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  • 1
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    Induction Therapy with “3+7” Chemotherapy Plus ATRA Followed by Consolidations with Three Courses of Idarubicin Alone and Maintenance Therapy with ATRA in Newly Diagnosed Acute Promyelocytic Leukemia (APL) Has An Excellent Leukemia-Free Survival but Minimal Toxicity in Low and Intermediate Risk Groups.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 2072-2072
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2072-2072
    Abstract: Abstract 2072 Poster Board II-49 Backgrounds Currently, there are many efforts to design risk-adapted strategies in newly diagnosed acute promyelocytic leukemia (APL) by modulating treatment intensity and those seem to be an efficient approach to minimize treatment-related morbidity and mortality (TRM) while maintain the potential in cure for each relapse-risk group. We had postulated that maintaining of Ara-C during induction therapy might have acceptable toxicities yet obtaining good CR in newly diagnosed APL, and idarubicin alone during consolidation periods might have excellent LFS and OS with low relapse rate. Patients and Methods Eighty six patients with newly diagnosed APL were enrolled in the “multicenter AML-2000 trial” after informed consents were obtained during the period of January 2000 to July 2007. For remission induction therapy, patients received oral ATRA (45mg/m2/d, maintained until CR) combined with idarubicin (12mg/m2/d, D1-D3) plus Ara-C (100mg/m2/d, D1-D7). After CR achievement, patients received 3 monthly consolidation courses consisting of idarubicin (12mg/m2/d, D1-D3) alone and maintenance therapy with ATRA (45mg/m2/d, D1-D15, every 2 month) alone had continued for 2 years. Total patients were divided into low-risk, intermediate-risk and high-risk groups according to a predictive model for relapse risk (Sanz score) based on pretreatment WBC and platelet count and the treatment outcomes were compared in the different risk groups. Results The median age of our cohort was 40 years old (range; 6-80) and median follow-up was 27 months (range; 1-90). The distribution of patients in the 3 risk groups was as follows ; 28 (32.6%) patients in low-risk, 40 (46.5%) in intermediate-risk and 18 (20.9%) in high-risk. Overall, CR was achieved in 78 (90.7%) of 86 patients. The CR rate according risk groups was 96.4% in low-risk, 87.5% in intermediate-risk, and 88.9% in high-risk group and there was no significant statistical difference among the different risk groups. During induction therapy, 48 (55.8%) patients experienced grade 3-4 treatment-related toxicity (TRT), mostly fever and infection (38.8% of all patients) and 6 (7.0%) patients died of treatment-related complications. During 3 consolidation courses, 25 (29.1%) of 78 patients experienced grade 3-4 TRT in 1st course, 27 (36.0%) of 75 patients in 2nd course, and 14 (28.0%) of 50 patients in 3rd course. Overall, 3 (3.5%) patients died of treatment-related complications in CR. The incidence of TRT and treatment-related mortality (TRM) during induction or consolidation therapy showed no significant statistical difference among the different risk groups. The relapse occurred in 6 (7.0%) patients; 2 cases in intermediate-risk and 4 cases in high-risk. However, none had relapsed in low risk group, 5 patients of relapsed patients relapsed during consolidation courses and only one patient, however, relapsed during maintenance therapy. The overall survival (OS) and leukemia-free survival (LFS) rate at 7 years in all of patients was 76.7% and 83.5%, respectively. The OS rate at 7 years was 92.9% in low-risk, 78.6% in intermediate-risk and 53.6% in high-risk group (P:0.04) and the LFS rate at 7 years was 96.4%, 83.4% and 62.2% respectively, showing the significant difference between 3 different risk groups (P:0.046). Conclusions This study indicates that our protocol composed of induction therapy with “3+7” chemotherapy plus ATRA followed by consolidations with three courses of idarubicin alone and maintenance therapy with ATRA alone yields a high CR rate and low relapse rate but minimal acceptable toxicities. Despite of adding Ara-C during induction therapy, we did not find much significant toxicities but having good CR rates, and despite of not adding any additional low/intermediate dose chemotherapies(ie, 6MP), we were able to observe significantly high relapse rate in low and intermediate risk group with excellent LFS and OS. Meanwhile, in high-risk group, the relapse rate was significantly higher than other risk groups and most of the relapses occurred in the middle of consolidation courses. This data suggests that our consolidation therapy composed of anthracycline alone may be not enough to minimize risk of relapse in high-risk group in contrast with the low and intermediate-risk groups. More intensive consolidation therapy combined with other effective, but get tolerable chemotherapies or hematopoietic stem cell transplantation in first CR or the combination of arsenic trioxide or others in front-line therapy should be considered in the patients with high-risk of relapse. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.2072.2072
