Hemostasis in Newly Diagnosed Multiple Myeloma Patients before and after Induction Therapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5388-5388
Author(s):  
Evdokia S. Urnova ◽  
Larisa P. Mendeleeva ◽  
Olga S. Pokrovskaya ◽  
Marina A. Gracheva ◽  
Eduard G. Gemdzhian ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Stage Iii ◽  
Normal Rate ◽  
Newly Diagnosed ◽  
Complex Disorders ◽  
Significant Difference ◽  
Before And After ◽  
The Status ◽  
D Dimer

Abstract Background: Course of multiple myeloma (MM) is associated with hemostatic disorders that can lead to bleeding or thrombosis. According to previous studies the most risky period of time for thrombotic complication is the first year after diagnosis. Aims: The study was aimed to analyze of hemostasis conditions in newly diagnosed (ND) MM patients (pts) and to compare their initial status with the status after induction therapy (IT) and with the status of healthy volunteers (HV). Patients and Methods: 17 pts with ND MM: 10 males, 7 females at the age of 26-72 (median age - 54) were involved in the study. The distribution of the stages among the participants according to Durie-Salmon system: stage I - 1 pts, stage II - 5 pts, stage III - 8 pts, stage III in 8 pts. Immunochemistry variants: IgG - 11 pts, IgA - 2 pts, MM B-J - 4 pts. Average paraprotein (PP) level was 34g/L (0,8 - 78). HV group consisted of 26 persons without serious diseases, 40 - 70 y.o., (median age 50). Hemostasis analysis was taken place twice: before and after the IT which included 4-8 bortesomib-containing cycles (PAD, VCD, VD). After the IT 6 pts achieved CR, 5 pts - VGPR, 4 pts - PR and 1pt was resistant. Average value of PP decreased to 8 (0,1 - 29,7). Routine tests: activated partial thromboplastin time (APTT, normal rate 25-38 sec), international normalized ratio (INR, normal rate 0.85-1.15), D-dimer concentration (normal rate 0-500 mkg/l). Two global tests: thrombin generation test by using endogenous thrombin potential (ETP, normal rate 760-1450 nM*min) and thrombodinamics (TD), characterized by the initial clot growth velocity (Vi, normal rate 36-56 um/min), stationary velocity (Vst, normal rate 20-30um/min), and density of a fibrin clot measured by light scattering from clot (D, normal rate 16000 - 32000 conventional units). Hypocoagulability wasassessedby data APTT > 38 sec, INR> 1.15, ETP < 760 nM*min, Vi < 36 um/min, Vst < 20 um/min, D < 16000 cu. Hypercoagulability was considered in cases when APTT < 25 sec, INR < 0,85, D-dimer > 500 ng/ml, ETP > 1450 nM*min, Vi > 56 um/min, Vst > 30 um/min, D > 32000 cu. Statistics. Ðaired t-test and Pearson correlation coefficient (r) have been got with SAS 9.1. 95- percent CI has been used. Results: ND MM APTT evaluation demonstrated normal coagulation in 13pts and extended one in 4pts (48 sec [38-57]). INR was normal in 13 and increased in 4 cases (1.3% [1.2-1.5]). Increased concentration of D-dimer was revealed in 7pts (3810 ng/ml [350-7270]). ETP was normal in 12 and increased in 5 cases (1592 nM*min [1406-1779]). Vi was normal in 11 and increased in 6pts (62 um/min [58-65])). Vst was reduced in 1pts (15um/min), normal in 10pts and increased in 6pts (36um/min [28-44]). Density of clot was normal in 8 pts and decreased in 9pts (9769 UE [6379-13160]). (Tab. 1) After IT only 1 pt had elongated APTT (44sec), the results of the others were normal. INR was normal in all cases. D-dimer concentration was normal in 12pts and increased in 5pts, but this data was statistically less (1080ng/ml [500-1003]) than in ND MM. ETP was normal in 13pts, elevated in 4 pts (1604 nM*min [1099-2109]). Vi was normal in 12pts and increased in 4pts (61 um/min [57-65]). Vst was decreased in 2pts (13 and 14um/min), normal in 13pts and increased in 2 (32 and 43um/min). Density of clot became normal in 14pts, but clot remained not dense enough in 3 pts (9512 [13606-15779]). (Tab. 1) We found that inverse linear relationship between PP level and blood clot density was more significant in ND MM (Fig. 1, fig.2). Statistically significant difference was revealed between clot density in ND MM and pts in PR or CR and between them and HV (Fig. 3). Furthermore, a significant difference was identified between D-dimer concentration in ND MM pts and after IT (Fig. 4). Conclusions: MM pts have complex disorders of hemostasis characterized by a tendency to hyper- and hypocoagulation at the same time. In spite of an increased tendency to thrombosis confirmed by D-dimer, ETP, TD, pts are under risk of bleeding related to the formation of defective clot and elongated APTT. According to the obtained results one can assume that PP embedded in the clot and disorder its structure. However, further studies are needed to confirmthat assertion. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

scholarly journals Perubahan Status Koagulasi Pasien Kanker Padat Pasca Kemoterapi di Indonesia: Sebuah Studi Prospektif

