scholarly journals Abnormal Metaphase Cytogenetics Adds to Currently Known Risk-Factors for Venous Thromboembolism in Multiple Myeloma: Derivation of the PRISM score

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Rajshekhar Chakraborty ◽  
Lisa Rybicki ◽  
Jason Valent ◽  
Alex V. Mejia Garcia ◽  
Beth M. Faiman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
High Risk ◽  
Research Funding ◽  
Treatment Initiation ◽  
Newly Diagnosed ◽  
Prism Score ◽  
C Statistic ◽  
The Impact ◽  
Disease Specific

Background: Prevention and management of venous thromboembolic events [VTE] is an important component of supportive care in newly diagnosed multiple myeloma [MM], especially in the era of immunomodulatory drugs [IMiDs]. Recently, two validated risk assessment models [RAMs], SAVED and IMPEDE-VTE, were developed to identify patients at high risk of VTE. However, these models have following limitations: (1) Patients were not uniformly treated in the era of contemporary MM therapy (2) Disease-specific variables were not available in the databases from which these scores were derived. Our primary aim was to develop a simple predictive model for VTE in MM using patient-specific, disease-specific, and treatment-specific variables. Our secondary aim was to assess the impact of VTE on overall survival [OS]. Methods: All consecutive patients with newly diagnosed MM treated at Cleveland Clinic from 1/1/2008 to 12/31/2018 were included in our analysis. The primary objective was to identify baseline variables associated with VTE within 12 months of treatment initiation. Candidate variables included those in IMWG, SAVED, and IMPEDE-VTE models as well as additional risk-factors from literature review in MM and cancer-associated VTE. Stepwise selection with variable entry criterion of p<0.20 and a variable retention criterion of p<0.05 was used to identify significant factors on multivariable analysis [MVA]. RAM was developed by subtracting 1 from the hazard ratio of a potential variable, rounding to the nearest 0.5, and multiplying by 2 to obtain a whole number. The impact of VTE on OS was assessed with landmark analysis. Results: A total of 934 patients with newly diagnosed MM and available data on VTE occurrence were considered for inclusion. We excluded patients with VTE within 6 months before starting therapy [n=5] and patients on therapeutic anticoagulation or receiving >1 prophylactic regimen [n=146], resulting in a total of 783 patients for model development. The most common induction regimen was bortezomib [V]-lenalidomide [R]-dexamethasone [VRD; 41%], followed by VD [22%], RD [20%], V-cyclophosphamide-dexamethasone [VCD; 11%], and others [7%]. Median age at treatment initiation was 63 years [range, 22-91], 55% were males, and 20% were Blacks. ISS stage III disease was present in 32%, high-risk FISH in 23%, abnormal metaphase cytogenetics in 18%, and serum creatinine >2 mg/dl in 19% of patients. Notably, 76% had received a dexamethasone dose of 120-160 mg/cycle, with only 5.9% started on a higher dose [>160 mg/cycle]. The most common thromboprophylaxis agent was aspirin [60%], followed by low molecular weight heparin [LMWH; 3.8%]; 37% of patients received no thromboprophylaxis. Erythropoietin and intravenous immunoglobulin were used in 2.9% and 1.2% of patients respectively. Median time to VTE from treatment initiation was 3.2 months. Cumulative incidence of VTE at 6 and 12 months was 8.2% [95% CI, 6.6-10.1] and 11.5% [95% CI, 9.5-13.6] respectively. Factors significantly associated with development of VTE on MVA were combined to develop the PRISM score [Table 1]: Prior VTE history [HR 5.06; 8 points], Black Race [HR 1.71; 1 point], IMiD use [HR 2.17; 2 points], Surgery within 3 months [HR 3.44; 5 points], and abnormal Metaphase cytogenetics [HR 2.10; 2 points]. The theoretical score range is 0-18, with a HR of 1.28 per 1-point increase in score [c-statistic 0.62]. Internal bootstrap validation including 1,000 samples showed a c-statistic of 0.62 [IQR, 0.60-0.64]. Using three risk groups by recursive partitioning analysis, 17.8%, 74%, and 8.1% belonged to low [0], intermediate [1-6], and high-risk [>6] groups respectively. The 12-month cumulative incidence of VTE in the 3 respective groups were 2.7%, 10.8%, and 36.5% [Figure 1]. Occurrence of VTE in the first 12 months was not associated with worse OS on landmark analysis at 3, 6, 9, and 12 months. Conclusion: We have developed and internally validated a RAM for VTE in MM in the context of contemporary MM therapy including disease-specific variables. Studies of external validation and comparison with existing RAMs are warranted. The PRISM Score could be used to identify high-risk patients for thromboprophylaxis. Figure Disclosures Valent: Amgen Inc.: Other: Teaching, Speakers Bureau; Takeda Pharmaceuticals: Other: Teaching, Speakers Bureau; Celgene: Other: Teaching, Speakers Bureau. Khouri:Sanofi Genzyme: Other: Advisory Board. Anwer:Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Khorana:Pharmacyclics: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Leap: Research Funding; Bayer: Honoraria; Janssen: Honoraria; Merck: Research Funding; Array: Other: Research funding (to institution); BMS: Honoraria, Research Funding.