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 2
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    Restrospective Multicenter Study Evaluating Efficacy and Safety of Dasatinib and Nilotinib in Patients with Imatinib-Resistant or –intolerant Chronic Myeloid Leukemia in Chronic Phase: Korean CML Working Party
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 1691-1691
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1691-1691
    Abstract: Abstract 1691 Dasatinib and nilotinib have been founded to be effective and well-tolerated in patients who develop resistance or intolerance to imatinib. Not enough data are currently available to recommend one over the other as the preferred second-line therapy based on efficacy data. Therefore we planned a multicenter retrospective study to analyze the efficacy and safety of dasatinib and nilotinib in patients with imatinib-resistant or –intolerant chronic myeloid leukemia in chronic phase. In this Korean multicenter study, 126 patients imatinib-resistant or –intolerant chronic myeloid leukemia in chronic phase were treated with dasatinib (n=76) or nilotinib (n=50) The purpose of this study was to compare rates of cytogenetic and molecular response rate, event-free survival (EFS), progression-free survival (PFS) and overall survival (OS), and toxicities of nilotinib and dasatinib treatment of imatinib-resistant or –intolerant chronic myeloid leukemia in chronic phase. PFS was defined as the time from the start of treatment to the earliest date of any of following event: loss of complete hematologic response (CHR), loss of major cytogenetic response (MCyR), progression to accelerated phase (AP) or blastic phase (BP), discontinuation due to treatment failure as assessed by the clinician, and death from any cause on therapy. Event was defined by any one of the following: loss of CHR, loss of MCyR, progression to AP or BP, discontinuation due to treatment failure as assessed by the clinician, treatment discontinuation due to toxicity, and death from any cause on therapy. For dasatinib and nilotinib group, median ages (51 years old vs. 53), median durations of CML (23.7 months vs. 19.8 ) before receiving dasatinib or nilotinib and duration of prior imatinib treatment (21.7 months vs 17.7) were comparable. Nilotinib group had a higher proportion of intermediate and high sokal scores at the time of diagnosis than dasatinib group (41.5 vs 29.3% (high), 41.5% vs 32.5%(intermediate), 17.1% vs 37.9(low), p= 0.04). After median follow-up durations of 20.2 months of dasatinib group and 25.3 months of nilotinib group, the rates of major molecular response were 50.0% for dasatinib group and 59.6% for nilotinib group (p=NS) and the rates of MCyR (complete and partial cytogenetic response) were 78.4% for dasatinib group and 74.5% for nilotinib group (p=NS). The estimated EFS at 24 months was 67% and 48% in dasatinib and nilotinib group, respectively. (p 〈 0.05). The estimated PFS at 24 months was 85% and 56% in dasatinib and nilotinib group, respectively. (p 〈 0.05) Overall survival rates were comparable in both treatment groups (24-months OS; dasatinib 91%, nilotinib 94%; p=0.65). Both were generally well tolerated. Hematologic toxicities were more frequent among patients receiving dasatinib. 10 patients (13%) had pleural effusion in dasatinib; 9 events were grade 1 or 2. Elevated liver enzyme were more frequent among patients receiving dasatinib. In conclusion, In this study population, nilotinib and dasatinib showed similar cytogenetic and molecular response rates and survival. Toxicity profiles of two drugs were different and both drugs showed tolerable toxicities. In terms of event-free survival and progression-free survival, dasatinib was superior to nilotinib, but caution is warranted in interpretation because baseline characteristics including hematologic and cytogenetic response at the time of start with dasatinib and nilotinib and sokal scores at the time of diagnosis were different. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.1691.1691
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 3