2020 ◽  
Vol 7 (1) ◽  
pp. 2
Author(s):  
Noorwati Sutandyo ◽  
Lyana Setiawan
Keyword(s):  
Cancer Patients ◽  
Prospective Cohort ◽  
Stage Iv ◽  
Stage Iii ◽  
Solid Cancer ◽  
Significant Difference ◽  
Before And After ◽  
Coagulation Status ◽  
Stage Iv Cancer ◽  
D Dimer

Pendahuluan. Hiperkoagulasi merupakan faktor yang mendasari tingginya mortalitas akibat kejadian tromboemboli vena pada pasien kanker. Kemoterapi merupakan salah satu faktor yang diduga berkontribusi terhadap status hiperkoagulasi pada pasien kanker. Studi ini bertujuan untuk mengevaluasi perubahan status koagulasi yang ditandai dengan kadar D-dimer pada pasien kanker yang menjalani kemoterapi.Metode. Studi ini merupakan studi kohort prospektif di Pusat Kanker Nasional Indonesia yang melibatkan pasien kanker yang sudah terkonfirmasi melalui pemeriksaan histopatologi, dan memulai kemoterapi pada periode Mei hingga Juli 2018. Perubahan status koagulasi dinilai melalui kadar D-dimer plasma. Kadar D-dimer diukur sebelum dan 7 hari setelah kemoterapi. Analisis statistik menggunakan uji t berpasangan untuk menilai kemaknaan perubahan kadar D-dimer plasma sebelum dan setelah kemoterapi.Hasil. Sejumlah 89 pasien memenuhi kriteria inklusi, yang mana 74,2% adalah perempuan dan hampir separuh dari keseluruhan subjek terdiagnosis kanker payudara (44,9%). Mayoritas subjek (69,6%) terdiagnosis pada stadium III atau IV. Sejumlah 12,4% dari subjek mendapatkan kemoterapi berbasis cisplatin. Terdapat perbedaan yang bermakna antara kadar D-dimer sebelum dan setelah kemoterapi (p = 0,05). Studi ini juga menemukan perbedaan bermakna kadar D-dimer sebelum dan sesudah kemoterapi pada pasien kanker stadium III (t(35) = 2,48, p = 0,02) dan stadium IV (t(25) = 2,14, p = 0,04). Tidak terdapat perbedaan bermakna antara kadar D-dimer sebelum dan setelah kemoterapi pada pasien stadium I dan II. Analisis lanjutan berdasarkan kelompok kemoterapi menunjukkan bahwa terdapat perubahan kadar D-dimer yang bermakna pada kelompok yang mendapatkan kemoterapi cisplatin (t(10) = 2,31, p = 0,04), namun tidak pada kelompok yang mendapat kemoterapi non-cisplatin (t(77) = 1,50, p = 0,14).Simpulan. Terdapat perbedaan bermakna status koagulasi yang ditandai dengan kadar D-dimer 7 hari pasca mendapatkan kemoterapi, khususnya pada pasien kanker stadium III atau IV dan mendapatkan kemoterapi berbasis cisplatin. Kata Kunci: Cisplatin, kanker, kemoterapi, status koagulasiChange of Coagulation Status in Solid Cancer Patients Undergoing Chemotherapy in Indonesia: A Prospective Cohort StudyIntroduction. Cancer-associated hypercoagulability was an underlying factor of high mortality of cancer due to venous thromboembolism. Chemotherapy is proposed as one of the contributing factors of the hypercoagulable state. We aim to evaluate the change of coagulation status, which was marked by D-dimer level, in cancer patients receiving chemotherapy.Methods. This is a prospective cohort study in Indonesian national cancer center which involves all adult histologically-confirmed-cancer patients who started chemotherapy between May and July 2018. The coagulation status is assessed by plasma of D-dimer level. We measured D-dimer before chemotherapy and one week after chemotherapy. Paired t-test was performed to assess the significant difference in D-dimer levels before and after chemotherapy.Results. A total of 89 patients fulfilled the eligibility criteria, of whom 74.2% were female and almost half of total subjects (44.9%) were breast cancer patients. Majority of subjects (69.6%) were stage III or stage IV cancer. There were 12.4% of subjects received cisplatin-based chemotherapy. There was a marginally significant difference in plasma level of D-dimers before and after chemotherapy (p = 0.05). We also found significant differences between D-dimer level before and after chemotherapy in stage III patients (t(35) = 2.48, p = 0.02) and stage IV patients (t(25) = 2.14, p = 0.04). There was no significant difference between D-dimer level before and after chemotherapy in stage I and stage II patients. Subgroup analyses based on chemotherapy agents showed that there was significant D-dimer change in cisplatin-based chemotherapy subjects (t(10) = 2.31, p = 0.04), but not in non-cisplatin-based chemotherapy subjects (t(77) = 1,50, p = 0.14).Conclusion. Compared to before chemotherapy, there is a significant difference of coagulation status marked by plasma D-dimer level one week after chemotherapy, particularly in patients with stage III or stage IV cancer and in patients receiving cisplatin-based chemotherapy.

