. 14q32 (IGH) translocation(p<0.001), del(13q) (p<0.001) and del(17p) (p=0.012) were likely to be detected in patients with NHD. However, there were no significant differences in the ratio of 1q21 gain/amplification and complex karyotype. Among patients with IGH translocation, t(14;undefined) [could not find partner genes by t(4;14), t(11;14), t(14;16) or t(14;20) probes] and t(11;14) were the most common translocation type in HD and NHD patients respectively. Median follow-up was 37 (4-82) months, Patients with HD showed a better median PFS (41 months vs. 27 months, p=0.047) and median OS (75 months vs. 55 months, p=0.024). Further subgroup analysis showed that the prolonged survival of HD was significant in patients who did not receive ASCT as part of the first-line therapy, but it could not overcome negative prognostic effects of other CAs except complex karyotype. Multivariate analysis confirmed that the state of ploidy was an independent prognostic factor for MM. Conclusions HD patients have specific differences in clinical and biological features. In the era of novel agents, MM patients with HD still have better survival than NHD. However, it may not ameliorate the adverse prognosis of concurrent high-risk CAs identified by FISH. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Development and Analysis of a Weighed Prognostic Model in Newly Diagnosed Multiple Myeloma Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-48
Author(s):  
Xue-Han Mao ◽  
Yan Xu ◽  
Yuting Yan ◽  
Jiahui Liu ◽  
Huishou Fan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Prognostic Factor ◽  
Prognostic Model ◽  
Cytogenetic Abnormalities ◽  
Total Score Range ◽  
Prognosis Model

Background and Objective: Multiple myeloma (MM) is characterized with significant cytogenetic changes and complex tumor microenvironment, thus patient survival is extremely heterogeneous. Various disease-related or patient-related factors affect the prognosis of patients. This study tried to analyze the prognostic indicators of patients with newly-treated MM, especially explored the prognosis of multiple cytogenetic abnormalities and the ratio of lymphocytes to monocytes (LMR). Additionally, we established a comprehensive prognostic model to help determine the patient prognosis. Methods: After screening, 603 patients of untreated MM from January 2008 to June 2017, with complete baseline indicators were enrolled into the study. By univariate and multivariate Cox analysis, risk factors related to the prognosis of patients were evaluated, and a weighted prognosis model was established to compare the survival differences of patients in each risk stratification. Result: Optimal thresholds of ALC, LWR, NLR and LMR were determined by ROC curve and Youdex index: ALC = 1.415, LWR = 0.325, NLR = 1.935, LMR = 2.95. Survival analysis showed that patients with LMR ≤ 2.95, ALC ≥ 1.415 and LWR ≥ 0.325 had significantly better survival compared with their respective control groups. Cox multivariate analysis showed that among the four indicators, only LMR≤2.95 was an independent adverse prognostic factor for overall survival (OS)(Figure 1A). 