The Expression Of CD200 As a Prognostic Factor In Newly Diagnosed Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3082-3082
Author(s):  
Yi Li ◽  
Wenjun Wu ◽  
Jingsong He ◽  
Xiaoyan Han ◽  
Gaofeng Zheng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Staging System ◽  
Newly Diagnosed ◽  
New Approach ◽  
Myeloma Cells ◽  
Targeting Therapy ◽  
Molecular Therapeutic

Abstract Introduction multiple myeloma (MM) is currently an incurable hematological malignancy. Discovering molecular therapeutic targets is a new approach to improve the outcome in the treatment of the malignant disease. As CD200 is a type Ⅰmembrane glycoprotein expressed on myeloma cells, we asked if the expression of CD200 could serve as a prognostic marker for MM patients. Our data indicated that the expression level of CD200 is indeed correlated with the prognosis of the MM patients. Methods bone marrow samples from 96 newly diagnosed MM patients from April 2011 to July 2013 were evaluated by flow cytometry, using PE-conjugated anti-CD200 mAb, FITC-conjugated anti-CD138 mAb, and PE-Cy7-conjugated anti-CD45 mAb. PE-or FITC-conjugated normal mouse IgG was used as isotype-matched controls. Results 96 MM patients were investigated in the present study, including 60 men and 36 women, with a median age of 63 years (range 34–86 years). 81/96(84%) MM patients were CD200 positive with a median Mean Fluorescence Intensity (MFI) of 127 as analyzed by flow cytometry, which was consistent with the previous studies. While in 15 of 96 patients, CD200 expression was undetectable. Among the CD200 positive ones 7.40% patients were classified as stage Ⅰ, 12.35% were stage Ⅱ, and 80.25% were stage Ⅲ according to Durie–Salmon staging criteria. 40.74% patients were stageⅠ, 22.22% were stage Ⅱ, and 37.04% were stage Ⅲ, according to the International Staging System (ISS). Analysis of the CD200 positive patients revealed the MFI<127 group had a better progression free survival (PFS) (p=0.046) (Fig 1A) and overall survival (OS) (p=0.069) compared to those with MFI≥127. In the patients with age ≥65 years old, PFS (p=0.023) (Fig 1B) and OS (p=0.044) (Fig 1C) were much shorter in the MFI≥127 group, compared to the MFI<127 ones. Conclusions Our study demonstrated that the expression and MFI of CD200 on primary multiple myeloma cells is correlated with the prognosis of the MM patients. The better PFS and OS were observed in the MFI<127 group compared to the patients with MFI≥127, especially in the patients with age≥65 years old. Improved PFS in CD200 positive ones is likely due to the immune suppression mediated by CD200. Our study suggests that targeting therapy against CD200 may become a new approach to the treatment of MM in clinical practice. Disclosures: No relevant conflicts of interest to declare.

Bortezomib-Based Chemotherapy Regimens Can Inmprove The Complete Remission In Newly Diagnosed Multiple Myeloma Patients With Bcl-2 and Survivin Overexpression

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5349-5349
Author(s):  
Zeng Wen ◽  
Huang Lifang ◽  
Yicheng Zhang ◽  
Sun Hanying ◽  
Liu Wenli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Staging System ◽  
Chemotherapeutic Agents ◽  
Tumor Burden ◽  
Newly Diagnosed ◽  
Double Positive ◽  
Research Fields