Bortezomib-Thalidomide-Dexamethasone Compared with Thalidomide-Dexamethasone as Induction and Consolidation Therapy Before and After Double Autologous Transplantation In Newly Diagnosed Multiple Myeloma: Results From a Randomized Phase 3 Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 42-42 ◽  
Author(s):  
Michele Cavo ◽  
Giulia Perrone ◽  
Silvia Buttignol ◽  
Elisabetta Calabrese ◽  
Monica Galli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Autologous Transplantation ◽  
Consolidation Therapy ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Significant Difference

Abstract Abstract 42 We prospectively compared thalidomide-dexamethasone (TD) with bortezomib-thalidomide-dexamethasone (VTD) as induction therapy before, and consolidation after, double autologous stem-cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma (MM). Three 21-d cycles of either VTD (V, 1.3 mg/m2 twice-weekly; T, 200 mg/d through d 1 to 63; D, 320 mg/cycle) or TD were given as induction therapy. Consolidation therapy comprised two 35-d cycles of VTD (V, 1.3 mg/m2 once-weekly; T, 100 mg/d through d 1 to 70; D, 320 mg/cycle) or TD. 474 patients randomized to the VTD (n=236) or TD (n=238) arm were analyzed on an intention-to-treat basis for response rate, PFS and OS. Centrally reassessed CR/nCR rate was significantly higher in the VTD compared with the TD arm after all treatment phases, including induction therapy (30% vs 10%, p<0.0001), double autotransplantation (54% vs 42%, p=0.008) and consolidation therapy (60% vs 44%, p=0.001). Best confirmed overall CR/nCR rate was 71% in the VTD arm compared with 52% in the TD arm (p<0.0001); the corresponding values for VGPR or better were 89% vs 72%, respectively (p<0.0001). To evaluate the role of consolidation therapy we performed a per-protocol analysis of 323 patients, 161 treated with VTD and 162 with TD. Overall, upgraded responses with VTD and TD as consolidation therapy were observed in 55% vs 37% of patients, respectively (p=0.01; OR:1.15-3.77). Furthermore, the probability to improve responses from less than CR before consolidation to CR after consolidation was 28% with VTD vs 15% with TD (p=0.02; OR:1.07-4.57) (p=0.003 using the Mc Nemar's test). Post-consolidation molecular detection of minimal residual disease was the objective of a substudy; detailed results are reported in a separate abstract. Briefly, both qualitative and quantitative analyses confirmed the statistically significant superiority of VTD over TD in effecting higher rates of molecular remissions and reducing the burden of residual myeloma cells after ASCT. Any grade 3–4 non-hematologic adverse events were 10% with VTD (peripheral neuropathy: 1.3%, skin rash: 0.6%) vs 12% with TD. With a median follow-up of 31 months, median PFS was 42 months in the TD arm and was not yet reached in the VTD arm (44-month projected rate: 61%) (HR: 0.62 [CI: 0.45–0.87], p=0.006). Superior PFS in the VTD vs TD arm was retained across patient subgroups with poor prognosis, including those with t(4;14) and/or del(17p). Randomization to VTD overcome the adverse influence of t(4;14) on PFS (40-month projected rates: 69% vs 67% according to the presence or absence of this abnormality, respectively; p=0.6). By the opposite, in the TD arm corresponding median PFS values were 24.5 vs 41.5 months, respectively (p=0.01). The small numbers of patients with del(17p) in both arms of the study precluded a statistical comparison with del(17p)-negative group. In a multivariate analysis, variables favorably influencing PFS were beta2-m lower than 3.5 mg/L (HR:0.47; p=0.000), absence of t(4;14) and/or del(17p) (HR:0.52; p=0.000), randomization to VTD arm (HR:0.57; p=0.002), attainment of at least VGPR (HR:0.50; p=0.009) and CR (HR:0.8; p=0.01). No statistically significant difference between the overall treatment protocols was seen in terms of OS, although curves seemed to initially diverge after 40 months (44-month projected rates: 84% vs 74% for VTD and TD arms, respectively). A multivariate analysis showed the independent role of absence of t(4;14) and/or del(17p) (HR:0.42; p=0.003), ISS stage1-2 (HR:0.49; p=0.02) and randomization to VTD (HR:0.53; p=0.04) in prolonging OS. When time-dependent CR entered the model, absence of t(4;14) and/or del(17p) and less advanced ISS stage retained their positive prognostic value; attainment of CR (strictly related to VTD randomization) was an additional favorable variable. In conclusion, in comparison with the TD arm of the study, 1) VTD induction emerges as a new standard of care for maximizing the degree and speedy of tumor reduction in preparation for ASCT; 2) VTD consolidation effected significantly higher rates of upgraded responses, including CR, and of molecular remissions; 3) double ASCT incorporating VTD as induction and consolidation therapy resulted in significantly longer PFS, a benefit confirmed in a multivariate regression analysis and maintained in the subgroup of patients with adverse cytogenetic abnormalities. Disclosures: Cavo: Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Use of bortezomib and thalidomide as induction therapy before, and consolidation after, autologous transplantation in newly diagnosed multiple myeloma. Baccarani:NOVARTIS: Honoraria; BRISTOL MYERS SQUIBB: Honoraria.