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    Final Report of “Korean Multicenter AML-2000 Trial”: Intention to Treat Analysis Based on Cytogenetics Risk
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 2975-2975
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 2975-2975
    Abstract: Cytogenetics is still being considered the most powerful single prognostic factor, which is useful to determine the types of post-remission therapy in AML, though various molecular markers are available for predicting the prognosis of AML patients. Most phase III studies have failed to demonstrate a clear advantage of allografting over chemotherapy in terms of overall survival because of significant risk of transplant-related mortality. Optimal post-remission therapies in terms of frequencies (number of treatment) or intensities are not decided yet. In this study, since 2000, we investigated that outcomes of post-remission therapies(high-dose cytarabine (HDAC) vs autologous stem cell transplantation (AutoSCT) vs allogeneic stem cell transplantation from sibling or unrelated donors (AlloSCT)) based on cytogenetic risk (GPG, Good prognosis group; IPG, Intermediate prognosis group; PPG, Poor prognosis group by MRC definition) on the AML patients who achieved complete remission after induction chemotherapy. The aims of this prospective intention to treat analysis was to compare the CR, recovery kinetics, DFS and OS in the different prognostic groups. Three plus seven (idarubicin 12mg/m2, D1–D3; cytarabine 100mg/m2, D1–D7) were given to de novo AML, secondary AML and therapy-related AML. Then, HDAC or AutoSCT was given after intermediate dose (8gm/m2) of cytarabine to the patients with GPG. Three times of post-remission therapy including HDAC, or AutoSCT followed by two times of post-remission therapy were given to IPG or PPG. If HLA-identical sibling was available, then AlloSCT underwent after 1st post-remission therapy. Since January, 2000, 506 patients(18 centers) were enrolled up to December, 2007. Among them, 92.3% was de novo AML, and GPG, IPG and PPG were, 23.1%, 62.1% and 14.8% respectively. Over all complete remission rate after 1st induction was 79.0% and CR rate in GPG, IPG, PPG were 92.0%, 81.0% and 43.9% respectively(P & lt;0.001) in 476 patients who were eligible to this study. In Good Prognosis Group (GPG), survivals were not different between different treatment groups (5 year LFS: HDAC 34.2%, AutoSCT 63.5%, AlloSCT 54.8%, p=0.270; 5 year OS: HDAC 54.5%, AutoSCT 62.5%, AlloSCT 53.3%, p=0.676). However, beneficial effect of AlloSCT in post-remission therapy therapy was observed by multivariate analysis in terms of LFS compared to HDAC (HR of relapse for HDAC 3.198 compared to AlloSCT, p=0.045). Outcomes of HDAC group were inferior in GPG in terms of OS and LFS compared to other studies. This results may be due to low cumulative dose of Ara C, because patients of HDAC group in GPG treated just 1 cycle of IDAC before HDAC therapy. In addition, in our cohort, majority (80%) of GPG have t(8;21), which are known as having inferior survival results, compared to inv(16) group. In Intermediate Prognosis Group (IPG), survivals were not different among different types of treatment (5 year LFS: HDAC 31.1%, AutoSCT 42.4%, AlloSCT 55.0%, p=0.131; 5 year OS: HDAC 39.2%, AutoSCT 42.5%, AlloSCT 46.5%, p=0.491). AlloSCT group showed a trend of being superior to other therapeutic modalities in terms of LFS (p=0.07). AutoSCT group showed a trend of being superior to other therapeutic modalities in OS by multivariate analysis (HR of death for AutoSCT 0.539 compared to AlloSCT, p=0.085). In Poor Prognosis Group (PPG), though data showed slightly beneficial effect of AlloSCT in AML therapy, however, there were no significant statistical differences on OS/LFS in 3 types of consolidation therapy modalities (4 year LFS: HDAC 48.3%, AutoSCT 0%, AlloSCT 39.1%, p=0.379; 4 year OS: HDAC 21.4%, AutoSCT 33.3%, AlloSCT 56.1%, p=0.638). Based on this trial, Allo- or Auto-SCT over HDAC may have beneficial effects in some subgroup with high risk and young age, among the patients with good and intermediate cytogenetic risk. In GPG, “sufficient cumulative dose” of Ara C seems to be necessary to have a good outcome. However, GPG seems to be heterogenous group in terms of biology having poor prognosis when one has additional CG abnormalities on top of t(8;21) or inv(16), which ones need to investigate further. While finding more effective anti-AML molecules/monoclonal Ab’s are necessary, good therapeutic rationales in terms of choosing AlloSCT vs AutoSCT vs HDAC should be established. Same time, identifying for better cellular and molecular prognostic factors over cytogenetics are still relevant for designing “effective therapies, but minimal toxicities”.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.2975.2975
