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  • American Society of Hematology  (8)
  • Kim, Jeong-A  (8)
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  • American Society of Hematology  (8)
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  • 1
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 2683-2683
    Abstract: Abstract 2683 Background Secondary central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) includes CNS relapse or CNS involvement with systemic disease progression. Although many publications have provided information regarding the incidence and risk factors for CNS involvement in DLBCL, its incidence reported across those studies varies widely. It might be related with that the majority of data were from retrospective analyses. Furthermore, the role of CNS prophylaxis for DLBCL has been challenged, especially in the era of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). As a result, this rare but fatal clinical problem still remains a therapeutic dilemma in the management of DLBCL. In this study, we prospectively explored the risk factors of CNS involvement and the clinical impact of screening evaluation for CNS involvement. Methods We analyzed the incidence of secondary CNS involvement in pathologically confirmed DLBCL patients enrolled in the Prospective Cohort Study with Risk-adapted Central Nervous System Evaluation in Diffuse Large B-cell Lymphoma (PROCESS study, NCT01202448). Patients should be treated with at least one cycle of R-CHOP, and provide written informed consents. We assessed the risk of CNS involvement based on previously reported risk factors: serum LDH elevation, the number of extranodal involvements, serum albumin, bone marrow invasion, HIV positivity, the involvement of testis, breast, paranasal sinus, bone, retroperitoneal lymph nodes, orbit, and epidural space. If patients had any of these risk factors, they underwent CSF study to screen the CNS involvement at diagnosis. If the results were abnormal, additional studies including brain MRI could be done depending on physicians' decision. CNS prophylaxis was done with intrathecal chemotherapy with methotrexate for patients who had positive findings of screening evaluation or were determined to have a risk of CNS involvement based on physicians' decision. Results 564 patients were enrolled between 2010 and 2012 from 26 institutions belonged to the Consortium for Improving Survival of Lymphoma (CISL). They were prospectively monitored with the median follow-up duration of 10.5 months. The median age was 59.5 years old (range 20–89 years), and approximately a half of patients had Ann Arbor stage III/IV (n = 276, 48.9%) and 193 patients involved two or more than two extranodal sites (34.2%). Based on the International Prognostic Index (IPI) risk, 192 patients belonged to high or high-intermediate risk (34%). Among patients (n = 368) who had at least one of risk factors for CNS involvement, 243 patients underwent CNS evaluation, and the evidence of CNS involvement was found in16 patients including positive cytology (n = 11), and brain parenchyma lesion (n = 5). The other 78 patients showed equivocal results of CSF analysis including the presence of atypical cells (n = 17). Intrathecal prophylaxis was done for 51 patients whereas high dose methotrexate chemotherapy was combined with R-CHOP for patients with brain lesion. During follow-up, 14 cases of additional CNS involvement including brain parenchyma (n = 8), leptomeningeal (n = 5), and ocular invasion (n = 1) were observed. The median time to CNS event in these 14 patients was 7.5 months (range 1.2 – 15.9 months). Thus, 30 cases of secondary CNS involvement were documented in our study population at the time of analysis (5.3%) including 16 cases at diagnosis and 14 cases during follow-up. The univariate analysis for evaluation of risk factors demonstrated serum LDH, the number of extranodal involvements, bone marrow invasion, and the involvement of retroperitoneal lymph nodes, breast, paranasal sinus and orbit were significantly associated with CNS involvement. The high/high-intermediate risk of IPI was also predictive of CNS involvement (P 〈 0.05). However, in the multivariate analysis, bone marrow invasion and the involvement of breast, paranasal sinus and orbit were independently predictive for CNS involvement. Conclusions The incidence of secondary CNS involvement in DLBCL patients treated with R-CHOP was around 5%, and a half of cases had the evidence of CNS involvement at diagnosis. Considering a particular risk of CNS involvement of disease-related factors, risk-adapted active screening against CNS involvement may help to improve treatment outcome of patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 2
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4421-4421