Phase 2 Study of Carfilzomib, Thalidomide, and Low-Dose Dexamethasone As Induction/Consolidation in Newly Diagnosed, Transplant Eligible Patients with Multiple Myeloma, the Carthadex Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1141-1141 ◽  
Author(s):  
Ruth Wester ◽  
Bronno van der Holt ◽  
Emelie Asselbergs ◽  
Mark van Duin ◽  
Sonja Zweegman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Induction Therapy ◽  
Research Funding ◽  
Fixed Dose ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Standard Risk

Abstract Introduction A phase 2 dose escalation trial of Carfilzomib in combination with Thalidomide and Dexamethasone (KTd) for induction and consolidation in newly diagnosed, transplant-eligible patients with multiple myeloma (MM). We report the results of 4 dose levels. Methods In this multicenter, open-label, phase 2 trial, transplant-eligible patients aged between 18 and 65 years with previously untreated symptomatic MM were included. Patients were treated with 4 cycles of escalating dose of Carfilzomib + fixed-dose thalidomide and dexamethasone (KTd) for induction therapy. The dose of Carfilzomib was 20 mg/m2 i.v. on days 1, 2 followed by 27 mg/m2 on days 8, 9, 15, 16 of cycle 1 and on days 1, 2, 8, 9, 15 and 16 of cycles 2 to 4. Thalidomide dose was 200 mg orally on days 1 through 28 and Dexamethasone 40 mg orally on days 1, 8, 15 and 22. Carfilzomib was escalated to 20/36 mg/m2 in cohort 2, to 20/45 mg/m2 in cohort 3 and to 20/56 mg/m2 in cohort 4. Induction was followed by stem cell harvest after Cyclophosphamide priming (2 to 4 mg/m2) and G-CSF. Hereafter patients received high-dose Melphalan (HDM, 200mg/m2) and autologous stem cell transplantation followed by consolidation treatment with 4 cycles of KTd in the same schedule except a lower dose of Thalidomide (50mg). The primary endpoint was response after induction therapy and overall, specifically complete response (CR) and very good partial response (VGPR). Secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS). Results All 111 patients with a median follow-up of 55, 42, 35 and 28 months, in cohorts 1 to 4, respectively were included in the analysis. Median age was 58 years. ISS stages I/II/III were 41%/34%/23%, respectively, R-ISS stages I/II/III/unknown were 23%/59%/9%/9%, respectively. Of 111 patients, 9 patients stopped treatment during/after induction, 8 patients after cyclophosphamide priming or HDM and 9 patients during consolidation because of toxicity (n=9), non-eligibility for further treatment (n=6), progression (n=5), refusal (n=2) or other reasons (n=4). Overall response rate for all cohorts was 95%. Response after induction was CR/sCR in 18% of patients, ≥ VGPR in 66% of patients, ≥ PR in 94% of patients. After HDM the CR/sCR rate increased to 31% and after consolidation to 64%. Responses between cohorts were in general comparable. See Table 1. Response based on risk status by ISS/FISH in either cohort and accumulated did not show a difference in CR/sCR rate after consolidation between standard-risk (67%) and high risk defined as t(4;14) and/or del17p and/or add1q and/or ISS3 (60%). OS at 30 months was comparable between standard risk and high risk, 91% versus 90%. PFS at 30 months for standard risk and high risk was 79% and 62%, logrank p=0.02 (HR=2.3, 95% CI=1.1-4.5). PFS at 30 months per cohort was 70% (95% CI, 55% to 81%), 70% (95% CI, 45% to 85%), 80% (95% CI, 56% to 92%) and 62% (95% CI, 32% to 82%) in cohorts 1,2, 3 and 4, respectively, and 71% (95% CI, 61% to 79%) in all patients. OS at 30 months per cohort was 90% (95% CI, 77% to 96%), 90% (95% CI, 66% to 97%), 95% (95% CI, 71% to 99%) and 88% (95% CI, 58% to 97%) respectively, and 91% (95% CI, 83% to 95%) in all patients. Gene expression profiling using the Affymetrix U133 Plus 2.0 GeneChips was performed on purified tumor cells for 49 patients. Using the prognostic classifier EMC92 a high-risk group of patients (16%) was identified versus standard risk (in terms of OS: logrank p=0.06 (HR=3.7, 95% CI=0.8-16.8), and in terms of PFS: logrank p=0.14 (HR=2.1, 95% CI=0.8-6.0)). Safety analysis for all 111 patients showed non-hematological grade 3 and 4 toxicity, mainly respiratory disorders (in 15%), GI disorders (13%) and skin lesions (10%). Toxicity between cohorts did not show a significant difference. Cardiac adverse events were limited and included heart failure (n=2 at 27 mg/m2), hypertension (n=2) and chest pain (n=1 at 45mg/m2). Conclusion Carfilzomib, thalidomide, dexamethasone (KTd) is an effective regimen, with increasing CR percentages following KTd consolidation. With escalated doses of Carfilzomib responses and toxicity were comparable to standard dose of 27 mg/m2. Disclosures Zweegman: Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Kersten:Celgene: Research Funding; Amgen: Honoraria. Minnema:Celgene: Consultancy; BMS: Consultancy; Amgen: Consultancy; Jansen Cilag: Consultancy. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria. Lokhorst:Genmab: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Broijl:Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Sonneveld:Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Celgene: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding.

