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  • 1
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 879-879
    Abstract: Abstract 879 As previously reported, dose-escalated first-line therapy with autoSCT as conducted in the GCLLSG CLL3 protocol is a feasible and effective therapy option for younger patients with poor-risk CLL. Purpose of the present analysis was to study the impact of FISH karyotype according to the hierarchical model, and of IGHV mutational status on progression-free (PFS) and overall survival (OS) in this trial. Trial design and patients: The protocol comprised optional cytoreduction with CHOP, fludarabine, or FC; PBSC mobilization using the Dexa-BEAM regimen; and myeloablative therapy with TBI/CY followed by reinfusion of purged (CD34+) stem cells. Inclusion criteria were age 〈 61 years, stage Binet B/C or poor-risk stage A as defined by short lymphocyte doubling time plus elevated TK, and one line of pretreatment or less. From December 1996 through September 2002, 216 patients were registered with the protocol. As 47 cases had to be excluded due to screening failure (n=21), withdrawn consent (n=19) or other reasons (n=7), 169 patients were eligible for the current analysis. Male to female ratio was 5:1 and the median age at diagnosis was 51 years (range 27-60). Results: SCT was performed in 131 patients (78%) at a median time of 17 months (range 4-159) after initial diagnosis, whereas 38 patients did not proceed to SCT due to mobilization failure (n=14), disease progression (n=4), early death (n=3), patients preference (n=6), or unknown reasons (n=11). At a median follow-up of 99 months (range 4-137) after initiation of first cytoreductive therapy within the protocol, median OS of all 169 patients was 10.5 years, with 10.5 years for those treated with and 6.1 years for those treated without autoSCT, yielding a hazard ratio of 0.26 (95% CI 0.13-0.54; p 〈 .0001). Median PFS was 6.3 years, with 6.8 years for those treated with and 4.8 years for those treated without autoSCT (HR 0.39; 95% CI 0.23-0.67; p=0.0007). The 10-year incidence rate of t-MDS/ t-AML was 9% (1-18%). Diagnostic samples for assessment of the IGHV mutational status were available for 143 of 169 patients (85%). An unfavorable (unmutated of V3-21-containing) IGHV rearrangement was present in 104 patients (73%). Compared to the 39 patients with favorable IGHV, those with unfavorable VH had significantly worse PFS and OS (median PFS 5.1 years vs not reached, hazard ratio (HR) 2.47 (1.56-3.92), p=0.0001; median OS 9.1 years vs not reached, HR 2.0 (1.14-3.68), p=0.017). FISH was possible in 160 patients (95%) with results as follows: del 17p- 4 patients (3%), del 11q- without del 17p 40 patients (25%), trisomy 12 without del 17p- and del 11q- 20 patients (13%), del 13q- as sole abnormality 48 patients (30%), other karyotypes 20 patients (13%), normal karyotype 28 patients (17%). All 4 patients with del 17p- showed progressive disease after Dexa-BEAM mobilization and did not proceed to autoSCT. Whereas PFS (p 〈 0.0001) and OS (p 〈 0.0001) thus was strongly reduced in the 4 patients with del 17p-, no significant differences between the other subsets became evident: median PFS 1.0 years (del 17p-), 5.9 years (del 11q), 4.8 years (+12), 7.5 years (del 13q-), 7.7 years (normal); median OS 1.5 years (del 17p-), 10.5 years (del 11q-), not reached (+12), not reached (del 13q-), 10.3 years (normal). Conclusions: Unmutated IGHV remains an adverse prognostic factor after dose-escalated first-line therapy with autoSCT. In contrast, this strategy may overcome the unfavorable impact of the FISH karyotype del 11q- seen with conventional therapy. Disclosures: Hopfinger: Roche: Honoraria. Schmitz:Roche: Honoraria, Research Funding. Stilgenbauer:BayerScheringAG: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 2
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3666-3666
