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  • 1
    Online Resource
    Online Resource
    Elsevier BV ; 1986
    In:  Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment Vol. 244, No. 3 ( 1986-4), p. 455-476
    In: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Elsevier BV, Vol. 244, No. 3 ( 1986-4), p. 455-476
    Type of Medium: Online Resource
    ISSN: 0168-9002
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1986
    detail.hit.zdb_id: 1466532-3
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  • 2
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 2091-2091
    Abstract: Introduction: Bendamustine is a purine analog/alkylator hybrid agent with a unique mechanism of action, which has shown good clinical efficacy and acceptable tolerability in various hematological malignancies, including Hodgkin’s disease, non-Hodgkin’s lymphoma, and multiple myeloma. Patients and Methods: The efficacy and safety of bendamustine and chlorambucil have been compared in a randomized, open-label, multicenter, Phase III trial in patients with previously untreated advanced (Binet stage B/C) B cell chronic lymphocytic leukemia: an updated analysis from this trial is presented here. Patients were randomized to receive bendamustine (100 mg/m2 on days 1 + 2) or chlorambucil (0.8 mg/kg on days 1 and 15) for up to 6 treatment cycles. The median cumulative dose per patient was 1820 mg and 517 mg for bendamustine and chlorambucil, respectively. The primary endpoints were overall remission rate (ORR), which was defined as complete response, nodular partial response or partial response, and progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. The response to treatment was evaluated by a blinded Independent Response Assessment Committee. Results: A total of 319 patients were randomized (162 bendamustine, 157 chlorambucil), of whom all were included in the efficacy analysis and 312 were evaluable for safety. The mean (± SD) number of treatment cycles was 4.8 ± 1.7 in the bendamustine group and 4.6 ± 1.7 in the chlorambucil group; the median duration of follow-up was 29.2 months (29.8 bendamustine, 27.8 chlorambucil). The ORR was significantly higher with bendamustine than with chlorambucil (67% versus 30%, P & lt;0.0001). The median PFS was 21.5 months with bendamustine and 8.3 months with chlorambucil (P & lt;0.0001). No difference in OS was seen between groups. Most doses were given on schedule. The mean overall relative dose intensity was 86% and 96% in the bendamustine and chlorambucil treatment groups, respectively. At least 1 grade 3/4 neutropenia occurred in 43% of bendamustine-treated patients and 21% of those receiving chlorambucil. Grade 3/4 infections were documented in 7% of bendamustine-treated patients and 4% of chlorambucil-treated patients. Conclusion: This study has shown that bendamustine offers significantly greater efficacy than chlorambucil, with manageable toxicity, and should be considered as first-line chemotherapy for patients with advanced B-CLL.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 2971-2971
    Abstract: It is often questionable as to whether or not therapeutic benefit documented in prospective studies reflects that which is observed in routine use. Four prospective studies have explored the efficacy of alemtuzumab in heavily pretreated B-CLL patients, reporting response rates (RR) between 33% to 55%, and median survival between 13–28 months. Here, we report clinical outcomes after therapy with alemtuzumab of 106 consecutive, unselected B-CLL patients treated in 25 centers in Austria. Seventy-two patients were male and 34 female, the median age was 66 years (range, 46–88 years). The majority of patients had advanced stage disease, with 58% having Rai stage IV disease. The patients had received a median of 3 prior therapies (range, 1–11). Alemtuzumab was administered according to guidelines, but in the majority of cases, dosing was individualized, according to tolerability, side effects, and economic considerations. Thus, the median duration of therapy was 7 weeks (range, 2–24 weeks), and median dose was only 390 mg (range, 11–1333 mg). Therapeutic response was determined, strictly adhering to the NCI criteria (duration of complete response [CR]/partial response [PR] /stable disease [SD] ≥ 2 months; adequate radiologic studies of all non-palpable manifestation; marrow for CR). CR, PR, and SD were achieved in 5%, 17%, and 34% of patients (RR 22%). Progressive disease occurred in 34%, and responses were not evaluable in 9%, due to early death. In the 59 patients with overall CR/PR/SD, peripheral blood responses were as follows: 63% CR, 25% PR, and 12% SD. Survival times were encouraging and comparable with other studies. The median survival for all patients was 19 months; 15 months for fludarabine-refractory patients (n = 67) and 31 months for fludarabine-sensitive patients (n = 24; P = 0.04). Survival was dependent on response (P = 0.0001), the number of previous therapy lines (0–3 vs & gt;3; P = 0.0001), and the presence of bulky disease (P = 0.005). Route of administration (IV: 49%; IV to SC 38%; upfront SC 13%) did not influence outcome. Toxicities were within the expected range, with grade 3/4 infections in 37% of patients; grade 4 neutropenia and thrombocytopenia in 25% and 23% of patients, CMV reactivation in 14% (CMV disease in 3%) of patients, and early death ( & lt;2 months after last dose) in 12% of patients. We conclude that in the routine clinical setting, alemtuzumab is a safe and effective treatment with profound prolongation of survival in pretreated B-CLL patients. This retrospective study is an important contribution to continuous, nationwide quality control.