    Abstract: Introduction Although several previous studies addressed the role of radiation in treating localized diffuse large B-cell lymphoma (DLBCL), chemotherapy alone has shown promising efficacy with the emergence of Rituximab. Thus, we evaluated the clinical efficacy outcomes and failure patterns of patients with localized DLBCL according to two different treatment strategies, either 6 or more cycles of R-CHOP chemotherapy alone or 3 or 4 cycles of R-CHOP followed by involved field radiotherapy (IFRT). Methods A prospectively collected database from 21 tertiary centers participating the Consortium for Improving Survival of Lymphoma (CISL), built up for PROCESS study (NCT01202448) for secondary central nervous system involvement in DLBCL, was recruited for current study in addition to the Asan Medical Center (AMC) Lymphoma Registry. CISL database and AMC lymphoma registry consisted of data from patients with newly diagnosed DLBCL between August 2010 and August 2012, and between February 2004 and February 2012, respectively. Inclusion criteria were localized (stage I or II), non-bulky ( 〈 10cm in longest diameter) DLBCL treated with R-CHOP as 1st line chemotherapy, and patients either who received 6 or more cycles of R-CHOP chemotherapy only (R-CHOP alone group) or received 3 or 4 cycles of R-CHOP chemotherapy followed by IFRT (R-CHOP plus RT group). Comparisons of clinicopathologic parameters, clinical outcomes and the patterns of relapse were performed between two groups. The types of relapse were classified as either locoregional or distant, according to whether it involves any separate region from primary sites. Efficacy outcomes included complete response (CR) rate, 2-year overall survival (OS) rate, and 2-year event-free survival (EFS) rate. Results A total of 357 patients (CISL prospective cohort: 161 patients, AMC registry: 196 patients) were eligible for the analyses. Two hundred ninety nine patients (83.5%) received 6 or more cycles of R-CHOP chemotherapy alone, and 58 patients (16.2%) underwent 3 or 4 cycles of R-CHOP followed by IFRT. Median age was 54 years (range, 16-87). During the median follow-up of 24 months (range, 4-116 months), 35 patients (9.8%) experienced relapse, and 22 patients (6.1%) died. Two-year OS and EFS rate was 94.7% and 89.9%, respectively, and 345 out of 357 patients (96.6%) achieved CR. Comparing R-CHOP alone to R-CHOP plus RT group, there was no significant difference in clinicopathologic parameters. R-CHOP alone could achieve significantly higher CR rate of 97.7 % than 91.4% of R-CHOP plus RT group (p = 0.030). Two-year OS and EFS were significantly longer in R-CHOP alone group than R-CHOP plus RT group (96.1 vs 89.9 %, p = 0.029 and 91.7% vs 81.8%, p= 0.028) (Figure 1). Relapse rate was significantly lower in R-CHOP alone group compared with R-CHOP plus RT group than group (7.4% vs 22.4%, p=0.001), and distant relapses were also significantly lower (15.5% vs 2.7%, p 〈 0.001). In addition, even only in relapsed patients, R-CHOP alone group showed lower incidence of distant relapses with marginal statistical significance (36.4% vs 69.2 %, p=0.062) (Table 1). Conclusion In our cohort, R-CHOP alone for six to eight cycles without IFRT could achieve significantly higher 2-year OS and EFS rate as well as CR compared with R-CHOP plus RT group. In addition, the rate of relapse and systemic failure were significantly lower in R-CHOP alone group, which altogether warrant further validation in prospective trial. Table 1. Explorative comparison of overall clinical outcomes and patterns of relapse between two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Total (%) R-CHOP alone group (%) R-CHOP plus RT group (%) P -value Number of patients 357 (100) 299 (83.5) 58 (16.2) Treatment response Complete response 345 (96.6) 292 (97.7) 53 (91.4) 0.030 Overall response 351 (98.3) 294 (98.3) 57 (98.3) 1.000 Rate of relapse 35 (9.8%) 14 (7.4) 11 (22.4) 〈 0.001 Median time to relapse (95% CI) 11 (7-15) 11 (8-14) 10 (5-14) 0.346 Pattern of relapse 〈 0.001 (0.062) Locoregional 14 (4.7) (63.6) 4 (6.9) (30.8) Distant 8 (2.7) (36.4) 9 (15.5) (69.2) Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 3
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1866-1866
    Abstract: Abstract 1866 Background: In multiple myeloma (MM), the association between the response to induction before autologous stem cell transplantation (ASCT) and long-term outcome is less clear but the situation may change with the introduction of novel agents. We therefore assessed the clinical relevance of response of bortezomib induction treatment or post-ASCT response for patients who received bortezomib-combined induction chemotherapy followed by ASCT. Methods: We retrospectively assessed 183 MM patients who received bortezomib-containing induction therapy (BTZ-IT) followed by ASCT in 24 institutions throughout Korea between 2003 and 2010. Records of these patients were reviewed using the Korean Myeloma Registry database (www.myeloma.or.kr). Each