scholarly journals Outcomes with early response to first-line treatment in patients with newly diagnosed multiple myeloma

2019 ◽  
Vol 3 (5) ◽  
pp. 744-750 ◽  
Author(s):  
Nidhi Tandon ◽  
Surbhi Sidana ◽  
S. Vincent Rajkumar ◽  
Morie A. Gertz ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Light Chain ◽  
Progression Free Survival ◽  
Early Response ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Best Response ◽  
Light Chain Disease ◽  
The Impact

Abstract We evaluated the impact of achieving a rapid response in 840 newly diagnosed multiple myeloma patients from 2004 to 2015. Rates of very good partial response (VGPR) or better were 29% (240/840) after 2 cycles of treatment, 42% (350/840) after 4 cycles of treatment, and 66% (552/840) as best response. Early responders after 2 cycles of treatment had higher rates of light chain disease, anemia, renal failure, International Staging System (ISS) stage III disease, and high-risk cytogenetics, especially t(4;14), and were more likely to have received triplet therapy and undergo transplant. Median progression-free survival (PFS) and overall survival (OS) were not different among patients with ≥VGPR and <VGPR after 2 cycles (PFS, 28 vs 30 months, P = .6; OS, 78 vs 96 months, P = .1) and 4 cycles (PFS, 31 vs 29 months; OS, 89 vs 91 months, P = .9), although both were improved, with ≥VGPR as best response (PFS, 33 vs 22 months, P < .001; OS, 102 vs 77 months, P = .003). On multivariate analysis stratified by transplant status, achievement of ≥VGPR after 2 cycles was not associated with improved PFS (hazard ratio [95% confidence interval]; transplant cohort, 1.1 [0.7-1.6]; nontransplant cohort, 1.2 [0.8-1.7]) or OS (transplant cohort, 1.6 [0.9-2.9]; nontransplant cohort, 1.5 [1.0-2.4]). Covariates in the model included high-risk cytogenetics, ISS stage III, triplet therapy, creatinine ≥2 mg/dL, light chain disease, and age. Although patients with high-risk disease are more likely to achieve early response, a rapid achievement of a deep response by itself does not affect long-term outcomes.

Meta-Analytic Summary of the Burden of Pain and Fatigue in Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5967-5967
Author(s):  
Peter C. Trask ◽  
Mark Atkinson ◽  
Bhumi Trivedi ◽  
Andrew Palsgrove ◽  
William Benton Jones ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Sensitivity Analysis ◽  
Research Funding ◽  
Meta Analysis ◽  
Clinical Group ◽  
Common Symptom ◽  
Newly Diagnosed ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
The Impact