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: British Journal of Haematology, Wiley, Vol. 159, No. 1 ( 2012-10), p. 67-77
    Abstract: The efficacy of bendamustine versus chlorambucil in a phase III trial of previously untreated patients with B inet stage B/C chronic lymphocytic leukaemia ( CLL ) was re‐evaluated after a median observation time of 54 months in M ay 2010. Overall survival ( OS ) was analysed for the first time. At follow‐up, investigator‐assessed complete response ( CR ) rate (21·0% vs 10·8%), median progression‐free survival (21·2 vs 8·8 months; P  〈   0·0001; hazard ratio 2·83) and time to next treatment (31·7 vs 10·1 months; P  〈   0·0001) were improved for bendamustine over chlorambucil. OS was not different between groups for all patients or those ≤65 years, 〉 65 years, responders and non‐responders. However, patients with objective response or a CR experienced a significantly longer OS than non‐responders or those without a CR . Significantly more patients on chlorambucil progressed to second/further lines of treatment compared with those on bendamustine (78·3% vs 63·6%; P  =   0·004). The benefits of bendamustine over chlorambucil were achieved without reducing quality of life. In conclusion, bendamustine is significantly more effective than chlorambucil in previously untreated CLL patients, with the achievement of a CR or objective response appearing to prolong OS . Bendamustine should be considered as a preferred first‐line option over chlorambucil for CLL patients ineligible for fludarabine, cyclophosphamide and rituximab.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2012
    detail.hit.zdb_id: 1475751-5
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  • 5
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2367-2367
    Abstract: Abstract 2367 Poster Board II-344 Introduction: Bendamustine is a purine analog/alkylator hybrid agent with a unique mechanism of action, which has shown good clinical efficacy and acceptable tolerability in various hematological malignancies. Chronic lymphocytic leukemia (CLL) is a disease of the elderly, and presents with a variety of clinical characteristics which influence the prognosis. We analyzed tolerability and efficacy of bendamustine (BEN) in comparison to chlorambucil (CLB) in clinical risk groups defined by age and specific indicators of disease activity. Patients and Methods: The efficacy and safety of BEN and CLB have been compared in a randomized, open-label, multicenter, phase III trial in patients with previously untreated advanced (Binet stage B/C) CLL. Patients were randomized to receive BEN (100 mg/m2 on days 1 + 2) or CLB (0.8 mg/kg on days 1 and 15) for up to 6 treatment cycles. The primary endpoints were overall remission rate (ORR), which was defined as complete or partial response, and progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. The response to treatment was evaluated by a blinded Independent Response Assessment Committee. Results: A total of 319 patients were randomized (162 bendamustine, 157 chlorambucil), of whom all were included in the efficacy analysis, while 312 were evaluable for safety. Median age was 64 years (35 to 78). The median number of treatment cycles was 6 in both study arms, regardless of an age above or below 65 years. The median observation time was 35 months. ORR was significantly higher with BEN than with CLB (68% versus 31%, P 〈 0.0001). The median PFS was 21.6 months with BEN and 8.3 months with CLB (P 〈 0.0001). So far, there is no difference in OS (median not reached with BEN versus 65.4 months with CLB; p = 0.16). No significant difference in the remission rates became apparent when comparing patients below and above the age of 65 years (ORR 71.6 % versus 63.5 % with BEN, p 〉 0.3; and 28.4 % versus 32.5 % with CLB, p 〉 0.6). PFS was not influenced by age above 65 years, stage of disease (Binet stage B versus C), or elevated LDH. However, patients without B symptoms had a longer median PFS with BEN than those patients with B symptoms (30.4 months versus 17.7 months; p 〈 0.0001), whereas median PFS was not affected by the presence of B symptoms in patients with CLB (8.9 months in both patient groups). Conclusion: This study has shown that bendamustine offers significantly greater efficacy than chlorambucil in the elderly and across clinically defined major risk groups, even in the presence of B symptoms. BEN should be considered as first-line chemotherapy for patients with advanced CLL. Disclosures: Knauf: mundipharma: Consultancy, Honoraria; cephalon: Consultancy, Honoraria. Klein:mundipharma: Consultancy, Honoraria. Merkle:mundipharma: Consultancy, Honoraria. Montillo:mundipharma Italy: Consultancy, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    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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  • 6