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 4
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    Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 6 ( 2015-08-06), p. 746-756
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 6 ( 2015-08-06), p. 746-756
    Abstract: Nilotinib plus multiagent chemotherapy was feasible and showed a comparable outcome to previous results with imatinib for Ph-pos ALL. The achievement of deep MR with nilotinib at postremission correlated well with the clinical outcomes for Ph-pos ALL.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2015-03-636548
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 5
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    Nilotinib Combined With Multi-Agent Chemotherapy For Adult Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Final Results Of Prospective Multicenter Phase 2 Study
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 55-55
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 55-55
    Abstract: We previously reported the interim analysis on the clinical outcome of nilotinib (Tasigna®, Novartis Pharma, Basel, Switzerland), when combined with multi-agent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) in adults. Herein, we reported the final results of the multicenter prospective phase2 trial of Adult Acute Lymphoblastic Leukemia Working Party, the Korean Society of Hematology. Newly diagnosed Ph+ALL patients aged 18 years old or more were eligible when they had adequate organ function. Diagnosis of Ph+ALL was performed via confirmation of the presence of Ph chromosome by conventional GTL-band technique, and/or positive molecular analysis with nested RT PCR for detection of BCR-ABL fusion transcripts. Written informed consent was obtained from all subjects. All patients received induction treatment consisting of vincristine, daunorubicin, oral or parenteral prednisolone, and nilotinib. After achieving complete remission (CR), subjects received either 5 courses of consolidation followed by 2-year maintenance with nilotinib, or allogeneic hematopoietic cell transplantation (alloHCT) depending on the donor availability, his/her tolerability, and patient’s wish. Nilotinib was administered twice a day with a single dose of 400mg (800mg per day) from day8 of induction until the initiation of conditioning for alloHCT or the end of maintenance therapy. Minimal residual disease (MRD) monitoring was performed at the central lab with quantitative RT-PCR assays for peripheral blood BCR-ABL RNA using LightCycler® Technology in serial; at the time of diagnosis, at hematologic CR(HCR), and every 3 months thereafter. BCR-ABL quantification was expressed relative to the amount of glucose-6-phosphate dehydrogenase (G6PDH) mRNA. The molecular response was defined as complete (MCR, MRD-negative) if the BCR-ABL/G6PDH ratio was less than 1x10-6. Toxicity was graded according to National Cancer Institute Common Toxicity Criteria (version 2.0). Subjects had been followed up for 2 years after alloHCT or during maintenance therapy. Data were frozen up in June, 2013. A total of 91 subjects (male: female = 45: 46) were enrolled onto the study between January 2009 and May 2012. The median age was 47 (range 18-71) years old. Type of BCR breakpoint was minor (e1a2) in 71% of patients. The median BCR-ABL/G6PDH ratio was 6.09 (bone marrow) and 3.28 (peripheral blood) at diagnosis. During induction, all subjects required blood product transfusion, and incidence of nonhematologic adverse events (AE) over grade 3 was 17% (jaundice), 18% (ALT elevation), 13% (lipase elevation), and 2% (pancreatitis). Neither QTc prolongation over 500ms nor significant arrhythmia happened among any subject and any cycle. HCR rate was 90% and median time to HCR was 27 days (range, 13-72); most of failure was due to death in aplasia (n=8). MCR rate at HCR was 55%, Cumulative MCR rate was 84%, and median time to MCR was 1.1 months (range, 0.6-15.8). Most common cause of dropout from study was treatment-related death (n=22; during induction/consolidation vs. after alloHCT = 12 vs. 10), and HREL (n=15). Nilotinib was interrupted 75 times among 64 subjects, reduced 14 times among 12 subjects, and discontinued permanently due to hematologic relapse (HREL, n=14), AE (n=6, over gr3:3), and other cause (n=2). Fifty nine patients underwent alloHCT, 34 with myeloablative and 25 with reduced-intensity conditioning. Incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were 