17p deletion, 1q21 amplification, t (4; 14) / t (14; 16) were define as high-risk cytogenetic abnormalities (HRA). Of the 603 patients, about 60% were associated with at least one high-risk cytogenetic event. Among them, the occurrence of cumulative 0, 1, 2, and 3 HRA were 39.6% (239/603), 42.5% (256/603), 16.6% (100/603), and 1.3% (8/603), respectively. There was no significant difference in survival among patients with same number of HRAs. The median OS of patients with 0, 1 and ≥ 2 HRA were not reached, 62.1 months (95% CI, 49.3-74.9) and 30.4 months (95% CI, 24.5-36.3), respectively (p <0.001)(Figure 1B).Final Cox regression model showed that age 65 ~ 74 (HR=1.77, 95%CI, 1.24-2.51, p=0.001), age ≥75 (HR=2.46, 95%CI, 1.69-3.58, p < 0.001), LDH≥247 U/L (HR =1.65, 95%CI, 1.07-2.51, p=0.023), ISS stage III (HR=1.76, 95%CI, 1.24-2.50, p=0.002), LMR≤2.95 (HR=1.53, 95%CI, 1.08-2.18, p=0.017), 1 HRA (HR=1.87, 95%CI, 1.27-2.75, p=0.002) and ≥2 HRA (HR=3.48, 95%CI, 2.22-5.45, p<0.001) are independent adverse prognostic factors for OS. Then weighted risk factors were summed to establish a comprehensive prognosis model, with a total score range of 0-6 points. Accordingly, the whole cohort was divided into low risk (0-1 points, 45.4%), intermediate risk (2 points, 27.9%), high risk (3 points, 19.2%) and ultra-high risk (4-6 points, 7.5 %) groups. The median OS of the four risk groups were 85.8 months (67.1-104.5), 49.0 months (44.7-53.3), 35.4 months (31.3-39.5), and 23.2 months (18.8-27.6), respectively (p<0.001). The C-statistics of this prognostic model is 0.68 (95% CI, 0.64-0.71), which is significantly better than the D-S stage (C-statistics = 0.52, 95% CI, 0.50-0.55, p <0.001), ISS (C-statistics = 0.60, 95% CI, 0.57-0.64, p <0.001) and R-ISS stage (C-statistics = 0.60, 95% CI, 0.57-0.63, p <0.001). Bootstrap resampling and calibration curve showed that the model has an accurate predictive effect on both short-term and long-term prognosis of patients(Figure 1C). Conclusion: In our analysis, ALC, LWR, LMR were associated with poor prognosis in NDMM patients, while NLR had no significant prognostic significance. Among the four indicators, LMR≤2.95 was the only independent prognostic factor. In NDMM patients, survival of patients with the same number of high-risk cytogenetic abnormalities were comparable with each other, regardless of whichever combination of HRA. Higher number of high-risk cytogenetic abnormalities were associated with worse prognosis. Cox multivariate analysis showed that, old age (65-74 years old, ≥75 years old), increased LDH (≥247 U/L), decreased LMR (≤2.95), ISS III, 1 HRA and ≥ 2 HRA were independent adverse prognostic factors that affect the OS of MM patients. 4. A comprehensive weighted prognostic model was established with the above factors, which was proved to effectively distinguish different prognosis of patients. Figure 1 Disclosures No relevant conflicts of interest to declare.