Abstract Aims: Multiple myeloma (MM) is a hematologic malignancy of plasma cells. Bone disease is a characteristic symptom of MM, and pain is one of its most distressing features. Anemia is also a common symptom and is manifested as fatigue and tiredness among MM patients. We conducted a systematic review and meta-analysis of the EORTC QLQ-C30 pain and fatigue scales in two clinical MM populations (one with newly-diagnosed MM and a second undergoing medical management with re-emergent or advanced myeloma) to more precisely quantify the burden of pain and fatigue in MM. Methods: Studies assessing pain and fatigue in MM were identified through a search of specific terms in the medical-subject headings and keywords in PubMed. Inclusion criteria were English-language studies published between January 1, 1996, and July 1, 2014; diagnosis of MM; and availability of data on pain and/or fatigue as measured by the EORTC QLQ-C30. Full-text articles from germane abstracts were retrieved for eligibility assessment, and 27 articles were selected for inclusion in the analysis. Two groups of peer-reviewed articles were created: one consisting of publications that focused on newly-diagnosed MM and the other consisting of articles involving MM patients with advanced conditions, including those who had a disease recurrence or were receiving autologous bone marrow transplantation. The mean values and standard deviations (SDs) were recorded across all publications irrespective of sex, age, and stage of illness. Of the 27 studies, 17 did not report standard error (SE) or SD values associated with EORTC QLQ-C30 pain and fatigue scales. These missing values were estimated using the overall average of SDs for that scale observed across all studies within the publication group (either newly-diagnosed or recurrent/advanced disease). A sensitivity analysis was conducted to compare the pooled mean and SEs associated with results obtained with and without the SD imputation procedure. The means and SDs from the two sets of publications were entered into Comprehensive Meta-analysis™ with both scales (pain or fatigue) and existing or imputed SDs as grouping variables. The summary means and confidence intervals for each scale by clinical group were computed by weighting the individual studies by sample size and were statistically summarized based on a fixed-effect model. Results: The EORTC QLQ-C30 fatigue and pain scales range from 0-100 with higher scores indicating greater symptoms (i.e., more fatigue and pain). The overall mean across the 27 publications was 47.1 for fatigue and 48.2 for pain for MM patients compared to scores of 25.0 and 16.9 for a general population. The results of the sensitivity analysis indicated that estimation of the SDs for those studies missing the statistic did not have a significant effect on the summary mean estimate. In most cases, the inclusion of additional means with estimated SDs reduced the summary SE estimate associated with the summary mean. Overall, the scores for fatigue and pain across research articles involving newly-diagnosed patients (fatigue=48.5 and pain=49.1) were statistically higher (indicating worse pain and fatigue) than among patients who were recurrent or receiving more aggressive treatments (fatigue=39.9 and pain=38.7). Conclusions: The burden of pain and fatigue in MM is substantial and is different between newly-diagnosed and more advanced MM patients. Pain and fatigue can be easily quantified using standardized health-related quality of life instruments. Pivotal clinical trials in MM need to assess the impact of novel treatments on pain and fatigue. Disclosures Trask: Sanofi: Employment. Atkinson:Sanofi: Research Funding. Trivedi:Sanofi: Research Funding. Palsgrove:Sanofi: Research Funding. Jones:Sanofi: Employment. McHorney:Sanofi: Research Funding.

scholarly journals Hypercoagulability Biomarkers in a New Score Linked to Treatment Resistance for Multiple Myeloma Patients. the Roadmap-MM Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1913-1913
Author(s):  
Loula Papageorgiou ◽  
Despina Fotiou ◽  
Patrick Van Dreden ◽  
Laurent Garderet ◽  
Meletios A. Dimopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Blood Coagulation ◽  
Research Funding ◽  
Thrombin Generation ◽  
Treatment Initiation ◽  
Treatment Resistance ◽  
Poor Response ◽  
Disease Stage ◽  
Newly Diagnosed ◽  
Healthy Individuals