Abstract Compared with the traditional chemotherapeutic agents, Bortezomib-based chemotherapy regimens can increase the complete remission and improve the prognosis significantly in the newly diagnosed multiple myeloma patients. Molecular markers which can predict the chemotherapeutic efficacy and safety could help the physicians to make the right decisions and benefit the patients, and it has been one of most interesting research fields in MM. It has been reported that Survivin and Bcl-2 was involved in the adverse clinical events and therapeutic resistance, respectively. In order to investigate the relationship between the Survivin and Bcl-2 expression and the different regimens therapeutic efficacy, we retrospectively studied the proteins expression in the bone marrow biopsy specimens by inmmunohistochemistry and the efficacy of different chemotherapy regimens in the newly diagnosed MM in a single center of Tongji Hospital. Total 59 newly diagnosed MM were admitted into this study. The positive expression rate for Survivin and Bcl-2 was 35.3%（n=21）and 73.5%（n=43）, respectively. The protein expression had no relationship with the Durie-Salmon and International Staging System stratification, which suggested that Survivin and Bcl-2 were not responsible for the clinical manifestations. Bortezomib-based regimens (n=22) could effectively decrease the tumor burden and achieve response (CR+PR: 67.5% ). The non-bortezomib regimens (n=37), containing VAD(T), MP(T), TAD, were effective in the absent of Survivn and Bcl-2 expression(n=7; CR+PR 62.5% ). When Survivin and Bcl-2 were single or double positive (n=30), the newly diagnosed MM patients had no response for non-bortezomib regimens with none reaching complete remission or partial remission (p=0.0088). According to this study, we recommend the newly diagnosed MM which were Survivin and Bcl-2 single or double positive by inmmunohistochemistry received the regimens containing bortezomib for anti-myeloma therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunophenotype Drift of Residual Plasma Cells Indicates Therapeutic Response and Prognosis in Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5491-5491
Author(s):  
Chenxing Du ◽  
An Gang ◽  
Yan Xu ◽  
Xuehan Mao ◽  
Yuting Yan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Therapeutic Response ◽  
Conflicts Of Interest ◽  
Early Stage ◽  
Therapy Group ◽  
Newly Diagnosed ◽  
Normal Phenotype ◽  
Group A ◽  
Group B

Background Chemotherapy resistance remains a significant hurdle in the treatment of multiple myeloma (MM). However, it is difficult to discriminate the potential refractory patients from the very early stage. Flow cytometry is a convenient tool to detect the residual myeloma cell tiding, indicating therapeutic response sensitively. Methods From June, 2014 to December, 2016, 172 sequential patients with newly diagnosed multiple myeloma were enrolled in the BDH2008/02 clinical trial. Patient informed consent was obtained in accordance with the Declaration of Helsinki. 144 patients with at least two flow cytometry detections were analyzed. Bone marrow samples were detected by an eight-color EuroFlow panel. CD20 negative and CD81 positive is defined as normal phenotype. Results We conducted a median of 3-time (2-8) flow cytometry detection on each patient. When newly diagnosed and achieved best response, CD20, CD81 expression rates were 29.9%, 9.7% and 14.9%, 64.4% (P=0.0091, P<0.0001), respectively. According to the status variation of CD20 and CD81, all patients were divided into three groups: both markers were always normal (Group A), either CD20 or CD81 was abnormal at diagnosed and turned normal during therapy (Group B) and markers stayed abnormal (Group C). Patients with undetectable residual tumor cells were also classified as Group A. The overall response rate of the patients in Group C was inferior to Group B (>PR rate: 54.3% vs. 71.4%, P=0.021). And the OS of Group C was significantly worse than Group A and B (47.9 months vs. not reached vs. not reached, P=0.036). Conclusion CD20/CD81 switching to normal phenotype during therapy indicates therapeutic response and an improved outcome than that staying abnormal. The expression tiding of CD20 and CD81 may be a reasonable combination to dynamically stratify MM patients, directing the choice of maintenance therapy. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Multiple Extramedullary-Bone Related and/or Extramedullary Extraosseous Are Independent Poor Prognostic Factors in Patients With Newly Diagnosed Multiple Myeloma

2021 ◽  
Vol 11 ◽  
Author(s):  
JingSong He ◽  
XiaoYan Yue ◽  
DongHua He ◽  
Yi Zhao ◽  
Yang Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Early Stage ◽  
Progression Free Survival ◽  
Staging System ◽  
Serum Lactate ◽  
Single Site ◽  
Serum Lactate Dehydrogenase ◽  
Newly Diagnosed ◽  
International Staging System