41% and 29%, respectively. With a median follow-up of 20.7 months of surviving subjects, estimated hematologic relapse-free survival (RFS), and overall survival (OS) rate at 2 years were 74% and 70%, respectively. Among subject achieving MCR, 2-year molecular RFS rate was 56%. When events were defined as ‘dropout due to AE, isolated molecular / extramedullary relapse, HREL, and death from any cause’, median event-free survival was 12.5 months. In this prospective study, nilotinib was shown to be effective for adult Ph+ALL, and concurrent administration of nilotinib with cytotoxic drug was well-tolerable, although death in aplasia during induction was the most common cause of failure of achieving HCR. In terms of MRD, potential of nilotinib to achieve and maintain MRD negativity were satisfactory (Clinicaltrials.gov NCT00844298). Disclosures: Off Label Use: Nilotinib for Ph+ALL-sientific and academic purpose.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.55.55
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 6
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    A Multi-Center, Open Label Study Evaluating the Efficacy of Iron Chelation Therapy with Deferasirox in Transfusional Iron Overload Patients with Myelodysplastic Syndromes or Aplastic Anemia Using Quantitative R2 MRI
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 3649-3649
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 3649-3649
    Abstract: Transfusion-related iron overload and its consequences are emerging challenges in chronically transfused patients with myelodysplastic syndromes (MDS) or aplastic anemia (AA). Measurement of liver iron concentration (LIC) is used as a surrogate for total iron burden to guide chelation therapy in transfusion-dependent patients. Although deferasirox (Exjade®, ICL670) is an oral iron chelation agent that is now widely available for the treatment of transfusional hemosiderosis, the clinical data on its specific benefits of iron chelation, including reduction of LIC, in transfusion-related iron overload patients with MDS or AA has been limited. We have prospectively investigated the efficacy of deferasirox for iron chelation by serial measurement of serum ferritin level and LIC, which is measured in vivo using quantitative tissue proton transverse relaxation rates (R2) magnetic resonance imaging (MRI), in transfusional iron overload patients with MDS or AA. Here we report the interim analysis data. A total of 79 patients with de novo MDS (n = 29) or idiopathic AA (n = 50) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. All patients were regularly transfused and received a median of 30 red blood cells (RBC) units in the year prior to the start of the study. Among MDS cases, 3 (10.3%), 20 (69.0%), and 4 cases (13.8%) were categorized as IPSS low-risk, intermediate-1-risk, and intermediate-2-risk group, respectively. In AA cases, 34 (64%) were severe form. Mean value of serum ferritin level in enrolled patients was 4,417 ± 3,378 (4,788 ± 3,996 in MDS, 4,185 ± 2,962 in AA) ng/ml at the time of deferasirox initiation. LIC value was measured using quantitative R2 MRI and FerriScan (Resonance Health, Australia) analysis. Mean value of LIC was 23.9 ± 13.8 (26.1 ± 15.0 in MDS, 22.8 ± 13.2 in AA) mg Fe/g dry weight. Linear regression analysis indicated a close correlation between serum ferritin level and LIC (r=0.55, p 〈 0.001). Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients. If the serum ferritin falls below 500 ng/ml, treatment was withheld. A consistent decrease in the serum ferritin level was demonstrated during the first 6 months in vast majority of patients despite of continued transfusion (209.7 ± 159.9 ng/ml and 324.0 ± 289.4 ng/ml per month in MDS and AA, respectively). Over the study period, patients with MDS or AA received a mean of 3.7 and 2.7 units RBC per month, respectively. After 6 months of medication, a slower decrease in the serum ferritin level was observed in MDS patients. In 30 cases, one-year medication of deferasirox was completed. At the end of study (EOS), the serum ferritin levels were significantly decreased to 3,085 ± 2,150 ng/ml (64.4% of baseline level) and 2,913 ± 2,232 ng/ml (69.6% of baseline level, p 〈 0.01) in MDS and AA, respectively. One-year follow-up R2 MRI could be evaluated in 24 cases, and LIC was significantly decreased to the level of 19.3 ± 13.6 mg Fe/g dry weight (67.4% of baseline value, p=0.01). Decrease in the level of LIC at EOS in MDS (64.3% of baseline) was comparable to that in AA cases (68.5% of baseline). The most common drug-related adverse events (AE) were gastrointestinal