    Abstract: Abstract 3666 Introduction With the FDA and EMA approval of Bendamustine a new treatment option has recently become available to patients (pts) with indolent (low-grade) non-Hodgkin lymphoma (iNHL). Clinical registries provide insight into real-life treatment of pts. They can help to answer the question whether patients may benefit from new research findings. Methods The clinical registry on lymphoid neoplasms (TLN Registry), conducted by iOMEDICO in collaboration with the Arbeitskreis Klinische Studien (AKS) and the Kompetenznetz Maligne Lymphome (KML), prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered in hematology outpatient centres in Germany. Pts are followed for 5 years. A broad set of data regarding patient and tumor characteristics, comorbidities, all systemic treatments, response rates, progression-free survival and overall survival are recorded. Since May 2009, 106 sites have actively recruited a total of 2579 pts. Results From the overall sample, 645 pts received systemic 1st-line treatment for indolent Non-Hodgkin lymphoma (iNHL). 53% of pts are male, mean age at time of primary diagnosis was 65 years (yrs) and at start of therapy 66 yrs. Tumor stage was 7% Stage I, 15% Stage II, 25% Stage III and 54% Stage IV. 61% of pts (n=387) were diagnosed with at least one comorbidity, mainly hypertension (33%) or diabetes (12%); the average Charlson Comorbity Index of 0.6 indicates that pts have few comorbities. Rituximab is part of the 1st-line treatment in 94% (n=606) of pts with iNHL. Bendamustine is part of the 1st-line treatment in 71% (n=455) of pts with iNHL. It is mostly applied in combination with Rituximab (BR, 66%, n=428). Further 2% (n=10) receive Bendamustin as monotherapy. Rituximab/Cyclophosphamide/Doxorubicin/Vincristine/Prednisone (R-CHOP) as 1st-line treatment is applied in 16% (n=105) of pts with iNHL. Pts receiving BR or R-CHOP differ. Pts characteristics indicate that BR is applied preferably in elderly pts (mean 67.3 vs. 60.9 yrs). However, BR is the preferred treatment also in pts younger than 66 yrs (60% vs. 23%). The use of BR has increased from 62% in 2009 to 68% in 2011, whereas the rate of R-CHOP has decreased from 19% in 2009 to 15% in 2011. Of all pts with iNHL, 121 have received 2nd-line treatment. Rituximab is part of the 2nd-line treatment in 84% (n=102) of pts with iNHL. Bendamustine is part of the 2nd-line treatment in 68% (n=82) of pts with iNHL. It is mostly applied in combination with Rituximab (BR, 60%, n=72). Further 7% (n=9) receive Bendamustin as monotherapy. R-CHOP as 2nd-line treatment is applied in 7% (n=9) of pts with iNHL. Conclusion BR is the most frequently used systemic treatment for pts with iNHL in German hematology outpatient centres. The use of BR has continuously increased since 2009. In contrast, the use of R-CHOP has decreased. This indicates that in Germany R-CHOP can no longer be considered as “standard of care” for pts with iNHL. These data also show that results from clinical trials are quickly implemented into daily practice. The impact of BR on quality of life and survival remains to be of central interest in the future. Disclosures: Knauf: Mundipharma GmbH: Honoraria, Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 3
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4605-4605
    Abstract: Abstract 4605 Introduction With the FDA and EMA approval of Bendamustine and Rituximab new treatment options have recently become available to patients (pts) with chronic lymphocytic leukemia (CLL). Clinical registries provide insight into real-life treatment of pts. They can help to answer the question whether patients may benefit from new research findings. Methods The clinical registry on lymphoid neoplasms (TLN Registry), conducted by iOMEDICO in collaboration with the Arbeitskreis Klinische Studien (AKS) and the Kompetenznetz Maligne Lymphome (KML), prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered in hematology outpatient centres in Germany. Pts are followed for 5 years. A broad set of data regarding patient and tumor characteristics, comorbidities, all systemic treatments, response rates, progression-free survival and overall survival are recorded. Since May 2009, 106 sites have actively recruited a total of 2579 pts. Results From the overall sample, 420 pts received systemic 1st-line treatment for CLL. 65% of pts are male, mean age at time of primary diagnosis was 66 years (yrs) and at start of therapy 69 yrs. Tumor stage was 20% Binet A, 35% Binet B and 45% Binet C. 68% of pts (n=285) were diagnosed with at least one comorbidity, mainly hypertension (37%) or diabetes (15%); the average Charlson Comorbity Index of 0.7 indicates that overall pts have few comorbities. Rituximab is part of the 1st-line treatment in 82% (n=345) of pts with CLL. Bendamustine is part of the 1st-line treatment in 59% (n=247) of pts with CLL. It is mostly applied in combination with Rituximab (BR, 51%, n=213). Further 7% (n=28) receive Bendamustin as monotherapy. Fludarabine is part of the 1st-line treatment in 31% (n=132) of pts with CLL. It is applied in combination with Cyclophosphamide and Rituximab (FCR, 25%, n=103), as monotherapy (4%, n=15) or in combination with Cyclophosphamide (FC, 1%, n=6). Chlorambucil