BackgroundExtramedullary (EM) lesions are common in multiple myeloma (MM) and are often related to the poor prognosis of MM but are scarcely understood.MethodsIn this retrospective study, the baseline characteristics of 357 newly diagnosed patients with extramedullary multiple myeloma (EMM) and their impact on the prognosis were analyzed. All patients received first-line treatment with bortezomib-based regimen.ResultsThe overall incidence rate of EM was 22.4%, and the detection rate of PET/CT was significantly higher than other imaging methods (P = 0.015). The cohorts consisted of 10 cases of extramedullary extraosseous (EME) and 70 cases of extramedullary-bone related (EMB), including 53 cases with single site involvement (one case with EME) and 27 cases with multiple sites (&gt;1 site) involvement (nine cases with EME). EMM patients had high levels of hemoglobin (Hgb, ≥10 g/dl) and serum lactate dehydrogenase (LDH, &gt;245u/L) and are inclined to early-stage revised international staging system (R-ISS). Compared to patients without EM, those with EMM had worse progression-free survival (PFS) (P = 0.014) and overall survival (OS) (P = 0.032). In addition, patients without EM and those with a single site of EMB had similar PFS and OS, while patients with multiple sites of EMB or EME and multiple sites of EMB with EME had poor PFS and OS. Multivariate analysis confirmed that multiple sites of EMB and/or EME were independent prognostic predictors affecting PFS and OS in newly diagnosed MM patients.ConclusionsThis study suggested that among patients treated with bortezomib-based regimens, multiple sites of EMB and/or EME are independent poor prognostic factors for newly diagnosed MM patients, while a single site of EMB does not affect the survival of newly diagnosed MM patients. Thus, these findings could be used as a reference for the study of EMM patients in the new drug era, but prospective clinical studies are needed to provide evidence-based data for the diagnosis and treatment of EMM.

MAGE-A Inhibits Apoptosis In Proliferating Multiple Myeloma Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 785-785
Author(s):  
Tricia Nardiello ◽  
Achim A Jungbluth ◽  
Anna Mei ◽  
Maurizio DiLiberto ◽  
Xiangao Huang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Independent Set ◽  
Cell Cycle Checkpoints ◽  
Type I ◽  
Newly Diagnosed ◽  
Ki 67 ◽  
Myeloma Cells ◽  
Apoptosis Protein ◽  
The Impact

Abstract Abstract 785 The type I Melanoma Antigen GEne (MAGE) MAGE-A3 is commonly present in primary multiple myeloma cells and its expression is correlated with advanced disease and proliferation. MAGE-A3 belongs to the Cancer-Testis antigen (CTAg) family of tumor-associated proteins, which are present in many cancers, but their normal expression is limited to developing germ cells and placental trophoblast. This unique expression pattern fuels speculation on a role for CTAg in oncogenesis; however, very little is known about their function. In gene expression analyses of primary myeloma cells, CTAg were associated with proliferative gene signatures and poor clinical outcome, suggesting they contribute to the pathogenesis or progression of this disease through effects on survival and/or proliferation of myeloma cells. To investigate this, we examined the impact of MAGE-A on disease progression, proliferation, and apoptosis in primary myeloma specimens and human myeloma cell lines (HMCL). MAGE-A3 protein expression was examined by immunohistochemistry in a new, independent set of myeloma bone marrow specimens from two critical clinical milestones, newly diagnosed, untreated patients and patients who relapsed after chemotherapy. MAGE-A3 was detected in a higher percentage of tumor specimens from relapsed patients (77%) compared to those from newly diagnosed patients (36%, p=0.0003). The percentage of proliferating myeloma cells, as measured by staining for the proliferation marker Ki-67, was significantly higher in relapsed specimens (19.0 ± 3.5%) compared to newly diagnosed (6.9 ± 1.3%, p=0.0002), demonstrating a correlation between MAGE-A3, progression of disease and proliferation. The mechanisms for MAGE-A3 activity were investigated by silencing this gene in primary myeloma cells and HMCL by shRNA interference. Targeted lentiviral shRNA transduction efficiently knocked down MAGE-A3 mRNA and protein in MM.1r (p53+/+) and ARP-1 (p53−/−) HMCL and in primary myeloma cells by 48 hours, and this effect was maintained up to 96 hours. Silencing of MAGE-A did not affect cell cycling, as this intervention did not affect the phosphorylation of the Retinoblastoma gene product (Rb) that is required for progression through the G1 cell cycle checkpoints and entry into S phase. In contrast, MAGE-A was required for survival of proliferating myeloma cells. Silencing of MAGE-A led to a precipitous loss of viable cells within 48–72 hrs compared to controls. This was due to activation of intrinsic apoptosis, as demonstrated by increased annexin V staining, loss of mitochondrial membrane polarization, and cleavage/activation of caspase-9. These effects of MAGE-A knock-down were completely reversed by the pan-caspase inhibitor Quinoline-Val-Asp-CH2-OPh. Apoptosis after MAGE-A silencing appeared to be mediated by at least two distinct mechanisms; p53-dependent activation of pro-apoptotic Bax and Bak expression and reduced expression of the Inhibitor of Apoptosis Protein survivin through both p53-dependent and independent mechanisms. These results demonstrate that MAGE-A plays a role in the survival of proliferating multiple myeloma cells through the regulation of two critical apoptotic mechanisms. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Expression of CRBN Signaling Pathway Proteins Assessed By Immunohistochemical Staining As Candidate Biomarkers for Outcome in Myeloma Patients Treated with IMiDs