institution was requested to reconfirm the data using additional case report forms. Patients who had overt MM based on International Myeloma Working Group diagnostic criteria were selected. Results: One-hundred seventy eight patients were eligible. Their median age was 56 years (range, 28–69 years) and 96 (53.9%) were male. Forty nine (27.5%) received bortezomib as front-line therapy and 129 (72.5%) as second-line treatment. All patients underwent ASCT and 22 (12.4%) were treated with tandem ASCT. Ninety-seven (54.5%) patients were treated with maintenance therapy after ASCT. After BTZ-IT, the response rates in this selected series of patients were 37.6% CR, 12.4% VGPR, 41.0% PR, 7.3% SD and 1.7% PD (Figure 1A, 1B, 1C); the corresponding post-ASCT rates were 69.2% CR, 14.0% VGPR, 11.0% PR, 2.9% SD and 2.9% PD. At a median follow-up of 46.6 months, the 3-year overall survival (OS) and event-free survival (EFS) rates were 70.0% and 31.9%, respectively. Multivariate analysis showed that factors independently predictive of OS and EFS included achievement of BTZ-IT response °Ã PR (P=0.025 and P=0.014, respectively) and the treatment with maintenance therapy (P=0.048 and P=0.001, respectively). Post-ASCT CR vs. °Â VGPR was also an independent prognostic factor for OS and EFS (P=0.0001 and P=0.002, respectively). Conclusion: At least PR to BTZ-IT and CR after ASCT were predictive of survival. These findings suggest that patients who responded to BTZ-IT may benefit from ASCT due to an enhanced quality of response. Maintenance therapy can also affect patient outcomes. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 4
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 1790-1790
    Abstract: Abstract 1790 Introduction The addition of rituximab to standard chemotherapy has substantially improved the survival in patients with diffuse large B cell lymphoma (DLBCL). Previous studies in the pre-rituximab era have identified the worse outcomes in primary extranodal DLBCL compared with nodal DLBCL. However, there have been reported conflicting datas about outcomes of primary extranodal DLBCL compared with nodal DLBCL in the rituximab era. Primary breast DLBCL is one of the extremely rare extranodal lymphoma. As in other primary extranodal lymphoma, few clinical studies have been reported for investigating the efficacy of rituximab in patients with primary breast DLBCL. For clarifying this, a large randomized trial comparing survival in patients with primary breast DLBCL is required. However, the rarity of primary breast DLBCL makes large trial virtually difficult in single center or study group. Additionally, retrospective studies for evaluating the role of rituximab in primary breast DLBCL had bias according to the difference of treatment period between CHOP and R-CHOP era. Thus, to investigate the impact of rituximab in primary breast DLBCL, we performed a matched pair analysis following strict matching criteria in patients with primary breast and nodal DLBCL treated with R-CHOP. Materials and methods Primary breast DLBCL patients treated with R-CHOP was identified from 11 hospitals in Korea between May 2004 and August 2009. The eligibility criteria included: (1) histologically confirmed DLBCL, (2) Ann Arbor stage I or II of primary breast DLBCL, defined as isolated breast involvement with or without nodal disease, (3) received front-line treatment with R-CHOP. Each primary breast DLBCL patient was matched to three nodal DLBCL patients treated with R-CHOP during the same period from the data registry of Korean Lymphoma Working Party. The patients were matched for 5 known prognostic factors: age ( 〈 60 vs. ≥60), Ann Arbor stage (I vs. II), Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0-1 vs. 2–3), serum LDH level (normal vs. elevated), and B symptom (absent vs. present). All factors should be matched between the four matched patients. Results Twenty-five patients with primary breast DLBCL were identified. The median age at diagnosis was 56 (range, 21–79) years and all patients were female. The Ann Arbor stage was I in 13 patients (52%) and II in 12 patients (48%). ECOG PS was 0 or 1 in 23 patients (92%), B symptom was present in 1 patient (4%), and serum LDH level was elevated in 9 patients (36%). Thus, stage-modified international prognostic index (IPI) was 0 or 1 in 20 patients (80%). Eight patients (32%) were received 3 or 4 cycles of R-CHOP followed by involved field radiotherapy and 17 patients (68%) were treated with 6 to 8 cycles of R-CHOP. After matching process, stage-modified IPI, treatment strategy, radiation dose, and follow-up duration as well as 5 matching factors were not significantly different between primary breast and nodal DLBCL groups. With a median follow-up of 34.3 (range, 4.4–76.2) months, 3-year progression-free survival (PFS; 70.0% [59.9-80.1] vs. 85.2% [79.9-90.5] , p=0.145) and overall survival (OS; 82.2% [72.6-92.8] vs. 