scholarly journals Clinical Outcomes of Newly Diagnosed Multiple Myeloma Patients with Elevated Lactate Dehydrogenase Who Underwent Autologous Hematopoietic Stem Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4623-4623
Author(s):  
Susan Bal ◽  
Kwangmin Choi ◽  
Heather J. Landau ◽  
Daniel T. Starczynowski ◽  
Saulius K. Girnius
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Ecog Performance Status ◽  
Significant Difference ◽  
Cytogenetic Changes ◽  
Baseline Characteristics ◽  
Standard Risk ◽  
Elevated Lactate

Abstract Background Multiple Myeloma (MM) is a clinically heterogeneous disorder of clonal plasma cells. Elevated Lactate Dehydrogenase (LDH) has been shown to be an independent prognostic marker associated with drug resistance and shorter survival. Methods Utilizing data from the Multiple Myeloma Research Foundation (MMRF) CoMMpass database (IA12) which includes over 1000 newly-diagnosed MM (NDMM) patients with enriched tumor and matched constitutional samples analyzed using whole genome/exome and RNA sequencing, we identified patients with baseline LDH values. High LDH was defined as LDH greater than the upper limit of normal, (>4.68 microkatals/liter). We compared baseline characteristics and outcomes with autologous stem cell transplant (ASCT), based on LDH as categorical variable. We sought to determine if there is enrichment of high and standard risk cytogenetic changes when stratified by LDH. Results We identified 871 patients with NDMM who had baseline LDH values. 143 patients had high LDH and 728 patients had a normal baseline LDH. Consistent with prior reports, high LDH was associated with shortened survival, 660 days vs 795 days (p=0.02852) in patients with normal LDH. 385 patients underwent ASCT (High LDH N=44; Normal LDH N=341). Those with high LDH had an inferior OS when compared with those with normal LDH (median OS 800.5 vs 878.8 days, p=0.019). In order to understand this difference, we examined baseline characteristics. Of the 44 patients with high LDH who underwent ASCT, median age was 60 years and ECOG performance status was 1. 61.36% were females, 77% were Caucasian, 11% were African American. Induction therapy consisted of 4 drugs or more in 16%, 3 drugs in 61%, and 2 drugs in 23%. Bortezomib and immune modulating agents (IMIDS) were combined in 72%. In those who did not receive an IMID, a bortezomib-based induction was used in 16% and carfilzomib-based induction was used in 11%. 93.18% underwent transplant in the consolidative setting with a median time to transplant was 178 days. 21 of the 44 patients (47.72%) received post-transplant maintenance. 10/21(48%) patients received triplet therapy (5/10 - lenalidomide, bortezomib, dexamethasone), 8/21 (38%) patients received lenalidomide alone. The median duration of maintenance was 217 days. Of the 341 patients with normal LDH who underwent ASCT, the median age was age 61 years, ECOG performance status was 1. 41.34% were females, 79% were Caucasian, 13% African American. Induction therapy consisted of 4 drugs in 8%, 3 drugs in 64%, 2 drugs in 24%. Combined Bortezomib-IMID in 76.24%, carfilzomib-IMID based therapy in 6%, and bortezomib-non-IMID based in 9.67%. 94.7% underwent an upfront consolidative with median time to transplant 164 days. Post-transplant maintenance was given in 213/341 (62.4%) of patients, in whom triplet therapy was given to 41/213 (19.2%), doublet therapy to 34/213 (16%), 130/213 (61%) received single agent. 107/213 (50%) received lenalidomide alone and 19/213 (6%) received bortezomib alone. Median duration of maintenance 266 days. There was no statistically significant difference in race, performance status, drug class and number of drugs used in induction therapy, time to transplant, whether or not patients received maintenance as well as maintenance duration between the groups when stratified by LDH. Female gender was enriched in the high LDH group (hypergeometric test, p=0.009). We used hypergeometric tests to assess for enrichment of high and standard risk cytogenetic changes. Del(17p13) was significantly enriched (p=0.011) in the high LDH subset where there were no statistically significant difference in the presence of t(4;14) (p=0.16) and t(14;16) (p=0.21). There was no difference in good risk hyperdiploid structural changes between the 2 groups. Conclusion Elevated LDH was confirmed as a poor prognostic factor in MMRF CoMMpass cohort. Among patients who underwent ASCT, those with high LDH have inferior survival, possibly driven by the presence of del(17p13). Since clinical outcomes remain poor despite the use of novel effective therapies and early consolidation with AHCT in patients with high baseline LDH, this group represents an unmet need for alternative therapy. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Risk Stratified Tandem Vs Single Autologous Stem Cell Transplantation for Multiple Myeloma Yields Equivalent Survival