Background: Research has focused on the implications of platelet, endothelial cell and blood coagulation activation in the risk of venous thromboembolism (VTE) in patients with multiple myeloma (MM). The reciprocal interaction between cancer cells and blood coagulation renders biomarkers of hypercoagulability as potential candidates for the evaluation of resistance to treatment in patients with newly diagnosed multiple myeloma (NDMM). Aims: The aim of the current analysis of the ROADMAP-MM study was to identify among a large number of hypercoagulability biomarkers in NDMM patients the most clinically relevant for the inclusion in treatment-resistance assessment tools. Methods: The ROADMAP-MM-CAT study (NCT03405571) was an investigator initiated, prospective, non-interventional trial. Newly diagnosed, treatment naïve symptomatic patients with multiple myeloma (based on 2014 IMWG Criteria) (n=144) were enrolled prior to treatment initiation and response to treatment was assessed at 3 months. Selected biomarkers , such as STA-Procoag-PPL®, factor VIIa factor V, antithrombin, fibrin monomers, thrombomodulin, free TFPI, D-Dimers, P-selectin, heparanase and thrombin generation (Calibrated Automated Thrombogram® and PPP-Reagent®) were measured. Results: At inclusion no patient had received any anti-myeloma treatment or thromboprophylaxis. Median age was 66.0±11.6 (36-86) years and 53% of the population was male. Regarding ISS disease stage: 32% were ISS-I, 23% ISS-II and 45% ISS-III. High risk cytogenetics [defined as presence of any of t(4;14), t(14;16) or del17p by FISH] were detected in 27% of the patients. In 32% of patients the treatment was immunomodulatory drug (IMiD) (90% lenalidomide and 10% thalidomide) and in 64% proteasome inhibitor (PI) based whereas 4% of patients received other regimens. Before any treatment administration - patients showed significantly increased levels of TFa, FVIIa, D-Dimers and FM and significantly shorter Procoag-PPL® as compared to the group of healthy individuals. Levels of P-selectin and TM were significantly lower in patients as compared to healthy individuals. Overall, thrombin generation was attenuated in patients compared to healthy individuals. Lag-time and ttPeak were significantly increased and Peak, MRI and ETP were significantly lower as compared to the group of healthy individuals At 3 months from treatment initiation, 23% (n=33) of the patients showed poor response or resistance to the anti-myeloma treatment. Among them, 7.6% (n=11) had progressive disease, 9.7% (n=14) had stable disease and 5.7% (n=8) had minor response. Among responders (n=111) 42.3 % (n=61) achieved PR and 34.7% (n=50) had VGPR. Multivariate logistic regression analysis for demonstrated that Procoag-PPL®≥41.7 versus <41.7 sec (OR=4.06, 95% CI: 1.59-10.38, p=0.003), D-Dimers ≥1.44 versus <1.44 μg/ml (OR=2.52, 95% CI: 1.06-6.01, p=0.037) and thrombin peak ≥181.66 versus <181.66 nM (OR=3.29, 95% CI: 1.17-9.26, p=0.024), were independently associated with poor response or resistance to anti-myeloma treatment Poor response/treatment resistance was associated with longer Procoag-PPL, higher D-dimer levels and higher thrombin's Peak. The new score had 84% sensitivity and 59% specificity to identify patients who showed treatment resistance at 3 months from treatment initiation. The AUC of the ROC analysis for the model was 0.75. Conclusions: Based on the evaluation of Procoag-PPL®, D-Dimers and Peak of thrombin generation, the prospective ROADMAP-MM-CAT study led to the derivation of an original risk assessment model for the identification of NDMM patients with poor response or resistance to the anti-myeloma treatment.. The identified biomarkers of hypercoagulability need to be correlated in future studies with established clinical prognostic parameters in multiple myeloma patients and then validated clinically within the context of prospective clinical trials in order to assess their role in clinical practice and in anti-myeloma treatment optimization. Disclosures Dimopoulos: Sanofi Oncology: Research Funding. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

scholarly journals EARLY Results of TOTAL Therapy 7 (TT7): High Response Rates of NEWLY Diagnosed High Risk Myeloma to Daratumumab

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4569-4569 ◽  
Author(s):  
Frits van Rhee ◽  
Sharmilan Thanendrarajan ◽  
Carolina D. Schinke ◽  
Jeffery R. Sawyer ◽  
Adam Rosenthal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Response Rates ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Early Results ◽  
Research Grant