is part of the 1st-line treatment in 7% (n=31) of pts with CLL. It is applied as monotherapy (4%, n=15) or in combination with Rituximab (2%, n=10). Pts receiving BR, FCR or Chlorambucil differ. Pts characteristics indicate that BR and Chlorambucil are applied preferably in elderly pts (mean 70.1 (BR) vs. 75.7 (Chlorambucil) vs. 63.4 (FCR) yrs). Also, BR is given preferably in advanced stages of the disease as compared to FCR (Binet C 49% vs. 34%). The use of BR has increased from 41% in 2009 to 57% in 2011, while the use of FCR has decreased from 33% in 2009 to 17% in 2011. Of all pts with CLL in the TLN, 181 have received 2nd-line treatment. Rituximab is part of the 2nd-line treatment in 76% (n=137) of pts with CLL. Bendamustine is part of the 2nd-line treatment in 66% (n=120) of pts with CLL. It is mostly applied in combination with Rituximab (BR, 56%, n=101). Further 10% (n=18) receive Bendamustin as monotherapy. Fludarabine is part of the 2nd-line treatment in 20% (n=37) of pts with CLL. It is applied in combination with Cyclophosphamide and Rituximab (FCR, 10%, n=18), as monotherapy (5%, n=9) or in combination with Cyclophosphamide (FC, 3%, n=5). Chlorambucil is part of the 2nd-line treatment in 4% (n=7) of pts with CLL. It is mostly applied in combination with Rituximab (2%, n=4). Conclusion Rituximab and Bendamustine are the most frequently used drugs for the treatment of CLL in German hematology outpatient centres. The use or BR has significantly increased since 2009. In contrast, the use of FCR has decreased and only a minority of pts receive Chlorambucil. This indicates that in Germany Chlorambucil is no longer considered the “standard of care” for elderly pts with CLL. These data also show that results from clinical trials are quickly implemented into daily practice. The impact of these new treatment options on quality of life and survival remains to be of central interest in the future. Disclosures: Knauf: Mundipharma GmbH: Honoraria, Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publication Date: 2012
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  • 4
    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
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    Publication Date: 2008
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  • 5
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 2043-2043
    Abstract: Introduction: Bendamustine (BEN) is a purine analog / alkylator hybrid agent with a particular mechanisms of action that provides effective treatment for a number of hematologic and non-hematologic malignancies. It is used primarily for chemo-naïve, relapsed or refractory B-CLL as well as for other types of non-Hodgkin’s lymphomas. The aim of this randomized phase III, open-label, multicenter study was to compare the efficacy and safety of BEN versus chlorambucil (CLB) in treatment-naïve patients (pts) with B-CLL Binet stage B/C. Patients and Methods: Pts with untreated B-CLL were randomized to receive BEN (100 mg/m2 on days 1+2) or CLB (0.8 mg/kg on days 1+15) for up to 6 treatment cycles. Primary endpoints were overall remission rate (ORR), defined as complete response (CR), nodular partial response (nPR) and partial response (PR), confirmed after 8 weeks, and progression-free survival (PFS). Secondary endpoints were duration of remission, overall survival (OS), safety, and quality of life (QoL). Follow-up was for ≥12 months after completion of treatment of the last patient, or until progression for pts with CR, nPR or PR and stable disease, or until death or lost to follow-up. A 5-stage, adaptive-group, sequential procedure was used with planned interim analyses to adjust the number of pts. Safety and efficacy were assessed by an Independent Data Monitoring Committee. Results: 305 pts were randomized to receive BEN (n=156) or CLB (n=149). As 7 pts did not receive study medication, 298 pts were included in the safety analysis. At the time of this analysis, 264 pts (139 BEN; 125 CLB) were available for the efficacy analysis. For both treatment groups: median age was 64 years; 70% had Binet stage B and 30% Binet stage C disease; median number of cycles/patient was 6; median follow-up was 18.5 months. ORR was significantly higher with BEN than with CLB (68% vs 39%; p & lt;0.0001), with a CR of 30% vs 2%, respectively. Among the subgroups with Binet stage B and C disease, ORR was 70% and 61%, respectively, with BEN, vs 47% and 22%, respectively, with CLB. Median PFS (Kaplan-Meier estimate) was 21.7 months with BEN and 9.3 months with CLB (p & lt;0.0001), and median