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 23-24
Author(s):  
Kevin Sing ◽  
Roy Sabo ◽  
James O'Bryan ◽  
Matthew Risendal ◽  
Catherine H Roberts ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Standard Of Care ◽  
High Dose ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Study Population ◽  
High Dose Melphalan ◽  
Standard Risk

The standard of care for patients with newly diagnosed multiple myeloma who are transplant eligible is induction therapy followed by conditioning with high dose melphalan and autologous hematopoietic cell transplant (HCT). While the value of a single HCT (S-HCT) is established in standard-risk myeloma (SRM), there is controversy about whether tandem transplantation would improve outcomes such as progression-free survival (PFS) or overall survival (OS) in high-risk myeloma (HRM) patients. In this IRB approved retrospective study, the records of 343 multiple myeloma patients, who were referred by community oncologists and underwent HCT at Virginia Commonwealth University from 2008 to 2015, were reviewed. Patients were classified into different disease risk groups and OS and PFS determined. HRM was defined as including at least one of the following prognostic factors at diagnosis: t(4;14), t(14;16), t(14;20), del17p13, or gain of 1q by FISH; del 13 or aneuploidy by karyotyping; and ISS stage 3; patients without these features and with standard risk attributes were classified as SRM, while any patients with missing attribute information were classified as having undetermined risk myeloma (URM). In the study population, there were 135 SRM, 100 HRM, and 104 URM patients. Median age of the entire cohort was 60 years (76-34). The patients underwent hematopoietic cell mobilization and collection with filgrastim ± plerixafor and were conditioned with high-dose Melphalan (140-200 mg/m2). When possible, patients with SRM underwent single HCT (S-HCT) and those with HRM, tandem HCT (T-HCT) based on risk classification, response to prior therapy, insurance mandate and patient/physician preference. In those undergoing T-HCT, the median time to second HCT was 141 days. Evaluating the entire study population, and comparing patients who underwent a T-HCT (median follow up 82 mo.) vs. a S-HCT (85 mo.), there was no significant difference in OS (adjusted HR 1.1, 95% CI: 0.7-1.8; Cox proportional hazard model, adjusted for age, gender and risk group) (Figure 1) and PFS (HR 0.9, 95% CI: 0.6-1.2) between these two treatment groups. Of the 135 SRM patients, 20 underwent T-HCT; there was no significant difference in OS (HR = 1.2, 95% CI 0.5-2.9) and PFS (HR = 0.9, 95% CI = 0.5-1.7) in these patients compared to those undergoing S-SCT. Of the 100 HRM patients, 46 underwent T-HCT (P &lt;0.01 c/w SRM & URM for T-HCT assignment). Again, there was no significant difference observed in OS (HR = 1.3, 95% CI = 0.7 - 2.5) (Figure 2) and PFS (HR = 1.0, 95% CI = 0.6 - 1.8) in the T-HCT recipients as compared to S-SCT amongst the HRM patients. Similar outcomes were observed in the URM patients. There were no differences observed between S-HCT and T-HCT outcomes in patients with deletion of chromosome 17p or in those with ISS stage 3 disease in OS (HR = 1.7, 95% CI = 0.8 - 3.8) and PFS (HR = 1.0, 95% CI: 0.5, 1.9). Overall, HRM patients had a trend for worse, albeit not significantly different, OS (HR 1.4, 95% CI: 0.9-2.2), as well as PFS (HR 1.1, 95% CI 0.7-1.6) compared to SRM; URM demonstrated a similar trend vis a vis SRM. This retrospective review of survival in SRM and HRM transplanted at a single center demonstrates that in the era of induction and maintenance therapy with novel agents, tandem transplantation does not improve OS or PFS in either SRM or HRM patients compared to a single transplant. Standard of care for newly diagnosed multiple myeloma patients who are transplant eligible should remain induction therapy with novel agents followed by single autologous HCT and maintenance therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals PENGARUH PERUBAHAN STATUS, EMPLOYEE ENGAGEMENT, DAN PEMANFAATAN TEKNOLOGI INFORMASI TERHADAP KUALITAS PELAPORAN KEUANGAN