scholarly journals Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Zhiwen Xiao ◽  
Guopei Luo ◽  
Chen Liu ◽  
Chuntao Wu ◽  
Liang Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Event ◽  
High Risk ◽  
Prognostic Factor ◽  
Lymphatic Metastasis ◽  
Clinical Course ◽  
Cellular Mechanisms ◽  
Poor Prognostic Factor ◽  
Dismal Prognosis ◽  
Low Rate

As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs) and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

Expression of Interferon Regulatory Factor-4 (IRF4/MUM1) Is Associated with Inferior Overall Survival In Peripheral T-Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 140-140
Author(s):  
Andrew L Feldman ◽  
Ahmet Dogan ◽  
Matthew J Maurer ◽  
Thomas M Habermann ◽  
Patrick B Johnston ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
T Cell ◽  
Prognostic Factor ◽  
Interferon Regulatory Factor ◽  
Minor Allele ◽  
Regulatory Factor ◽  
Poor Prognostic Factor ◽  
T Cell Lymphomas ◽  
Interferon Regulatory Factor 4

Abstract Abstract 140 Background: Peripheral T-cell lymphomas (PTCLs) have poor outcomes, and there is a lack of prognostic biomarkers and therapeutic targets to guide treatment. We recently proposed that the transcription factor, interferon regulatory factor-4 (IRF4, also called multiple myeloma oncogene-1 [MUM1]), might be oncogenic in PTCLs based on its expression in association with translocations between IRF4 and the T-cell receptor gene, TRA@. IRF4 is a therapeutic target in multiple myeloma, where high expression is a poor prognostic factor. In addition, at least two germline IRF4 single nucleotide polymorphisms (SNPs), rs12203592 and rs872071, are associated with IRF4 expression and disease risk and progression in various lymphoid neoplasms. However, the prognostic effects of IRF4/MUM1 expression and IRF4 SNPs in PTCLs are unknown. Methods: Forty seven newly diagnosed PTCL patients with available tissue were identified from the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource. There were 5 anaplastic large cell lymphomas, 14 cutaneous T-cell lymphomas (CTCLs), 6 cytotoxic T-cell lymphomas (cytTCLs: 4 extranodal NK/T-cell and 2 enteropathy type), and 22 PTCLs, not otherwise specified (NOS). Patients were diagnosed between September 2002 and February 2008 and systematically followed through March 2010 for overall survival (OS). Tumor cell IRF4/MUM1 expression was examined by immunohistochemistry on paraffin tissue sections (MUM1p clone; Dako). Positivity was defined as >30% of tumor cells with nuclear staining, as in previous studies. rs12203592 and rs872071 were genotyped in peripheral blood DNA. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for both IRF4/MUM1 expression and SNPs with OS. Chi-squared tests were used to assess the relationship between IRF4/MUM1 expression and IRF4 SNPs. Results: The median age at diagnosis was 60 years (range, 24–88). At a median follow-up of 62 months (range, 29–89), 22 (47%) of the patients had died. Fifteen (32%) of the 47 T-cell patients had IRF4/MUM1 positive tumors. IRF4/MUM1 positivity was associated with poorer overall survival (HR=4.3; 95% CI: 1.8–10.2; p=0.0008). This association was seen across PTCL subtypes, including PTCL, NOS (HR= 6.5; 95% CI: 1.5–27.7; p=0.01), CTCL (HR=13.4; 95% CI: 1.2–150.1; p=0.03), and cytTCL (HR=5.8; CI: 0.5–65.9; p=0.15). The minor allele (T) in SNP rs12203592 was positively associated with IRF4/MUM1 positivity in a dominant model, with IRF4/MUM1 expression in 60% of patients with CT or TT genotypes compared to 19% of patients with CC genotype (p=0.01). Patients with the CT/TT genotype at rs12203592 also had inferior overall survival (HR=3.7; 95% CI: 1.4–9.5; p=0.007). The rs872071 SNP showed no significant association with either IRF4/MUM1 expression (p=0.38) or overall survival (p=0.71). Conclusions: This study is the first to demonstrate that IRF4/MUM1 expression is poor prognostic factor in PTCLs. This association was observed across PTCL subtypes, including the most common subtype, PTCL, NOS. IRF4/MUM1 expression and poor survival in our patients also were associated with the minor allele (T) in the IRF4 SNP rs12203592; these findings are consistent with previous in vitro data showing the major allele (C) represses IRF4 promoter activity. Interestingly, rs872071 was not associated with IRF4/MUM1 expression or prognosis, similar to findings in multiple myeloma. In contrast, rs872071 is a risk and prognostic factor in chronic lymphocytic leukemia and classical Hodgkin lymphoma, diseases in which IRF4/MUM1 expression has been associated with favorable prognosis. IRF4/MUM1 expression is a poor prognostic factor in PTCLs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Revised International Staging System (R-ISS) for Transplant-Eligible Multiple Myeloma Patients Risk Stratification

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5756-5756
Author(s):  
Telma Nascimento ◽  
Adriana Roque ◽  
Emília Cortesão ◽  
Luís Francisco Araújo ◽  
Ana Isabel Espadana ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Partial Response ◽  
Risk Stratification ◽  
Real Life ◽  
Staging System ◽  
Stage Ii ◽  
Novel Agents ◽  
International Staging System