Background. The TT approach has significantly improved the outcome of multiple myeloma (MM) by combining new drugs with a regimen that comprises induction, tandem autologous stem cell transplantation (ASCT), consolidation and maintenance. However, a group of 15% of patients with high risk multiple myeloma (HRMM) have derived little benefit despite similar response rates to induction chemotherapy and ASCT when compared to low risk MM. The poor outcome of HRMM is explained by early relapse post ASCT resulting in a short progression free survival (PFS) with only 15-20% of patients surviving long-term. Daratumumab (Dara) is a human IgG1k anti-CD38 monoclonal antibody that has shown favorable results in early single-arm studies and more recently in phase III studies for relapsed/refractory and newly diagnosed MM. In TT7, we introduced Dara during all phases of therapy, including immune consolidation early post ASCT, to improve responses rate and PFS in HRMM. Methods. Patients had newly diagnosed HRMM as defined by high risk cytogenetic abnormalities, presence of extramedullary disease, >3 focal lesions on CT-PET, elevated LDH due to MM, or ISS II/III with cytogenetic abnormality. Dara (16mg/kgx1) was added to induction with KTD-PACE (carfilzomib, thalidomide, dexamethasone; and four-day continuous infusions of cisplatin, doxorubicin, cyclophosphamide, etoposide). Conditioning for tandem autologous stem cell transplantation (ASCT) was with fractionated melphalan (50mg/m2x4) (fMEL) based on prior observations that patients with adverse cytogenetics fare better with fMEL rather than single high dose MEL200mg/m2.In the inter tandem ASCT period immunological consolidation with Dara (16mg/kg) alone for 2 doses was followed by Dara (16mg/kg) on day 1 combined with K (36mg/m2) and D (20mg) weekly for 2 cycles. DaraKD was administered to avoid treatment free periods allowing for myeloma regrowth. The 2nd ASCT was followed by further immunological consolidation with Dara (16mg/k) for 2 doses, and maintenance therapy for 3 yrs with 3-months block of alternating Dara-KD (dara 16mg/kg day 1; K 36mg/m2 and dex 20mg weekly) and Dara-lenalidomide (R)D (dara 16mg/kg day 1; R 15mg day 1-21 q28 and D 20mg weekly). Results. TT7 enrolled 43 patients thus far. The median follow-up was 11 months (range: 1-22). The median age was 61 yrs (range 44-73). Sixteen patients were ≥65 yrs (37.2%). A mean of 29.4x106 CD34+ cells/kg (range: 4.6-86.4) were collected. 36 patients completed ASCT #1 (83.7%) and 18 (41.9%) ASCT #2, whilst 14 patients have proceeded to the maintenance phase. R-ISS II/III or metaphase cytogenetic abnormalities were present in 85.1 and 58.1% of patients, respectively. Elevated LDH or >3FL on CT-PET were noted in 30 and 41.8%. The 1-yr cumulative incidence estimates for reaching VGPR and PR were 87 and 83%, respectively. A CR or sCR was achieved in 68 and 46%. The 1-yr estimates of PFS and OS were 91.6 and 87.2%. 40 subjects are alive, whilst 5 progressed on study therapy and 3 subsequently died. 38 patients are progression free at the time of reporting. Dara was well-tolerated and no subjects discontinued therapy due to dara-related side effects. The CR and sCR rates compared favorably to the predecessor HRMM TT5 protocol where CR and sCR rates were 59 and 27%. Conclusion. The early results of TT7 point to increased response rates of HRMM to a dara-based TT regimen with especially higher rates of CR and sCR. Longer follow-up is required to determine if these early results translate into superior PFS and OS. Figure Disclosures van Rhee: Karyopharm Therapeutics: Consultancy; Kite Pharma: Consultancy; Adicet Bio: Consultancy; Takeda: Consultancy; Sanofi Genzyme: Consultancy; Castleman Disease Collaborative Network: Consultancy; EUSA: Consultancy. Walker:Celgene: Research Funding. Morgan:Amgen, Roche, Abbvie, Takeda, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Other: research grant, Research Funding. Davies:Amgen, Celgene, Janssen, Oncopeptides, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Consultant/Advisor; Janssen, Celgene: Other: Research Grant, Research Funding.

Medullary Abnormalities in Appendicular Skeletons Detected With18F-FDG PET/CT Predict an Unfavorable Prognosis in Newly Diagnosed Multiple Myeloma Patients With High-Risk Factors

2019 ◽  
Vol 213 (4) ◽  
pp. 918-924 ◽  
Author(s):  
Yoshiaki Abe ◽  
Kentaro Narita ◽  
Hiroki Kobayashi ◽  
Akihiro Kitadate ◽  
Masami Takeuchi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
High Risk ◽  
Fdg Pet ◽  
Newly Diagnosed ◽  
High Risk Factors ◽  
Pet Ct ◽  
Fdg Pet Ct

The impact of novel induction regimens on transplant outcome in newly diagnosed multiple myeloma after controlling for high-risk FISH cytogenetics.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 8033-8033
Author(s):  
Rajshekhar Chakraborty ◽  
Eli Muchtar ◽  
Shaji Kumar ◽  
Francis Buadi ◽  
David Dingli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Newly Diagnosed ◽  
Fish Cytogenetics ◽  
Transplant Outcome ◽  
The Impact

Early Infection Risk in Newly Diagnosed Multiple Myeloma Patients in the Modern Era

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3794-3794
Author(s):  
Ryan Stevenson ◽  
Diane M. Carpenter ◽  
Adnan Khan ◽  
Raleigh Fatoki ◽  
Sumanth Rajagopal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
High Risk ◽  
Race And Ethnicity ◽  
The United States ◽  
Newly Diagnosed ◽  
Infection Rates ◽  
Community Based ◽  
The Past ◽  
Standard Risk