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1909-1909
Author(s):  
Lijuan Chen ◽  
Qinglin Shi ◽  
Rong Wang ◽  
Xiupan Lu ◽  
Yan Gu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Signaling Pathway ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Expression Level ◽  
Positive Staining ◽  
Myeloma Cells ◽  
Low Level ◽  
First Line Therapy

Abstract Cereblon (CRBN), Ikaros (IKZF1), Aialos (IKZF3) and multiple myeloma oncogene 1 (MUM1) are important component of CRBN signaling pathway when treat MM cells with IMiDs. CRBN interacts with the DNA damage-binding protein-1 (DDB1), Cullin 4 (Cul4A or Cul4B) and regulator of Cullins 1 (ROC1) to form the functional E3 ubiquitin ligase complex (E3ULC). CRBN increases the interaction between E3ULC and IKZF1/3, leading to increased ubiquitination degradation of IKZF1/3, and then induce cytotoxicity in myeloma cells. Subsequently, degradation of IKZF1/3 induce depression of multiple myeloma oncogene 1 (MUM1), which is also called interferon regulatory factors (IRF4) and proved to be involved in the anti-MM activity of IMIDs in previous studies. Immunohistochemical (IHC) staining may be a convenient approach for researchers to differentiate the myeloma cells and non-myeloma cells in BM samples. In this study, we evaluated CRBN, IKZF1/3 and MUM1 expression level in bone marrow (BM) by immunohistochemical (IHC) staining and investigated the relationship between expression level and treatment outcome after IMiDs-based or bortezomib-based therapy in 123 newly diagnosed multiple myeloma (NDMM) patients. H-score method was applied according to both intensity and extent of staining. The intensity was graded from 0 to 3("0"for absent staining, "1" for weak expression, "2" for intermediate expression, and "3" for strong expression of the protein). The extent was graded from "0" to "100" to represent the percentage of MM cells with positive staining of any intensity. H-score was obtained by multiplying the intensity and extent score, ranging from 0 to 300, which reflected protein expression level in MM cells. The median H-score of CRBN, IKZF1, IKZF3 and MUM1 were 200, 0, 180 and 180, respectively. According to the median H-score, we classified the patients into high or low expression group. One hundred and twenty-three NDMM patients were enrolled in this study, including 64 males (52.0%) and 59 females (48.0%). The median age was 60 years (range 34-84). Fifty-one patients (41.5%) received IMiDs-containing regimen as the first-line therapy. The median follow-up time was 24.0 months (range, 10-76 months). After treated with IMiDs, patients with high level of CRBN and MUM1 achieved better overall response rate (ORR) than those expressed low level (CRBN, 88.0% vs. 42.3%, P=0.001; MUM1, 83.3% vs. 48.1%, P=0.009). Besides, patients with CRBN and MUM1 overexpression also had better overall survival (median OS, CRBN, not reached vs. 21.0 months, P=0.004; MUM1, not reached vs. not reached, P=0.021) and progression free survival (median PFS, CRBN, 28.0 vs. 12.0 months, P=0.002; MUM1, 32.0 vs. 12.0 months, P<0.001) than patients with low level, as well as 2-year OS rate (CRBN, 86% vs. 44%, P=0.005; MUM1, 81% vs. 51%, P=0.003) and PFS rate (CRBN, 66% vs. 17%, P=0.001; MUM1, 63% vs. 20%, P<0.001). In addition, in high CRBN and MUM1 expression group, patients treated with IMiDs had a higher 2-year PFS rate than Bortezomib presentation (CRBN, 66% vs. 45%, P=0.004; MUM1, 63% vs. 36%, P=0.003). In low CRBN and MUM1 expression group, patients treated with IMiDs had an inferior OS (median OS, CRBN, 21.0 vs. 57.0 months, P=0.001; MUM1, not reached vs. 57.0 months, P<0.001) and PFS (median PFS, CRBN, 12.0 vs. 31.0 months, P=0.003; MUM1, 12.0 vs. 32.0 months, P<0.001) than patients with Bortezomib, as well as 2-year OS rate (CRBN, 44% vs. 91%, P=0.002; MUM1, 51% vs. 100%, P<0.001) and PFS rate (CRBN, 17% vs. 59%, P=0.010; MUM1, 20% vs. 68%, P<0.001). This study identified high levels of CRBN pathway proteins CRBN and MUM1 were correlated with favorable ORR and survival in NDMM patients with IMiDs therapy, also suggested that expression levels of CRBN signaling pathway proteins in plasma cells assessed by IHC staining could better direct clinic individualized therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Outcomes of Non-Traditional Lenalidomide, Bortezomib, and Dexamethasone Regimens in Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Shawn O. Streeter ◽  
Omar Nadeem ◽  
Paul G. Richardson ◽  
Jacob P. Laubach ◽  
Clifton C. Mo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Descriptive Analysis ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Staging System ◽  
Newly Diagnosed ◽  
Cutaneous Toxicity ◽  
Free Survival ◽  
Significant Difference