disturbances, non-progressive increase in serum creatinine, and skin rash. However, AE were transient and mild-to-moderate in severity. Deferasirox was discontinued in 28 (35.4%) cases because of death (7 in MDS and 6 in AA), patient refusal (11 cases), and decrease in the serum ferritin level below 500ng/ml (4 cases). All death was ascribed to disease-related causes including cytopenia in nine (11.4%) and disease progression in one (1.3%). This study clearly shows that deferasirox is effective in reducing LIC and serum ferritin level in transfusional iron overload patients with MDS or AA, even with ongoing transfusion requirement, and well tolerated. Careful assessment of patient’s transfusion requirement will be important in making dose adjustment according to purpose of iron chelation. Data from extension phase of this clinical trial may expand our knowledge about the beneficial effects of deferasirox on prolonging survival and improving quality of life in these patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.3649.3649
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 7
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    Improved Survival of Patients with Multiple Myeloma and the Impact of Transplantation and Novel Agents: An Analysis of the Korean Multiple Myeloma Working Party (KMMWP).
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 4881-4881
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4881-4881
    Abstract: Abstract 4881 Introduction The Korean Multiple Myeloma Working Party (KMMWP) initiated a nationwide registration of myeloma patients via a web page designated the “Korean Myeloma Registry.” This registry includes demographic features, characteristics of disease, treatment outcomes, and survival status. Herein, we retrospectively reviewed data representing 3,209 Korean myeloma patients. Methods Members of the registry committee of the KMMWP designed the web-based registration site for the “Korean Myeloma Registry (www.myeloma.or.kr).” A total of 3,209 patients were registered from 39 hospitals. Each one of participated hospitals registered their patients who were diagnosed as MM between the years 1999 and 2009. The approximate duration of registration was from May 2005 until March 2009; following collection, the data was downloaded for analysis. Results The median age at diagnosis was 64 years (range, 20 – 93 years) with 84 patients ' 40 years of age; this included three patients 〈 30 years of age (ages 20, 28, and 29 years old). Poor performance status (ECOG grade 2-3), anemia (Hgb 〈 10 g/dL), hypoalbuminemia ( 〈 3.5 g/dL), and elevated serum β2 microglobulin ( 〉 5.5 mg/dL) were more frequently observed in the 〉 65 years of age group than in the groups '65 years of age. Thus, an advanced ISS stage was more common in patients older than 65 years. The most common idiotype of myeloma was IgG (46.0%, 1475/3209), followed by IgA type (18.6%). Non-secretory myeloma accounted for 4.4% of cases, with IgD, IgM, and IgE subtypes being very rare. However, patients ' 40 years of age demonstrated a tendency toward a higher incidence of the IgD type (7.1%, 6/84) and light chain disease (22.6%, 19/84) compared to the other age groups. Other characteristics, including the presence of extramedullary plasmacytoma, demonstrated a similar pattern among the groups. Chromosomal studies of bone marrow aspirates were performed in 1,943 patients with 499 patients (25.7%) demonstrating abnormalities. In 60.9% of patients (1,954/3,209), an objective response to induction treatment included complete response (CR), partial response (PR), and minimal response (MR) (Table 4); 463 patients demonstrated progressive disease (PD) during induction treatment. Response could not be evaluated in 300 patients (9.3%) due to early drop out, including follow-up loss and early death. Eight hundred four patients (25.1%) received SCT. The majority of patients (23.1%, 741 patients) received autologous SCT within one year of diagnosis; designated as “early transplantation.” Autologous SCT was performed in those patients who achieved an objective response following induction treatment. Sixty three patients (2.0%) underwent autologous SCT after relapse; designated as “delayed transplantation.” Five hundred eighty patients received single autologous SCT. Tandem autologous SCT was performed in 134 patients. Allogeneic SCT was performed for 63 patients following autologous SCT. The median OS was 50.13 months (95% confidence interval (CI) of 46.20 – 54.06 months). When OS was compared according to age strata, patients '40 years of age demonstrated a prolonged OS (median OS of 71.13 months) compared with patients 〉 