Abstract Background: Multiple myeloma (MM) is the second most common hematologic malignancy, with an estimated 30,000 new cases in the United States annually. Advances in management of MM over the past 20 years have significantly improved outcomes, but MM continues to be an incurable disease. Infections continue to be a major cause of morbidity and mortality, with a high proportion of MM patient developing infections within the first 3 months of diagnosis. There have been limited data on infection rates in MM patients in community-based oncology setting over the past two decades. This study looked to define infection rates and associated risk factors in newly diagnosed MM patients within 90 days of initial diagnosis. Methods: A retrospective, observational study was conducted on MM patients ages 18-89 newly diagnosed January 1, 2010-December 31, 2018 within Kaiser Permanente Northern California. Patients were required to have a minimum of one year of membership prior to MM diagnosis. SEER data was used to identify MM patients, and clinical data were extracted from the electronic health record. Bacterial, viral, and fungal infections were identified using ICD9/ICD10 codes. Baseline demographic and clinical characteristics from visit notes, laboratory and pathology results, and transplant data from utilization and claims data were analyzed to assess infection risks. High-risk cytogenetics was defined as notation of the following in pathology reports or oncology notes: add 1q, t(4:14), t(14:16), t(14:20), deletion of 17p. Bivariate analyses were conducted to assess differences across groups using the chi-squared test and the Wilcoxon-Mann-Whitney nonparametric test. Results: A total of 2030 newly diagnosed MM patients identified for this study. Median age at diagnosis was and n=828 (40.8%) of patients were female. Among this cohort, 522 (25.7%) had an infection within 90 days of MM diagnosis. The median age of patients having infections was 71 years (IQR 63-80), and the median age of those not having infections was 68 years (IQR 60-76, p&lt;0.001). The median Charlson Comorbidity Index (CCI) of patients having infections was 3 (IQR 1-5) and the median CCI of those not having infections was 2 (IQR 1-4, p&lt;0.001). Patients having hemoglobin &lt;10.0 g/dl were more likely to have infection than those having hemoglobin &gt;10.0 g/dl (30.4% vs. 23.6% respectively, p=0.011). Similarly, patients presenting with hypercalcemia (calcium &gt;11.0 mg/dL) were more likely to have infection (37.4% vs. 24.6% in patients having calcium &lt;11.0 mg/dL, p&lt;0.001) as were patients with creatinine clearance &lt;60.0 mL/min of those having &lt;60.0 mL/min vs. 20.7% of those having &gt;60.0 mL/min, p&lt;0.001). Patients having indicators of high-risk cytogenetics were less likely to have infections within 90 days of diagnosis compared to those with standard risk cytogenetics (21.1% vs 26.2% respectively, p=0.031). We did not detect significant differences across transplant eligible status within the first year after diagnosis (22.1% infection among transplant eligible vs. 26.6% among those who were not transplant eligible, p=0.059) nor across sex (27.3% among females vs. 24.6% among males, p=0.176). Additionally, no significant differences in infection were detected across race and ethnicity (24.0% infection among Asian patients, 26.4% among Black patients, 27.7% among Hispanic patients, 25.5% among White patients, and 14.3% among patients having unknown or other race and ethnicity, p=0.741). Conclusions: In this community-based oncology study, infection within 90 days of diagnosis continues to be a significant complication of multiple myeloma and these results are comparable to previous studies. Risk factors for infection include age, CCI, standard risk cytogenetics, anemia, hypercalcemia, and renal failure. Stem cell transplant, sex and ethnicity were not associated with increased risk for infection. Future analysis will include assessments of hospitalization and mortality associated with infection. This study illustrates the importance of further research looking at decreasing infection rates in multiple myeloma patients. Disclosures No relevant conflicts of interest to declare.

Final Analysis of MELISSE, a Large Multicentric Observational Study to Determine Risk Factors of Venous Thromboembolism in Patients with Multiple Myeloma Treated with Immunomodulator Drugs

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1235-1235 ◽  
Author(s):  
Xavier Leleu ◽  
Laurent Daley ◽  
Philippe Rodon ◽  
Cyrille Hulin ◽  
Charles Dauriac ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
High Risk ◽  
Incidence Rate ◽  
Research Funding ◽  
Final Analysis ◽  
Vte Prophylaxis ◽  
High Risk Patients ◽  
Increased Risk ◽  
Risk Patients