Introduction Lenalidomide, bortezomib, and dexamethasone (RVD) is a standard first-line regimen for patients with newly diagnosed multiple myeloma and is associated with high response rates and improvement in progression-free survival and overall survival compared to traditional chemotherapy regimens. Traditional (RVD Classic, RVD Lite) and non-traditional (RVD Premium Lite, RVD Ultra Lite) variations of the RVD regimen are utilized at Dana-Farber Cancer Institute (DFCI) and have not been fully evaluated in terms of safety and tolerability. RVD Premium Lite is administered in a 28-day cycle with weekly bortezomib; whereas, RVD Ultra Lite administers three weekly doses of bortezomib instead of four (Table 1). These two regimens have not been fully evaluated in terms of safety, tolerability, and efficacy. Selection is based on provider preference in addition to flexibility of dosing schedule. The regimens also allow for convenience of weekly dosing while keeping dose intensity. This retrospective, descriptive analysis is the first study to explore the safety, tolerability, and efficacy of four different RVD regimens used at DFCI. Methods This single-center, retrospective, descriptive analysis identified 90 newly diagnosed patients with multiple myeloma treated at DFCI main campus for &gt;2 cycles of an RVD-based regimen in the front-line setting. We reviewed patients started on treatment from January 2017 to December 2019. Patients were excluded if treated primarily at an outside institution or satellite campus. Results A total of 90 patients were included between January 2017 to December 2019, and median age was 69.5 years (range 44-87). Most patients had either standard-risk or unknown cytogenetics. Of the 44 patients with available International Staging System (ISS) information, the majority were R-ISS/ISS I or II. The most common M-protein type at diagnosis was IgG (56.7%), followed by light chain restricted disease (25.6%). In terms of traditional and non-traditional RVD regimens, most patients received RVD Classic (33.3%) or RVD Ultra Lite (32.2%), followed by RVD Lite (23.3%) and RVD Premium Lite (11.1%). Patients in RVD Lite and RVD Ultra Lite groups were of older age when compared to the RVD Classic group (P&lt;0.001). Lenalidomide dosing delays and reductions trended higher in the RVD Classic regimen at 14.3%, followed by RVD Ultra Lite at 12.3%. Bortezomib dosing delays and reductions were similar between the RVD Lite and RVD Classic regimens at 11.8% and 11.2%, respectively. Overall, combined lenalidomide and bortezomib dosing delays/reductions trended higher in the RVD Classic (14.3%/11.2%) and RVD Lite (11.0%/11.8%) compared to RVD Ultra Lite (12.3%/9%) and RVD Premium Lite (10.8%/9.6%). The most common toxicities noted with all variations of the RVD regimen were peripheral neuropathy, cutaneous toxicity, infection, diarrhea, and constipation. The highest rates of adverse events among all RVD regimens were infection and peripheral neuropathy. Peripheral neuropathy was slightly higher in the RVD Premium Lite and RVD Classic regimen at 8.43% and 8.70%, respectively, compared to RVD Lite and RVD Ultra Lite at 7.1% and 7.7%, respectively. No significant difference in toxicities were seen when regimens were compared (p=0.1369). Intolerance leading to therapy change trended higher in the RVD Lite group at 23.8%, followed by RVD Classic and RVD Ultra Lite at 16.7% and 10.3%, respectively. Nineteen percent of patients in the RVD Lite group had minimal response or progression leading to therapy change, which was highest among all RVD regimens. Rate of transplant was highest in the RVD Classic group at 36.7%, followed by RVD Premium Lite at 20%. There was no significant difference in intolerance, minimal response or progression, maintenance, continued induction or planned change, transplant, and death between regimens (p=0.089). In terms of progression-free survival, no differences were seen between the groups (p=0.36). Conclusion In conclusion, the current investigation allowed us to assess the safety, tolerability, and efficacy of traditional and non-traditional variations of the RVD regimen in multiple myeloma used at our institution. There are minimal differences between each regimen when toxicities are managed appropriately. Disclosures Richardson: Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Mo:Celgene/BMS: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Cyclophosphamide, Thalidomide, and Dexamethasone as Initial Therapy for Patients With Newly Diagnosed Multiple Myeloma in a Middle-Income Country: 7-Year Follow-Up