90.0% [86.0-94.0] , p=0.528) was not statistically different between primary breast and nodal DLBCL groups. In multivariate analysis, 2 or 3 risk factors of stage-modified IPI were independent prognostic factor for worse PFS (hazard ratio [HR], 3.18; 95% CI, 1.22–8.30) and OS (HR, 4.88; 95% CI, 1.55–15.33). Comparing 3-year cumulative incidence of progression between primary breast and nodal DLBCL, extranodal progression in the breast or central nervous system (CNS) was significantly higher in the primary breast DLBCL than nodal DLBCL (23.6 ± 9.3% vs. 1.4 ± 1.3%, p 〈 0.001, respectively). Conclusions In the post rituximab era, the survival outcomes of primary breast DLBCL were not significantly inferior to those of nodal DLBCL. These results suggest adding rituximab improve survival in primary breast DLBCL as in nodal DLBCL, so that the results provide evidence to add rituximab in this rare extranodal DLBCL. However, even including rituximab, extranodal progression in the breast or CNS was observed still high. Thus, further larger studies of international collaboration to confirm these results are warranted. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 5
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 5024-5024
    Abstract: Abstract 5024 Introduction The non-Hodgkin's lymphoma (NHL) with breast involvement is an extremely rare extranodal presentation. The aim of this study is to analyze the clinical features and treatment outcomes of NHL with breast involvement, and to investigate whether the arbitrary classification between primary breast lymphoma (PBL) and secondary breast lymphoma (SBL) has any clinical relevance. Patients and Methods We retrospectively analyzed 98 patients newly diagnosed as NHL with breast involvement from 16 hospitals in Korea between January 1994 and June 2009. The eligibility criteria included: (1) histological confirmation by pathologist should be made, (2) documentation of one or both breasts involvement by histology or imaging modalities was needed. The PBL was defined as disease localized to one or both breasts ± regional lymph nodes (ipsilateral axillary, supraclavicular and internal mammary lymph nodes), and SBL defined as disease with systemic lymph nodes and/or other extranodal organ involvement as well as one or both breasts involvement. Mediastinal and cervical lymph nodes were not regarded as regional lymph nodes. Recurrent lymphomas in the breast following prior treatment were not included in this analysis. Results The median age at diagnosis was 45 (range, 17-83) years, and median follow-up duration was 39.2 (range, 0.5-186.0) months. The two most common histologic subtypes included were diffuse large B-cell (68 patients, 69.4%) and mucosa-associated lymphoid tissue (8 patients, 8.2%) histology. Other 7 histologic subtypes were identified. Among 98 patients, 89 (91%) were treated at least 1 cycles of systemic chemotherapy, 82 (84%) treated with anthracycline-based regimens, 44 (44.9%) treated with combination of chemotherapy and rituximab. Any surgery or any radiotherapy to the breasts was performed in 27 (27.6%) patients, respectively. According to the definition, PBL and SBL group were 58 (59.2%) and 40 (41.8%) patients, respectively. The estimated 5-year progression-free survival (PFS) and overall survival (OS) was 51.2% ± 6.8 and 61.3% ± 6.0, respectively. Overall response rate (ORR) of 93 patients who were evaluable was 91.4% (CR, 76.3%; PR, 15.1%). Compared the baseline characteristics of PBL with those of SBL, PBL group showed more favorable clinical factors as 0 or 1 of Eastern Cooperative Oncology Group performance status (p 〈 0.001), normal LDH level (p=0.003), absence of B symptom (p=0.001) and low or low-intermediate international prognostic index (p 〈 0.001). 14 (24%) of PBL group were treated with abbreviated course (£4 cycles) of systemic chemotherapy and local therapy, 11 (28%) of SBL group were treated 4 or less than 4 cycles of systemic chemotherapy because of mainly disease progression or early death. ORR was significantly higher in PBL group (96.6% vs 72.5%, p=0.005), and estimated 5-year PFS (63.6% ± 8.7 vs 35.2% ± 8.9, p 〈 0.001) and OS (71.8% ± 7.2 vs 45.3% ± 9.9, p=0.004) was also significantly longer in PBL group compared with SBL group. Eight (8.2%) patients had central nervous system (CNS) relapse or progression in the course of disease, and PBL group had a significantly higher rates of CNS relapse or progression compared with SBL group (6 [10.3%] vs 2 [5%] , p=0.046). In multivariate analysis for PFS, 4 or less than 4 cycles of systemic chemotherapy regardless of any local treatments (hazard ratio [HR], 5.14; 95% confidence interval [CI] , 2.18-12.12) and more than 2 of extranodal organ involvement (HR, 10.64; 95% CI, 4.75-23.83) were independent prognostic factors for shorter PFS. And, for OS, 4 or less than 4 cycles of systemic chemotherapy regardless of any