Abstract BACKGROUND: In the last decades, multiple myeloma (MM) prognosis has been changing dramatically. Induction with novel agents, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (aHSCT) is the standard of care for newly diagnosed (ND) and transplant-eligible MM patients (pts). In 2015, a new score was validated [Revised International Staging System (R-ISS)], including data related to high-risk cytogenetic abnormalities (CA) [del(17p) and/or t(4;14) and/or t(14;16)] and serum lactate dehydrogenase (LDH) levels. Few recent studies have supported R-ISS as a reliable prognostic tool for estimating survival in MM pts submitted to aHSCT. AIMS: To determine whether R-ISS is a valid risk model for predicting progression free survival (PFS) and overall survival (OS) among a cohort of real-life aHSCT pts. METHODS: We conducted a single center retrospective study of ND symptomatic MM pts treated with novel agents (bortezomib, thalidomide or lenalidomide) undergoing aHSCT between Jan/2007 and Dec/2017. We excluded all pts with no available information about ISS, LDH and CA [detected by fluorescence in situ hybridization (FISH)]. Response to treatment was evaluated according to the International Myeloma Working Group consensus criteria (2016). Statistical analysis was performed using STATA v.14.2 and significant levels were set at p<0.05. RESULTS: From the total number of 186 pts submitted to aHSCT, only 81 (45%) pts presented criteria to be included in our analysis; 62% were male, with a median age at aHSCT of 60y (28-70). IgG was the most frequent subtype (59%), followed by IgA (20%). At diagnosis, 38% of pts presented anemia, 14% renal impairment (RI), 20% hypercalcemia, 63% bone disease (BD) and 32% extramedullary disease (EMD). According to ISS, 30 (37%) pts presented stage I, 30 (37%) stage II, and 21 (26%) stage III at diagnosis. There were 38% pts with high-risk CA: 24% with del17p; 19% with t(4;14), and 20% with t(14;16). High LDH levels was seen in 48% of pts. Pts were re-staged at diagnosis according to R-ISS, resulting 17% in stage I, 61% in stage II, and 22% in stage III. Thus, 16 (20%) pts previously categorized as ISS I and 3 (4%) pts as ISS III were re-classified as R-ISS II. Median time from diagnosis to aHSCT was 9.7 months. All pts received induction therapy with novel agents (a bortezomib-based therapy in 89% of pts and an IMID-based in 12%), with 81% of pts responding to first line induction; 19% were refractory. At the time of aHSCT, all pts presented at least on partial response (PR) [62% at least very good partial response (VGPR)], with an increase in the proportion of pts in complete response (CR) from 15% to 20% before and after aHSCT, respectively. Maintenance therapy was performed in 31% of pts (79% thalidomide; 21% lenalidomide). At a median follow-up of 33.4 months, median OS had not been reached. Two-years OS was 62%. Median PFS from aHSCT was 67.4%.Neither high-risk CA nor high LDH levels individually predicted lower OS and PFS (p=NS). The 2-year OS for R-ISS I, II and III was 86 %, 61% and 44%, and the 2-year PFS was 79 %, 63% and 39%, respectively. In our cohort we observed statistical significance differences between R-ISS I and III at 2 years in what concerns PFS (p=0.025) and OS (p=0.017) . No differences were seen in between other R-ISS categories. When we stratified R-ISS stage II in two subgroups based on the presence or absence of high-risk CA no differences were found. Pts classified as R-ISS III presented anemia (p<0.001) and RI (p=0.001) more frequently, but no differences concerning hypercalcemia, BD or EMD. CONCLUSIONS: In our real-life cohort, R-ISS at diagnosis was a reliable tool only to predict both OS and PFS between R-ISS I and III and not between other R-ISS subgroups. The main reasons that explain the absence of significance between all R-ISS subgroups were probably the very low number of pts with available cytogenetics compared with the total number of pts submitted to aHSCT in our center and the short follow up of our study. Larger real-life studies with a longer follow up are necessary to determine if R-ISS is a good risk stratification model to applicate to NDMM pts submitted to aHSCT in the era of novel agents. Disclosures No relevant conflicts of interest to declare.

scholarly journals Elevated Red Blood Cell Distribution Width as a Simple Prognostic Factor in Patients with Symptomatic Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Hyewon Lee ◽  
Sun-Young Kong ◽  
Ji Yeon Sohn ◽  
Hyoeun Shim ◽  
Hye Sun Youn ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factor ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Plasma Cells ◽  
Cell Distribution ◽  
Distribution Width ◽  
Poor Prognostic Factor ◽  
Inflammatory Biomarker ◽  
Red Blood Cell Distribution

Red blood cell distribution width (RDW) is a parameter reported in complete blood cell count tests, and has been reported as an inflammatory biomarker. Multiple myeloma (MM) is known to be associated with inflammatory microenvironments. However, the importance of RDW has been seldom studied in MM. For this study, 146 symptomatic myeloma patients with available RDW at diagnosis were retrospectively reviewed, and their characteristics were compared between two groups, those with high (>14.5%) and normal (≤14.5%) RDW. RDW was correlated to hemoglobin, MM stage,β2-microglobulin, M-protein, bone marrow plasma cells, and cellularity (P<0.001). During induction, overall response rates of the two groups were similar (P=0.195); however, complete response rate was higher in the normal-RDW group than it was in the high-RDW group (P=0.005). With a median follow-up of 47 months, the normal-RDW group showed better progression-free survival (PFS) (24.2 versus 17.0 months,P=0.029) compared to the high-RDW group. Overall survival was not different according to the RDW level (P=0.236). In multivariate analysis, elevated RDW at diagnosis was a poor prognostic factor for PFS (HR 3.21, 95% CI 1.24–8.32) after adjustment with other myeloma-related prognostic factors. RDW would be a simple and immediately available biomarker of symptomatic MM, reflecting the systemic inflammation.