2021 ◽  
pp. 1199-1205
Author(s):  
Jule Vasquez ◽  
Rossana Ruiz ◽  
Karina Aliaga ◽  
Fernando Valencia ◽  
Marco Villena ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Low Income ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
Staging System ◽  
Complete Response ◽  
Common Adverse Event ◽  
Newly Diagnosed ◽  
Middle Income

PURPOSE Major progress has occurred in multiple myeloma (MM) treatment in recent years, but this is not seen in low- and middle-income countries. MATERIALS AND METHODS We retrospectively assessed the efficacy and safety of cyclophosphamide, thalidomide, and dexamethasone (cyclophosphamide 400 mg/m2 for 5 days, thalidomide 100 mg once daily, if tolerated, and dexamethasone 40 mg once weekly; in 28-day cycles) in patients with newly diagnosed MM treated at our institution between April 2008 and December 2012. Survival outcomes were estimated by the Kaplan-Meier method. RESULTS Fifty-nine patients were found to meet the selection criteria. Median age was 56 years (27-78). Fifty-nine percent (n = 35) were male. International Staging System three was found in 24%. The median number of treatment cycles was 11 (range 4-12). After a median of 81-month follow-up (range 5-138 months), the overall response rate was 69.5%. The complete response and very good partial response were 5% and 32%, respectively. Median progression-free survival (PFS) was 35 months (95% CI, 18 to 41). The 3-year PFS was 47.4% (95% CI, 34.5 to 59.6) and 5-year PFS was 24.9% (95% CI, 14.4 to 36.9). The median of overall survival (OS) was 81 months (95% CI, 33 to not reached). The 3-year OS was 63.4% (95% CI, 49.2 to 74.6), and 5-year OS was 57.5% (95% CI, 43.2 to 69.4). The most common adverse event was neutropenia (grade 3 and 4, 30.5%). Out of 23 patients eligible for stem-cell transplantation, 10 (43.5%) proceeded with autologous transplantation. Treatment-related deaths occurred in four patients (6.7%). CONCLUSION Cyclophosphamide, thalidomide, and dexamethasone achieves good response rates with tolerable toxicity, especially in patients age 65 years or younger representing a feasible approach for patients with MM in low-income health care settings.