local treatments (HR, 4.03; 95% CI, 1.90-8.54) was the only independent prognostic factor for shorter OS. Conclusion Although criteria for PBL and SBL, we traditionally used, did not consider tumor biology and an arbitrary definition, we confirmed that the patients with NHL involved breasts could be classified into two different groups; traditional PBL and SBL according to the clinical characteristics, treatment outcomes and patterns of failure in this analysis. Continuation ( 〉 4 cycles) of active systemic chemotherapy was the only prognostic factor for OS, regardless of any local treatment. Thus, standard systemic chemotherapy should be the mainstay of treatment for NHL involved breasts. And, newer treatment strategy adapted on the poor prognosis should also be warranted. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 6
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 3201-3201
    Abstract: Older MM patients continue to have poor outcomes. Lenalidomide (L) and low dose dexamethasone (D) was found to result in better overall survival than L and high dose D in ND MM (Rajkumar et al. Lancet Oncol 2010). In an attempt to decrease toxicity from therapy in this vulnerable patient population, we have initiated two phase II clinical trials evaluating a response adapted therapy using single agent L with sequential addition of corticosteroids. The trials had similar design and were conducted in one site in the United States (US) and multiple sites in South Korea (SK). Methods Eligible patients had symptomatic standard risk MM (b2microglobulin (b2m)≤5.5, absence of t(4;14), t(14;16), 17p deletion, aneuploidy or 13q by metaphase cytogenetics) and were not eligible or not willing to undergo high-dose melphalan. Patients received L on D1-21 every 28 days for 2 cycles based on renal function. If patients had a minimal response (MR) or better (25% reduction in serum M spike) after 2 cycles, they continued on single agent L until progressive disease. If patients had stable disease (SD) after 2 cycles, prednisone 100 mg PO D1-5 (P) was added to their L. In the event of progressive disease on single agent L or on LP, therapy was changed to L (at the tolerated dose) with dexamethasone 40 mg PO weekly (D). Thromboprophylaxis was with aspirin, warfarin or low molecular weight heparin. Responses were per IMWG and the primary end point was the 1 year progression free survival (PFS)of LD. Results Between 2/2010 and 6/2013, 61 patients were enrolled (34 in SK and 27 in the US). The median age was 73 (range 48-85) and 58% were males. Compared to US, patients in SK had a younger age, lower weight and body surface area and a higher proportion of ISS 2. There were no differences in baseline performance status, hematologic parameters, creatinine clearance or baseline b2m. The overall response rate (≥PR) to single agent L was 48% (59% & 38% for US and SK) and the clinical benefit rate (≥MR) 64% (74% & 56% for the US and SK respectively). After a median follow up of 13.2 months, P was added for 16 patients (26%) and 7 (44%) had ≥PR. D was added for 14 patients (23%) and 10 patients (71%) had ≥PR. The 1 year dexamethasone free survival was 75% (84% & 67% in the US and SK respectively). To date, 3 patients progressed after the addition of D and the 1 year LD PFS was 90% (95% CI 78-96%). There were no statistical differences in grade 3/4 hematologic adverse events (table). Lenalidomide dose reduction was more frequent in the US (59% vs. 26%) however discontinuation from therapy for causes other than progressive disease or death was more frequent in SK (41% vs. 18%). Conclusion In This elderly patient population, response adapted (sequential) therapy results in outcomes comparable to LD in younger patients with MM with 78% of patients not requiring the addition of D. Social and ethnic causes of differential tolerance to therapy should be studied further. Disclosures: Baz: Celgene: Research Funding; Millenium: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding. Off Label Use: lenalidomide in newly diagnosed myeloma. Alsina:Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Shain:Onyx: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity’s Board of Directors or advisory committees. Kwak:celgene: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 7
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2044-2044