duration of remission was 18.9 months with BEN and 6.1 months with CLB (p & lt;0.0001). No difference in OS was seen between groups. Toxicity of BEN was manageable and did not impair QoL when compared with CLB. Infection rates (common toxicity criteria grades III+IV) were low in both groups (5.8% BEN; 3.5% CLB). Conclusions: BEN was significantly more effective than CLB in achieving remissions in treatment-naïve pts with B-CLL Binet stage B/C; median PFS and duration of remission were also significantly longer. Furthermore, safety data indicate that BEN toxicities are manageable and the drug is well tolerated. On the basis of these results, BEN should be considered as first-line chemotherapy for patients with B-CLL Binet stage B or C.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 6
    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
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    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 7
    Online Resource
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    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 4817-4817
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 4817-4817
    Abstract: Introduction: Bendamustine (BEN) provides effective treatment of hematologic as well as of non-hematologic malignancies. It is characterized by an unique activity profile which differs from common nitrogen mustard drugs. In particular, it causes only partial cross resistance to other alkylating agents, anthracyclines and anti-metabolites, respectively. BEN is used in patients with chemo naïve, relapsed or refractory chronic lymphocytic leukemia (CLL), however, no head-to-head study has been performed so far. Therefore, a multicenter, international phase III study was initiated to compare the activity of BEN against chlorambucil in treatment-naive B-CLL patients with Binet stage B/C. Patients and Methods: Patients are randomized to either Arm A (BEN 100 mg/m2, d 1+2) or to Arm B (chlorambucil 0,8mg/kg Broca’s weight, d 1+15) to receive a maximum of 6 treatment cycles. Primary objectives are overall remission rate and progression-free survival. The anticipated effects are an overall remission rate of 60% vs. 30% and a median progression free survival of 20 vs.14 months. Secondary objectives are additional efficacy parameters, safety, and quality of life. The study design is adaptive with four interim analyses to adjust the final number of patients, plus one safety analysis. A maximum of 350 patients is planned. Toxicities regarding hemoglobin, platelets and neutrophils are graded according to the NCIWG for CLL, while leukocyte and lymphocyte counts are graded according to CTC as in many other CLL trials. Results and Summary: To assess safety, twenty patients in each treatment arm with at least one completed treatment cycle have been evaluated. The results have been reviewed by an independent data monitoring committee (IDMC). It was concluded that the dosages selected for both treatment arms are safe and that the study is to be continued. Furthermore, another safety analysis was performed with respect to the rate of major infections in the same patient cohort after having completed study treatment. While the infection rate has been reported to be 29% in patients treated with fludarabine as published by Rai et al., in our study two BEN-patients (10%) experienced major infections whereas none occurred in the chlorambucil arm. One BEN-patient developed fever CTC grade 3 without neutropenia. Another patient experienced pneumonia CTC grade 2 requiring hospitalization and intravenous antibiotic treatment. In the BEN-arm, 87% of the scheduled dose was applied whereas 89% was given in the chlorambucil arm. Patients treated with BEN remained longer on study as compared to the chlorambucil patients. The toxicity rate, both hematologic and non-hematologic, was in favour for chlorambucil. In total, three patients were withdrawn from study due to toxicity: one patient in each treatment arm due to infection and one BEN-patient due to an allergic reaction. Meanwhile, the first planned interim analysis on remission rate was done. 43 patients in each treatment arm were evaluated. The IDMC recommended to continue the study. A second interim analysis will be performed after 160 patients will have completed the first tumor evaluation to adjust the number of patients finally required.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publication Date: 2004
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  • 8
    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.