Abstract Abstract 1235 Background. Immunomodulator drugs (IMiDs) are associated with an increased risk of thromboembolic events (TE). Multiple Myeloma patients (MM) that can not benefit from novel agents, including IMiDs, only have 9 months survival. IMiDs must be stopped when TE occurs with the consequence of potential shortened life expectancy. MELISSE was designed to prospectively evaluate the incidence and risk factors of venous TE (VTE) associated with IMiDs in MM. We have presented the interim analysis of MELISSE at ASH 2010. A reduced incidence rate of early VTE was observed when a prophylaxis for VTE was started as compared to patients that had no prophylaxis. Interestingly, we also reported that most of the patients had received aspirin, while aspirin is not considered to exert any venous prophylactic effect. LMWH was primarily proposed to patients with high risk of TE according to physician's evaluation. We present the final analysis of MELISSE with updated results at 1 year. Method. A total of 524 MM treated with IMiDs-based therapy were included in 52 IFM centers. VTE prophylaxis was recommended prior to start IMiDs, the choice of which was left at the discretion of the investigator. Patients gave written informed consent according to the declaration of Helsinki. The physicians were to record the risk of VTE occurrence, categorized as low, moderate and high, based on guidelines and their own appreciation of the risk. Occurrence of any VTE was to be recorded along with the management of the event and the patient's outcome. The data were collected at entry in the study, and then after 4 and 12 months. Results. The median age was 70 years old, with 64.67% of patients >65 years old. Overall 36.0% had thalidomide-based and 64.0% had lenalidomide-based therapy, with 180 patients in first line and the remaining patients in 2nd and 3rd lines of therapy. The observed repartition of TE risk factors was as expected in a European population with myeloma. The risk of VTE was assessed as high in 14.2% patient and small or intermediate otherwise. Interestingly, approximately 70% of patients rated as low and intermediate risk received aspirin as a routine prophylaxis for VTE as compared to 20% in high risk patients. LMWH was primarily given to high risk patients, 45.8%. Surprisingly, 16.0% of patients had no VTE prophylaxis. Investigators recorded 29 (5.5% annual incidence rate) TE at 12 months, including 12 associated with PE. The incidence rate of TE was similar within the first 4 months (early occurrence, 3.5%) versus after 4 months (late, 2.5%). We have not identified any risk factor that would explain early versus late occurrence of VTE. Interestingly, the incidence of VTE was higher in patients that had no prophylaxis treatment, 8.5%, as compared to 4.4% and 5.9% in the LMWH and aspirin groups, respectively. There was no PE recorded in patients that were on LMWH prophylaxis. The VTE was equally breakdown across the 3 groups of risk factors. The bleeding adverse events were reported for 27 patients, mainly patients with aspirin. We isolated a model with 3 variables that independently predicted a higher risk to develop VTE in the multivariate model, and that comprised the male gender [OR 4.31 (95% CI 1.60 – 13.90)], the smoking habit [6.76 (1.73–22.42)] and the association to EPO [2.66 (1.04–6.58)]. Aspirin showed no significance, but with a p value at 0.55. The multivariate analysis is limited as certain subgroups with high risk factors might have received the optimal VTE prophylaxis, such as patients with bed rest and patients with prior history of VTE. These 2 groups rarely had aspirin. Survival data will be updated and presented at ASH 2011. Conclusion. This study further demonstrates that TE prophylaxis is required for MM treated with IMiDs-based therapy. There is a slight increase risk of VTE/PE with the use of aspirin as compared to LMWH, but a significant increase in bleeding events. Although we have identified risk factors of VTE in MM treated with IMiDs, for the first time, we could not identified VTE risk factors to guide investigators between LMWH and aspirin-based prophylaxis. The optimal dose and duration of LMWH remains to be determined. Disclosures: Leleu: LeoPharma: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; Roche: Research Funding; Amgen: Honoraria; Novartis: Research Funding. Daley:LeoPharma: Employment. Hulin:Janssen: Honoraria; Celgene: Honoraria. Lamblin:LeoPharma: Employment. Natta:LeoPharma: Employment.

Impact of Renal Impairment (RI) on Outcomes after Treatment (Tx) with Lenalidomide and Low-Dose Dexamethasone (Rd) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts): First Trial Results

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2112-2112
Author(s):  
Meletios A. Dimopoulos ◽  
Matthew C Cheung ◽  
Murielle Roussel ◽  
Ting Liu ◽  
Barbara Gamberi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Board Of Directors ◽  
Normal Renal Function ◽  
Research Funding ◽  
Failure Time ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Risk Of Death ◽  
The Impact