    Abstract: Abstract 2044 Background: Induction treatment followed by autologous stem cell transplantation (ASCT) is the standard therapy for the newly diagnosed younger patients with multiple myeloma (MM). Although new drugs such as lenalidomide or bortezomib have been shown the promising results as induction treatment, many different type of induction treatment regimens still have been used. We evaluate the efficacy and safety of the short course of high dose dexamethasone (HD dexa) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods: 107 newly diagnosed patients with MM from 21 institutions received 2nd cycles of HD dexa followed by PAD or VAD chemotherapy according to the response to the initial high dose dexamethasone. The primary endpoint was complete response (CR) + near CR rate after ASCT. Among 107 patents enrolled this study from November 2009, 25 patients (23%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results: One hundred seven patients (58 male, 49 female) were enrolled (median age; 56). 26 (24%) light chain disease were included. 31 (29%) patients were D-S stage II and 67 (63%) were stage III. According to the ISS, 23 (22%) patients had stage I, 51 (48%) had stage II and 33 (31%) had stage III. 26 (24%) patients had abnormal cytogenetics. There were 31% del13, 7% del17, 19% t(4;14), 15% t(14;16) and 28% t(11;14) in FISH analysis. Among the 82 evaluable patients, CR + PR rate was 48% (39/82) after 2nd cycles of HD dexa therapy. 39 patients (48%) received subsequent VAD chemotherapy and 43 patients (52%) received PAD chemotherapy. Among the 64 patients finished VAD or PAD chemotherapy, CR + PR rate was 83% (79%, 26/33 in VAD group vs. 87%, 27/31 in PAD group). 56 patients were finished ASCT until now. CR + near CR rate after ASCT were 61% (58% in VAD group vs 63% in PAD group). Mortality rate of this trial was 13% (11/82). The cause of death was disease progression (n=3), bleeding (n=1) and infections (n=7). Among 82 patients in whom VAD or PAD chemotherapy was actually performed, 1 year overall survival (OS) rate was 84.7%. 1 year survival rate was 93.8% versus 77.2% (P=0.049) with VAD versus PAD (median follow-up; 9.1 months). Conclusion: Risk adapted approach using initial steroid response showed good response results after ASCT compared with previous trial (CR + near CR rate of IFM 2005-01trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who had poor response to HD dexa also showed similar good response rate after ASCT compared with the patients who had good response to HD dexa treatment in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 8
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3106-3106
    Abstract: Abstract 3106 Background: Induction therapy followed by ASCT is the standard therapy for the newly diagnosed younger patients with MM. Recently, new drugs such as lenalidomide or bortezomib have shown the promising results as an induction treatment. However, these drugs are not available in many countries as a front line treatment and many different type of induction treatment regimens including old regimens are used. We evaluate the efficacy and safety of the brief course of high dose dexamethasone (HD) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods: One hundred fifty five newly diagnosed patients with MM from 23 institutions received 2 cycles of HD followed by PAD or VAD chemotherapy according to the response to the HD. PAD 4 cycles were given to nonresponsders and VAD 2 cycles were given to who achieved more than PR to HD. The primary endpoint was CR + nCR rate after ASCT. Among 155 patents enrolled this study from November 2009, 29 patients (19%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results: One hundred fifty five patients (88 male, 69 female) were enrolled (median age; 57). 34 (22%) patients had ISS stage I, 64 (41%) stage II and 55 (35%) stage III. Thirty six (26%) patients had abnormal cytogenetics. In FISH analysis, there were 25% del13, 9% del17, 21% t (4; 14), 13% t (14; 16) and 26% t (11; 14). Among the 115 evaluable patients, CR + PR rate was 53% (61/115) after 2 cycles of HD. 61 patients (53%) received subsequent VAD chemotherapy and 54 patients (47%) received PAD chemotherapy. Among the evaluable patients, CR + PR rate after induction therapy was 83% (79%, 48/61 in VAD group vs. 89%, 48/54 in PAD group). 95 patients finished ASCT. CR + nCR rate after ASCT were 74% (74% in VAD group vs 73% in PAD group). Mortality rate of this trial was 15% (17/115). The cause of death was disease progression (n=5), bleeding (n=1) and infections (n=11). Among 115 patients in whom VAD or PAD chemotherapy was actually performed, 1 year OS was 88.1%. (VAD arm 90.7% versus PAD arm 86.1% (P=0.105): median follow-up; 16.6 months). Conclusion: Risk adapted approach using initial HD response showed good response results after ASCT compared with previous trial (CR + nCR rate of IFM 2005-01 trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who showed poor response to HD also showed similar good response rate after ASCT compared with the patients who had good response to HD in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Our data shows that almost half of the patients who responded to HD can be saved of novel agents during induction treatment, and PAD can successfully rescue the other half who are not sensitive to HD. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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