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

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

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

IgD Myeloma: Clinical Features and Outcome In The Era Of Novel Agents

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1935-1935 ◽  
Author(s):  
Flora Zagouri ◽  
Efstathios Kastritis ◽  
Argiris S. Symeonidis ◽  
Nikolaos Giannakoulas ◽  
Eirini Katodritou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Renal Dysfunction ◽  
Light Chain ◽  
The Other ◽  
Novel Agents ◽  
Primary Therapy ◽  
Lambda Light Chain ◽  
Prognostic Features ◽  
High Risk Disease

Abstract IgD multiple myeloma is a rare variant of the disease and in various series accounts for about 2% of patients with symptomatic myeloma. It has been suggested that patients with IgD myeloma may have an inferior outcome when compared to other patients. However, data on IgD myeloma patients treated in the novel agent era are lacking. In order to assess the frequency and evaluate the outcome and the specific characteristics of patients with IgD myeloma we analyzed the database of the Greek Myeloma Study Group to identify such patients. Between January 2000 and December 2012, among the 1239 patients with previously untreated, symptomatic, myeloma, 31 patients (2.5%) were diagnosed with IgD myeloma. Of interest, 84% of patients with IgD myeloma had lambda light chain (versus 38% of the patients with other subtypes of MM, p<0.001). The median age of patients with IgD myeloma was 65 years (range 26-80 years) versus 68 years (range 23-96 years) for patients with other subtypes of MM (p=0.073), while 10% of patients with IgD versus 28% of the other patients were >65 years (p=0.023) and 10% of patients with IgD versus 3.8% of the other patients were ≤40 years of age. Patients with IgD myeloma presented more often with significant renal dysfunction (serum creatinine ≥2 mg/dl in 52% versus in 19%, p<0.001 or eGFR <30 ml/min/1.73m2 in 42% versus 18% in patients of other subtypes, p=0.001) and excreted larger amounts of Bence Jones protein (59% excreted ≥2 gr per day versus 17% of the other patients, p<0.001). Patients with IgD myeloma had also more often features of high risk disease including ISS-3 disease (60% versus 37% for the other patients, p=0.011) and elevated serum LDH (≥300 IU/L) in 29% versus10% of the other patients (p=0.001). Response to primary therapy for patients with IgD myeloma was similar to other patients (at least PR in 77% versus 72% respectively), although there was a trend for better quality of responses in patients with IgD myeloma (sCR and CR in 26% versus 15% of patients, and at least VGPR in 53% versus 29% in patients of other subtypes, respectively, p=0.059). However, more patients with IgD myeloma had received primary therapy with bortezomib-based regimens (40% versus 22%) and less often IMiD-based therapy (20% versus 35%), while similar proportions of patients received conventional chemotherapy-based regimens (40% versus 44%; p=0.043). Despite the increased frequency of features of high risk disease in patients with IgD myeloma, the median survival of these patients was 51.5 months versus 50.7 months for patients of other subtypes (p=0.850). In a multivariate model to adjust for differences in prognostic features, IgD myeloma was not associated with a different prognosis. We also compared the outcome of patients with IgD myeloma treated before and after January 1st, 2000. The survival of the patients with IgD myeloma who started therapy before versus after 2000 was 44 months (p=0.018). In conclusion, in a large series of patients with symptomatic multiple myeloma, the incidence of IgD myeloma is 2.5%. The vast majority of patients with IgD myeloma is associated with lambda light chain and present more often with significant Bence Jones proteinuria, significant renal dysfunction and features of advanced disease. However, their outcome in the era of novel agents is similar to that of patients with other myeloma subtypes. Disclosures: No relevant conflicts of interest to declare.

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