2017 ◽  
Vol 19 (4) ◽  
pp. 495
Author(s):  
Nani Yuheti Yuniatin ◽  
Noer Azam Achsani ◽  
Hendro Sasongko
Keyword(s):  
Information Technology ◽  
Employee Engagement ◽  
Financial Reporting ◽  
Financial Management ◽  
Test Results ◽  
Financial Reports ◽  
Significant Difference ◽  
Before And After ◽  
The Status

This study aimed to examine the effect of changes in status, employee engagement, and the utilization of information technology on the quality of financial reporting. Analysis of variance (ANOVA) was used to examine changes in the status of Bogor Agricultural University. Moreover we employ a multiple regression analysis to examine the effect of employee engagement and information technology in performance financial of report.  In addition, Ultrecht Work Engagement Scale (UWES) was used to examine the financial human resource mapping. The results of ANOVA test showed that there was no significant difference of the financial management of Bogor Agricultural University before and after the implementation of Public Service Board (BLU). Furthermore, multiple linear regression test results showed that the factors that affect the performance of financial reports are employee engagement and use of information technology. However, it is found that the factor that really affects the performace of financial reports is the use of information technology. Finally, the test results of the mapping showed that employee engagement of human resources staff of Bogor Agricultural University are in medium position indicating that it needs to be maintained and improved.

Nutritional Status of the Children with Acute Lymphoblastic Leukemia at Diagnosis and after Completion of Induction

2021 ◽  
Vol 5 (02) ◽  
pp. 50-56
Author(s):  
Noor-A-Sabah Liza ◽  
S. M. Rezanur Rahman ◽  
Afiqul Islam ◽  
Chowdhury Yakub Jamal ◽  
Mohosina Sultana Setu ◽  
...  
Keyword(s):  
Nutritional Status ◽  
Serum Albumin ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Serum Albumin Level ◽  
Albumin Level ◽  
Anthropometric Measurements ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Nutritional Status Of Children

Background: Adequate nutrition is an important concern in children with leukemia. Malnutrition and weight lost are common and are due to verity of mechanism involving the tumor, the host response to the tumor such as infection and pharmacokinetics of chemotherapeutic drugs. Objective: To evaluate and compare the nutritional status of children with ALL at diagnosis and after completion of induction therapy. Methodology: This prospective observational study included 60 children newly diagnosed as ALL, aged 2-15 years, over a period from April 2012 to September 2012 in the Department of Pediatric Hematology and Oncology, BSMMU. The anthropometric measurements and serum albumin level were taken. Anthropometric indices are calculated by NCHS (WHO-2000) and classified as Z score. Children <-2 SD are considered as underweight (WFA), stunted (HFA) and wasted (WFH). Serum albumin level below 21g/dl is considered as severely malnourished. The Hb values of the children are compared with normal values by age. The children got induction chemotherapy according to MRC-11 protocol. They were in regular follow up and again anthropometric measurements and serum albumin level were taken after completion of induction. Results: Out of 60 children with ALL, 48 (70%) were underweight, 45 (75%) were stunted 36 (60%) were wasted at diagnosis. Incidence of malnutrition among leukemia children after completion of induction were 24 (40%) underweight, 45 (75%) were stunted and 6 (10%) were wasted. The results showed that children in the newly diagnosed stage had a higher prevalence of malnutrition. However no statistically significant difference in the nutritional status was found among newly diagnosed and after completion of induction in term of underweight and stunting but newly diagnosed patients had statistically significant wasting than patients who had completed induction chemotherapy. No patient showed severe malnutrition based on the cut-off point for serum albumin on both stages. All the children (100%) had less than normal range hemoglobin levels. Conclusion: Malnutrition was higher in children with newly diagnosed leukemia. Children had significant differences in the nutritional status in term of wasting at diagnosis than after completion of induction therapy. So, the nutritional status of children with leukemia should be monitor periodically.