65 years of age (median OS of 36.73 months, P 〈 0.001). When we compared the survival of patients who received novel agents such as bortezomib or thalidomide at any time during the course of their treatments with patients who did not receive novel agents, there was a significant difference of OS between two groups (median OS 42.23 versus 55.50 months, P 〈 0.001). Tandem autologous SCT produced a superior OS when compared with single autologous SCT. Furthermore, patients who underwent delayed SCT demonstrated a longer OS compared with early SCT (P = 0.017). Multivariate analysis found that age 〉 65 years, poor performance status, platelet count 〈 100,000/μL, serum albumin 〈 3.5 g/dL, serum creatinine ≥ 2.0 mg/dL, serum β2 microglobulin ≥ 3.5 mg/dL, the presence of extramedullary plasmacytoma, and the presence of chromosomal abnormalities were all found to be independent prognostic factors for OS. Conclusion In this study, we demonstrate improved survival of patients with multiple myeloma after the introduction of novel agents and autologous stem cell transplantation. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.4881.4881
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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    Efficacy of ICT with Deferasirox in Transfusional Iron Overloaded Patients with MDS or AA.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 3810-3810
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3810-3810
    Abstract: Abstract 3810 Poster Board III-746 PURPOSE Transfusion-related iron overload and its consequences are emerging challenges in chronically transfused patients with myelodysplastic syndromes (MDS) or aplastic anemia (AA). The clinical data on specific benefits of deferasirox in transfusion-related iron overload patients with MDS or AA has been limited. METHODS: We have prospectively investigated the efficacy of deferasirox by serial measurement of s-ferritin level and LIC by R2-MRI in transfusional iron overload patients with MDS or AA. RESULTS: A total of 79 patients with de novo MDS (n = 29) or idiopathic AA (n = 50) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. Mean value of s-ferritin level in enrolled patients was 4,788 ng/ml in MDS and 4,188 ng/ml in AA at the time of deferasirox initiation. Mean value of LIC was 24.4 mg Fe/g dry weight in MDS and 22.4 mg Fe/g dry weight in AA. Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients and was withheld If the s-ferritin falls below 500 ng/ml. Over the study period, patients with MDS or AA received a mean of 3.7 and 2.7 units RBC per month, respectively. After 12 months of medication, s-ferritin level significantly decreased by 1824.0 ng/ml form baseline values, a reduction of 38.1% for patients with MDS (p 〈 0.0001) and significantly decreased by 3559.1 ng/ml (85.0%) for patients with AA (p 〈 0.0001). LIC decreased by 11.2 mg Fe/g dry weight, a reduction of 35.7% for patients with MDS, and significantly decreased by 8.1 mg Fe/g dry weight, a reduction of 27.6% for patients with AA (p=0.0028). The patients with lower transfusional requirements ( 〈 4 units/month) during the study showed significantly more reduction of LIC level than those with higher requirements (≥4 units/month) (35.7% vs. 2.8%; p 〈 0.0001). The most common drug-related adverse events (AE) were gastrointestinal disturbances and non-progressive increase in s-creatinine, however, AE were transient and mild-to-moderate in severity. All death was ascribed to disease-related causes including cytopenia in nine (11.4%) and disease progression in one (1.3%). CONCLUSION: Deferasirox is effective in reducing LIC and s-ferritin level in transfusional iron overload patients with MDS or AA, even with ongoing transfusion requirement, and well tolerated. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.3810.3810
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 9
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    Changes in Osteoblastic Activity in Patient Who Received Bortezomib as Second Line Treatment for Plasma Cell Myeloma: A Prospective Multicenter Study
    Hindawi Limited ; 2014
    In:  BioMed Research International Vol. 2014 ( 2014), p. 1-7
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2014 ( 2014), p. 1-7