Abstract Background: Approximately 20–40% of pts with NDMM present with RI, which is associated with a negative impact on survival (Rajkumar, 2005). In the pivotal phase 3 FIRST trial (median follow-up 37 months [mos]), continuous Rd improved progression-free survival (PFS) vs. melphalan-prednisone-thalidomide (MPT) in elderly NDMM pts by 28% (25.5 vs. 20.7 mos; HR = 0.72; P < 0.01) (Facon, Blood 2013). Although 121 pts receiving continuous Rd are still on Tx, the interim overall survival (OS) analysis showed a 22% reduction in the risk of death in favor of continuous Rd vs. MPT (HR = 0.78; P = 0.02). The present analysis was conducted to determine the impact of RI on PFS, OS, and time to 2nd antimyeloma Tx (AMT) as clinical study outcomes. Methods: Pts were randomized to 3 Tx arms: continuous Rd until progression (n = 535); Rd for 18 cycles (72 weeks) (Rd18; n = 541); or MPT for 12 cycles (72 weeks) (n = 547). Enrolled NDMM pts were categorized according to their renal function: 24% had normal renal function (creatinine clearance [CrCl] ≥ 80 mL/min), 44% presented with mild RI (≥ 50 and < 80 mL/min), 23% had moderate RI (≥ 30 and < 50 mL/min), and 9% had severe RI (< 30 mL/min). Pts requiring dialysis were excluded. Lenalidomide starting dose was 25 mg QD for pts with normal renal function or mild RI, 10 mg QD for moderate RI, and 15 mg QOD for severe RI. Melphalan dose was reduced by 50% in pts with moderate or severe RI. The primary endpoint was PFS (continuous Rd vs. MPT); secondary endpoints were OS, overall response rate, time to response, duration of response, time to Tx failure, time to 2nd AMT, health-related quality of life, safety, and improvement in renal function from baseline. Improvement in RI was defined as shifts from baseline to most extreme post-baseline value of the calculated CrCl as a measure of renal function during the active Tx (N = 1484). Results: A PFS benefit favored continuous Rd vs. MPT irrespective of the degree of renal function (Table 1): there was a benefit in pts with normal renal function (HR = 0.72 (0.51–1.02); P = 0.06), and better in pts with mild RI (HR = 0.79 (0.62–1.00); P = 0.05) and moderate RI (HR = 0.62 (0.45–0.85); P < 0.01). A PFS benefit was also seen with continuous Rd vs. Rd18 (a secondary comparison) in pts with mild RI and moderate RI (P < 0.01 for both). An interim OS benefit with continuous Rd vs. MPT was observed in most renal subgroups. Similar results were observed between Rd18 and MPT in terms of PFS or interim OS in any of the renal subgroups. Continuous Rd, compared with Rd18 or MPT, extended time to 2nd AMT in most renal groups except severe RI (CrCl < 30mL/min) (Table 2). Improvement in RI was observed more frequently in pts treated with continuous Rd than those with Rd18 or MPT: improvement of mild RI, 48%, 43%, and 48%, respectively; of moderate RI, 67% 61%, and 62%; and of severe RI, 64%, 59%, and 56%. Overall, < 5% of pts in any Tx group experienced a worsening in renal function status during Tx (continuous Rd 2.2%; Rd18 2.8%; MPT 2.7%). The most common grade 3–4 adverse events (AEs) for these Txs were anemia, neutropenia, thrombocytopenia, deep-vein thrombosis/pulmonary embolism (DVT/PE), and peripheral sensory neuropathy (Table 3). Tx discontinuation due to AEs increased in pts with moderate and severe RI, regardless of the type of Tx (Table 3). Conclusions: PFS, OS (at interim analysis), and time to 2nd AMT outcomes generally improved continuous Rd vs. Rd18 or MPT in transplant-ineligible NDMM pts with normal renal function, and in those with mild or moderate RI. The small number of pts in the severe RI group precluded a meaningful conclusion. Continuous Rd was generally well tolerated and renal function improved in the majority of pts during Tx with continuous Rd vs. Rd18 or MPT. Disclosures Dimopoulos: Celgene Corporation: Consultancy, Honoraria. Off Label Use: Lenalidomide used in newly diagnosed multiple myeloma patients. Roussel:Celgene: Consultancy, Lecture fees Other, Research Funding. van der Jagt:Celgene Corporation: Research Funding. Jaccard:Celgene Corporation: Honoraria, Research Funding. Tosikyan:Celgene: Consultancy. Karlin:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bensinger:Celgene Corporation: Consultancy, Research Funding. Schots:Celgene: Research Funding. Chen:Celgene Corporation: Employment. Marek:Celgene Corporation: Employment, Equity Ownership. Ervin-Haynes:Celgene Corporation: Employment. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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