    In: British Journal of Haematology, Wiley, Vol. 80, No. 2 ( 1992-02), p. 160-165
    Type of Medium: Online Resource
    ISSN: 0007-1048
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 1992
    detail.hit.zdb_id: 1475751-5
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  • 7
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2449-2449
    Abstract: Abstract 2449 Introduction: Bendamustine (BEN), either alone or in combination with Rituximab, is increasingly used in the treatment of chronic lymphocytic leukemia (CLL) and various types of low grade Non Hodgkin's Lymphoma (NHL). The approval to treat CLL with BEN is based on a prospectively randomized trial (Knauf et al., J Clin Oncol. 2009; 27: 4378–4384) comparing single drug BEN with chlorambucil (CLB). Here, we report on follow-up data of this pivotal trial with specific reference to survival times, time to next treatment, and efficacy of second line regimens. Since CLL is a disease of the elderly and potentially co-morbid patients, we also analyzed quality of life (QoL) parameters in relation to the treatment with both BEN and CLB. Patients and Methods: The efficacy and safety of BEN and CLB have been compared in a randomized, open-label, multicenter, phase III trial in patients with previously untreated advanced (Binet stage B/C) CLL. Patients were randomized to receive either BEN (100 mg/m2 on days 1 + 2) or CLB (0.8 mg/kg on days 1 and 15) for up to 6 treatment cycles. The primary endpoints were overall response rate (ORR), which was defined as complete (CR) or partial response (PR), and progression-free survival (PFS). Secondary endpoints included overall survival (OS), and QoL. The latter was analyzed by using both the EORTC questionnaires QLQ C30 and QLQ-CLL25. We also looked at time to next treatment and efficacy of second line regimens. The response to treatment was evaluated by a blinded Independent Response Assessment Committee. Results: A total of 319 patients were randomized (162 BEN and 157 CLB), all of whom were included in the efficacy analysis, while 308 patients were evaluable for QoL analysis (158 BEN and 150 CLB). Median age was 64 years (range 35 to 78). The mean number of treatment cycles was 5 in both study arms, regardless of an age above or below 65 years. The median observation time was 54 months. ORR was significantly higher with BEN than with CLB (68% versus 31%, P 〈 0.0001). A CR was achieved in 31% of pts with BEN and in 2% of pts with CLB (P 〈 0.0001). In the intent to treat (ITT) population, the median PFS was 21.2 months with BEN and 8.8 months with CLB (P 〈 0.0001). Sixty-three patients in the BEN treated group and 35 in the CLB treated group had not received any second line therapy (P 〈 0.001) at the time of this analysis. The median time to next treatment in the ITT population was 31.5 months with BEN and 10.1 months with CLB (P 〈 0.0001). ORR after second line therapy of any type was 35.4% in the BEN first line arm and 45.9% in the CLB first line arm (P=0.131). So far, there is no difference in OS (P = 0.24; hazard ratio = 1.3 in favour of BEN) in the ITT population. However, patients achieving a CR (almost exclusively after BEN) experienced a longer OS than pts not in CR (median not reached versus 76.2 months; P=0.002). Also, pts with any response (CR + PR) either after BEN or CLB had a longer OS than the non-responders (median not reached versus 68.3 months; P 〈 0.0001). Base line scores regarding QoL parameters showed no difference between the groups. After completion of study treatment (mean 5 cycles administered), no differences became evident with respect to physical, social, emotional, and cognitive functioning. The self assessment of the global health status also revealed no difference. Conclusion: This study has shown that BEN offers significantly greater response rates, PFS, and a much longer time to next treatment than CLB. OS is prolonged significantly in all responders and especially in those patients who achieve CR after BEN. In comparison to CLB, the additional efficacy of BEN was achieved without compromising QoL. BEN should be considered as a backbone drug in first-line chemotherapy of patients with advanced CLL. Disclosures: Knauf: Mundipharma: Consultancy, Honoraria. Klein: Mundipharma: Honoraria. Merkle: Mundipharma: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 26 ( 2009-09-10), p. 4378-4384