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    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 9
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 5109-5109
    Abstract: Objectives This study was performed to investigate efficacy and tolerability of VEL under routine conditions in patients (pts.) with MM, who have received at least 1 previous line of therapy and are refractory to or have relapsed after their last therapy. Methods Pts. were treated up to 24 weeks with the recommended dose of VEL (1.3 mg/m2 day 1, 4, 8, 11 q3weeks). Any further diagnostic and therapeutic instructions were not provided in the protocol. At baseline, demographical and medical history data were collected, including type and number of preceding therapies and concomitant diseases. Adverse events (AEs) were continuously documented. Final data analysis is presented here. Results A total of n=50 pts. (27 female, 23 male) were included in 14 German OBHs. Median age was 68 years (yrs.), whereby 19 pts. were & gt; 70 yrs. old. A median of 1295 days (d) (range: 49–6201 d) passed between initial diagnosis and start of VEL therapy. Pts. had received a median of 2 prior treatments. Most frequently reported concomitant diseases were hypertension in 36.0% of the pts., renal failure in 28.0% and coronary heart disease in 14.0%, as well as heart failure in 8.0%. Overall, 10.0% of the pts. exhibited a PNP at the start of therapy (6.0% grade 1 without pain; 4.0% without indication of the degree of severity). Up to now assessment of response is available in 39/50 pts., with 2 CR, 22 PR, 7 MR, 6 SD and 2 PD. The overall response rate (CR+PR+MR) was 79,4%. Time to best response (CR+PR+MR) was median 3 cycles (range 1–7), while in 3 pts. best response was achieved after 1 cycle. At end of study, a total of 458 AEs were documented (9.6% classified grade 3; 2.6% grade 4). The investigators assessed 242 AEs (52.8%) as related to VEL and most frequently documented: thrombocytopenia (18.2%), anemia (16.9%), leukocytopenia (9.9%), neuropathy/paresthesia (9.1%), vomiting/nausea (6.6%), asthenia (5.0%) and diarrhea (4.1%). A total of 34/458 AEs (5.5%) were classified as serious, with 14 (41.2%) of them related to the VEL therapy according to the investigator’s opinion. 2 pts. (4.0 %) died in the course of the trial (deaths not related to VEL). Safety data are under ongoing assessment. Conclusion VEL therapy in an unselected, pretreated group of MM pts. is effective and well tolerated. Findings of this non-interventional study confirm efficacy and safety results of large randomized clinical trials. Thus the use of VEL is also suitable under routine conditions in office-based hematology units.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    Language: Unknown
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 10
    Online Resource
    Online Resource
    S. Karger AG ; 2009
    In:  Oncology Research and Treatment Vol. 32, No. 4 ( 2009), p. 175-180
    In: Oncology Research and Treatment, S. Karger AG, Vol. 32, No. 4 ( 2009), p. 175-180
    Type of Medium: Online Resource
    ISSN: 2296-5270 , 2296-5262
    Language: Unknown
    Publisher: S. Karger AG
    Publication Date: 2009
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