    Abstract: We conducted a prospective multicenter study identifying the role of bortezomib in patients with relapsed or refractory plasma cell myeloma (PCM) in bone resorption and formation via bone turnover markers. A total of 104 patients received at least 1 cycle of bortezomib. Most of them had advanced disease ( n = 89 ). Among them, 75 patients completed 4 cycles of treatment. Most of the patients (81.7%) were treated in combination with steroid. After the 4th cycle treatment, 47 of 75 patients achieved CR, nCR, VGPR, and PR (64.4%), while 26 patients achieved less than PR (35.6%). The proportion of patients who achieved ≥ PR increased as patients received more treatment cycles, reaching 90% after the 8th cycle. DKK-1 levels decreased significantly posttreatment. Bone formation markers (bALP and OC) and osteoclast regulator such as sRANKL also decreased significantly. These findings were observed primarily in patients who received steroid and who had a longer disease duration. While sRANKL demonstrated significant reduction posttreatment, osteoprotegerin (OPG) level did not significantly change posttreatment, resulting in a decreased sRANKL/OPG ratio ( P = 0.037 ). In conclusion, our clinical data suggest that treatment with bortezomib and steroid may rearrange the metabolic balance between osteoblast and osteoclast activities in PCM.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2014/245247
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2014
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  • 10
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    The Effect of Bortezomib On Bone Metabolism of Patients with Multiple Myeloma: a Korean Multicenter Prospective Study.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 4871-4871
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4871-4871
    Abstract: Abstract 4871 BACKGROUND Bortezomib is increasingly being employed as an important treatment for relapsed/refractory patients with multiple myeloma (MM) who have received at least one prior therapy. Osteolytic bone disease is a major problem in the management of MM. Myeloma bone disease is a result of excessive osteoclast activation and impaired osteoblast function. METHODS This study aimed to evaluate the effect of bortezomib on bone remodeling in the patients with MM who received one prior therapy. Total 104 patients were enrolled and serum samples were collected from 81 patients at baseline and after 4 cycles of bortezomib treatment, respectively. An enzyme linked immunosorbent assay (ELISA) was used for the detection of the following serum markers; (1) the osteoblastic markers including serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), (2) dickkopf-1 (DKK-1), an osteoblastic inhibitor and (3) a main inducer of osteoclast activity, receptor activator nuclear factor κB ligand (RANKL) and its soluble decoy receptor, osteoprotegerin (OPG). RESULTS There was no correlation between bone disease status and the concentrations of the bone markers; patients with myeloma bone disease at baseline did not have increased values of DKK-1, RANKL and RANKL/OPG ratio as well as decreased levels of OC and BAP when compared with those without osteolytic bone lesions. To our surprise, there was also a strong tendency towards a negative correlation with serum levels of OC (P=.009) and BAP (P=.049) and disease duration (≥ vs. 〈 6 months). Moreover, DKK-1 concentrations were positively associated with disease duration (P=.047). The objective response rate (≥ partial response) after four cycles of therapy was 58%. Bortezomib administration significantly reduced serum DKK-1 (P=.011) and sRANKL/OPG ratio (P=.034) after 4 cycles irrespective of treatment response. OPG levels were significantly different according to the type of previous therapy (stem cell transplantation vs. alkylator-based, P=.029) CONCLUSIONS This study suggests that bortezomib can inhibit the down-regulation of osteoblastic response and bone resorption by reducing circulating levels of DKK-1 and sRANKL/OPG ratio. Serum concentrations of the bone-remodeling markers can be different according to the disease duration rather than the status of bone disease. Bortezomib treatment early after diagnosis may benefit myeloma patients with bone disease considering that the change of bone markers was bound up with disease duration. Disclosures Min: Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Lee:Janssen Korea: Research Funding. Suh:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Yoon:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Kang:Janssen Korea: Research Funding. Choi:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Kwak:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Joo:Janssen Korea: Research Funding. Mun:Janssen Korea: Research Funding. Jo:Janssen Korea: Research Funding. Park:Janssen Korea: Research Funding. Park:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.4871.4871
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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