    Abstract: This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced (Binet stage B or C) chronic lymphocytic leukemia (CLL). Patients and Methods Patients (≤ 75 years of age) were randomly assigned to receive bendamustine 100 mg/m 2 /d intravenously on days 1 to 2, or chlorambucil 0.8 mg/kg (Broca's normal weight) orally on days 1 and 15; treatment cycles were repeated every 4 weeks for a maximum of six cycles. The response to treatment was assessed according to National Cancer Institute Working Group criteria, and the final determination of response was made by a blinded independent review committee. Results A total of 319 patients were randomly assigned (162 bendamustine, 157 chlorambucil). Complete or partial responses were achieved in 110 (68%) of 162 bendamustine-treated and 48 (31%) of 157 chlorambucil-treated patients (P 〈 .0001). More patients showed complete responses with bendamustine than with chlorambucil (31% v 2%). Median progression-free survival was 21.6 months with bendamustine and 8.3 months with chlorambucil (P 〈 .0001). Bendamustine was also associated with an improvement in duration of remission, compared with chlorambucil (median, 21.8 v 8.0 months). Hematologic National Cancer Institute Common Toxicity Criteria grade 3 to 4 adverse events were more common with bendamustine than with chlorambucil (occurring in 40% v 19% of patients). Severe infections (grade 3 to 4) occurred in 8% of bendamustine-treated patients and 3% of chlorambucil-treated patients. Conclusion Bendamustine offers significantly greater efficacy than chlorambucil, and a manageable toxicity profile, when used as first-line therapy in patients with advanced CLL.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2009
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 4733-4733
    Abstract: Alemtuzumab is the standard therapy for treatment of patients with relapsed/refractory B-CLL. Significant responses have also been documented in the front-line CLL setting, and as well as in first-line therapy of patients with T-PLL, a population with an exceptionally poor prognosis and few available therapeutic options. Limited data available on the therapeutic benefit of alemtuzumab in other aggressive lymphomas such as B-PLL, which is rare, with a heterogeneous clinical course, and often chemoresistant, as well as CLL with Richter’s transformation, which is also characterized by a poor clinical outcome. Here, we present data on safety and efficacy of alemtuzumab in 6 patients with B-PLL, and 2 cases of B-CLL with Richter’s transformation, both of which developed into DLBCL; one B-CLL case was atypical due to negative CD5 expression (CD19+, CD5−, CD23−). Median age for all 8 patients was 62 years (range, 58–72 years), 5 were male, and all had received a median of 3.5 prior therapies (range, 0–11). Two patients were Rai stage II and III, respectively, and 4 had Rai stage IV disease. At baseline, 3 of the 6 patients with B-PLL had poor performance status, as evidenced by exceptionally high leukocyte counts with clinical signs of hyperleukocytosis and fever of unclear origin. IV alemtuzumab 30 mg was administered according to guidelines (3 times a week, 12 weeks scheduled), but in the majority of cases, dosing was individualized. The median duration of therapy was 4.5 weeks (range, 1–12 weeks), and the median dose was 348 mg (range, 3–793 mg). Therapeutic response was determined according to NCI-WG criteria. In the 2 of 3 patients with poor PS at initiation of therapy an objective response could not be determined due to an early death (septicemia with staphylococcus); 1 patient died prior to achieving a full response due to a suspected apoplectic insult, and another patient died due to progressive disease, shortly after starting alemtuzumab. However, 2 (33%) patients with B-PLL achieved stable disease, lasting 7 months in both cases. Both patients gained a clear clinical benefit from treatment with alemtuzumab as evidenced by CR and PR in peripheral blood, individually, and transfusion independence in both patients. These 2 patients appeared to have favourable disease characteristics, as has been described by other investigators (Leukemia & Lymphoma1999; 33:169), and were diagnosed 9 and 11 years before alemtuzumab, respectively. In the 6 B-PLL patients, overall survival (OS) after start of alemtuzumab therapy was very heterogeneous (0.1; 0.2; 0.3; 1; 27+; 28 months), with a longer OS in the 2 patients with SD. In the 2 patients with B-CLL/Richters’s syndrome (as multifocal DLBCL), PD was observed in one after 2 months on alemtuzumab (survival 15 months). The patient with atypical features was receiving alemtuzumab as an 8th line of therapy and achieved a PR lasting for 13 months (OS 31+ months). In summary, we are adding evidence of therapeutic efficacy of alemtuzumab in a subset of patients with rare, chemotherapy refractory B-lymphoproliferative diseases.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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