ECOG-ACRIN EAA181: Effective quadruplet utilization after treatment evaluation (EQUATE)—a randomized phase 3 trial for newly diagnosed multiple myeloma (NDMM) not intended for early autologous transplantation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS8052-TPS8052
Author(s):  
Shaji Kumar ◽  
Zihan Wei ◽  
Michael A. Thompson ◽  
Bradley Snyder ◽  
Matthias Weiss ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Residual Disease ◽  
Intensive Therapy ◽  
Autologous Transplantation ◽  
Chronic Obstructive ◽  
Newly Diagnosed ◽  
Operating Characteristics ◽  
Obstructive Pulmonary Disease ◽  
Depth Of Response

TPS8052 Background: The monoclonal antibody (MoAb) daratumumab (dara) has been approved for treatment of newly diagnosed Multiple Myeloma (NDMM) in combination with lenalidomide (len) and dexamethasone (DRd) in patients who are not eligible to undergo stem cell transplantation (SCT). Ongoing trials are examining the role of adding bortezomib (Btz) to DRd, but it remains unclear if all patients benefit from a quadruplet regimen. Availability of sensitive assays to detect measurable/minimal residual disease (MRD) in MM and emerging data demonstrating significant prognostic value for attaining MRD negativity, offers an unprecedented opportunity to develop individualized treatment approaches. An important question is to identify who benefits from adding a fourth drug to the MoAb-IMiD triplet, thus individualizing therapy based on depth of response. We hypothesize that prolonged intensive therapy with the addition of Btz for consolidation and maintenance after DRd induction therapy for NDMM will improve survival outcomes with a more pronounced effect when used in MRD positive patients. Methods: Patients with NDMM, R-ISS Stage I or II, who are not eligible to undergo SCT or those willing to defer SCT to first relapse and have not received more than 1 cycle of any NDMM therapy will be enrolled, provided they have measurable disease, adequate organ and marrow function, have received no more than once cycle of therapy for MM and significant peripheral neuropathy or chronic obstructive pulmonary disease. Importantly, a dominant clone should be identified by lymphotrack assay for future MRD monitoring. Once enrolled, induction therapy will be in 28 day cycles consisting of daraSC (1800 mg) weekly for 2 cycles, every other week for cycles 3-6 and then every 4 weeks for 9 cycles, along with len 25 mg days 1-21 of each cycle and dex 40 mg (20 mg for those > 75 years) weekly. At end of 9 cycles (induction), patients will undergo MRD testing by next generation sequencing and will be classified into MRD positive or negative subgroups. Using MRD as an integral biomarker, the trial employs a randomized biomarker-stratified design as proposed by Freidlin et al. to determine efficacy for each MRD subgroup. Patients will be stratified by MRD status and R-ISS stage and randomized to receive 9 cycles of consolidation with DRd, without (control arm) or with (experimental arm) Btz (1.3 mg/m2 weekly for 3 of 4 weeks), followed by DR maintenance until progression The primary endpoint is consolidation OS. Sample size considerations rest on estimates of MRD subgroup prevalence at the end of induction and operating characteristics establishing the treatment effect within the MRD positive subgroup as primary and MRD negative subgroup as key secondary. The total accrual goal is 1450 patients. Clinical trial information: NCT04566328.

Maintenance Therapy With Bortezomib and Dexamethasone for Transplant-ineligible Patients With Multiple Myeloma

2021 ◽  
Vol 1 (2) ◽  
pp. 35-42
Author(s):  
YURIKA NOGUCHI ◽  
NORIYOSHI IRIYAMA ◽  
HIROMICHI TAKAHASHI ◽  
YOSHIHITO UCHINO ◽  
MASARU NAKAGAWA ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Survival Rates ◽  
Patient Characteristics ◽  
Newly Diagnosed ◽  
Estimated Glomerular Filtration Rates ◽  
Overall Survival Rates ◽  
Maintenance Group

Background/Aim: Here, we investigated whether bortezomib as a maintenance therapy affected outcomes in transplant-ineligible patients with multiple myeloma (MM). Patients and Methods: Following induction therapy with bortezomib, maintenance therapy with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) was administered once or twice every 4 weeks until disease progression. The endpoints of this study were time to next treatment and overall survival. Results: Seventy-six newly diagnosed, transplant-ineligible patients were treated with a bortezomib-based regimen; 28 discontinued induction therapy, 27 did not receive maintenance therapy after induction therapy (the non-maintenance group), and 21 did (the maintenance group). In the three groups, the median times to the next required treatment were 3, 14, and 37 months, respectively. The 3-year overall survival rates were 55%, 69%, and 85%, respectively. There were no significant differences in patient characteristics between the non-maintenance and maintenance groups, except for poorer estimated glomerular filtration rates in the maintenance group. Conclusion: Bortezomib maintenance therapy may be a useful option for transplant-ineligible patients with MM.

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