scholarly journals Correlation Analysis Between Serum Lactate Dehydrogenase and Prognosis in Old New Diagnosed Multiple Myeloma Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5637-5637
Author(s):  
Yahui Yuan ◽  
Yan Gu ◽  
Xiaoyan Qu ◽  
Qinglin Shi ◽  
Hua Bai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Lactate Dehydrogenase ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Staging System ◽  
Serum Lactate ◽  
Stage Ii ◽  
Stage Iii ◽  
Serum Lactate Dehydrogenase

Abstract 【Abstract】 Objective Multiple myeloma (MM) is a kind of plasma cell malignancy tumor with larger heterogeneity. Patient's survival varies greatly. This study retrospectively analyzed serum lactate dehydrogenase (LDH) in 107 cases of elderly MM patients, to discuss its correlation with other clinical indicators of MM and the prognostic significance. Methods 107 cases of elderly MM patients were selected from our hospital from July 2008 to January 2016 as the research objects, all of whom were above 60 years and were newly diagnosed. OLIPAS AU5400 fully automatic biochemical analyzer was used to assay serum LDH concentration, and prognosis analysis was carried out combined with patients' clinical data. On this basis, 73 cases of MM patients were given R-ISS staging. Results At primary diagnosis, about 9.4% patients had increased LDH (10/107), with the median follow-up time of 15 (1-88.5) months. Median overall survival (OS) was 52.5±6.9 months in normal LDH group, while 15.5±5.2 (months) in elevated LDH group, and there were statistically significant differences (p<0.001); Median progression free survival (PFS) was 24.0±3.5 months in normal LDH group, while 12.0±10.5 monthsin elevated LDH group, and there were statistically significant differences (p=0.008). Multiple factors analysis showed that LDH was an independent prognosis factor of elderly MM. Median OS of patients was 44 and 72 months (p=0.820) with stage II and stage III of ISS staging, while median PFS was 23 and 22 months (p=0.963); Median OS of patients was 44 and 22.5 months (p=0.308) with stage II and stage III of R-ISS staging, while median PFS was 24 and 14 months (p=0.105). Conclusions LDH is one of the important indicators for prognostic judgment of elderly MM patients. R-ISS staging based on LDH level is superior to the ISS staging system in prognostic judgment. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy of Upfront Daratumumab Combination Regimen in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3158-3158 ◽  
Author(s):  
Kyaw Zin Thein ◽  
Thura Win Htut ◽  
Myint Aung Win ◽  
Sriman Swarup ◽  
Anita Sultan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Novel Agents ◽  
Combination Regimen ◽  
Newly Diagnosed ◽  
Standard Risk

Introduction: Management of newly diagnosed multiple myeloma (NDMM), which accounts for 1% of all cancers, is an area in dire need of therapeutic innovation. In recent years, the introduction of novel agents is one of the major advances in the management of patients with NDMM, in both transplant- eligible and transplant- ineligible candidates. Studies have combined daratumumab, a human IgGκ monoclonal antibody that targets CD38 which is highly expressed on myeloma cells, with proteasome inhibitors and immunomodulatory agents-based regimens in the first-line treatment of NDMM. The purpose of our study is to explore and consolidate the efficacy of upfront daratumumab combination regimen in patients with NDMM. Methods: We systematically conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 2019. Phase III RCTs utilizing daratumumab in patients with newly diagnosed/ untreated multiple myeloma were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for progression-free survival (PFS) with 95% confidence interval (CI). Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) for overall response rate (ORR), including stringent complete response (sCR), CR and very good partial response (VGPR). Heterogeneity was assessed with Cochran's Q -statistic. Random effects model was applied. Results: Three phase III RCTs with a total of 2,528 patients with NDMMwere included.Studies compared daratumumab (D) + bortezomib (V) + melphan (M) + prednisone (P) vs VMP, D + lenalidomide (R) + dexamethasone (d) vs Rd, and DVd + thalidomide (T) vs VTd. The randomization ratio was 1:1 in all studies. The I2statistic for heterogeneity was 0, suggesting homogeneity among RCT. The pooled HR for PFS was statistically significant at 0.52 (95% CI: 0.44-0.61; P < 0.0001). The PFS benefit was observed in all ISS categories, types of immunoglobulin (Ig) and standard risk cytogenetic; ISS I cohort (HR, 0.55; 95% CI: 0.37- 0.82; P = 0.003), ISS II cohort (HR, 0.43; 95% CI: 0.33- 0.55; P < 0.0001), ISS III cohort (HR, 0.63; 95% CI: 0.48- 0.82; P = 0.0006), IgG cohort (HR, 0.56; 95% CI: 0.40- 0.77; P = 0.0003), non-IgG cohort (HR, 0.52; 95% CI: 0.28- 0.97; P = 0.04), and standard risk cytogenetic cohort (HR, 0.43; 95% CI: 0.35- 0.53; P < 0.0001). The pooled HR for PFS in high risk cytogenetic cohort was not statistically significant at 0.76 (95% CI: 0.53- 1.10; P = 0.15). The pooled RR for ORR was 1.13 (95% CI: 1.01-1.26; P = 0.03), sCR was 2.02 (95% CI: 1.33-3.08; P = 0.001), CR was 1.46 (95% CI: 1.20-1.79; P = 0.0002),and VGPR was 1.01 (95% CI: 0.82-1.25; P = 0.93). The pooled RR for negative minimal residual disease (MRD) was 2.54 (95% CI: 1.24-5.20; P = 0.01). Conclusions: Upfront combination regimen with daratumumab significantly improved PFS, ORR, sCR and CR along with negative MRD, compared to control arm in patients with NDMM. The improvement in PFS was noted across all subgroups except in high-risk cytogenetic group. More randomized studies are required to explore further novel agents and to formulate optimal combination regimen to improve survival in this high-risk cytogenetic subset. Disclosures No relevant conflicts of interest to declare.

Prognostic impact of kinetics of circulating plasma cells before and after induction therapy in newly diagnosed multiple myeloma patients undergoing early transplantation.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8020-8020
Author(s):  
Rajshekhar Chakraborty ◽  
Eli Muchtar ◽  
Angela Dispenzieri ◽  
Martha Lacy ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Induction Therapy ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Color Flow ◽  
Course Of Illness ◽  
The Impact

8020 Background: Circulating plasma cells (CPCs) at diagnosis, prior to transplant and at relapse have a negative prognostic impact on survival in multiple myeloma (MM). However, the impact of changes in CPCs along the course of illness has not been defined. Methods: We evaluated 247 patients with newly diagnosed MM (NDMM) undergoing early autologous stem cell transplantation (ASCT) in the era of novel agents (2007 to 2015), who had serial evaluation of CPCs at diagnosis and pre-ASCT by 6-color flow cytometry. Results: The median age at transplant was 62 years.A total of 117 (47%) patients had no detectable CPCs at both time points (CPC-/-), 82 (33%) had CPCs at diagnosis followed by complete eradication after induction therapy (CPC+/-) and 48 (19%) had detectable clonal CPCs at transplant, with persistence of cells (CPC+/+; n=45) or emergence of new CPCs (CPC-/+; n=3) after induction. The incidence of t(11;14) by iFISH was lower in the CPC-/- group (19%) compared to CPC+/- (29%) and CPC +/+ or -/+ (39%) groups ( p=0.033). Conversely, the incidence of hyperdiploidy was significantly higher in patients with CPC-/-, compared to those with CPC+/- and CPC+/+ or -/+ (64%, 44% and 39% respectively; p=0.005). The rate of post-ASCT stringent complete response was 32% in the CPC-/- group, 30% in CPC+/- group and 12% in CPC+/+ or -/+ group ( p=0.018). At a median follow-up of 58 months from ASCT, the median progression-free survival (PFS) from transplant in the 3 respective groups was 30, 24 and 14 months and the 5-year overall survival (OS) rates were 83%, 70% and 43% ( p<0.001 for both comparisons). On a multivariate analysis, using CPC-/- group as the comparator, PFS and OS was significantly inferior in CPC+/- (RR 1.6; p=0.020 and RR 2.7; p=0.008 for PFS and OS respectively) and CPC +/+ or -/+ groups (RR 2.9; p<0.001 and RR 5.8; p<0.001 for PFS and OS respectively). Conclusions: Clonal CPCs are detectable in more than 50% of newly diagnosed MM patients undergoing upfront ASCT. Monitoring for CPCs before initiation of induction therapy and before ASCT by 6-color flow cytometry is highly predictive of outcome in NDMM and should be incorporated into prospective clinical trials.

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