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Pieter Sonneveld - One of the best experts on this subject based on the ideXlab platform.
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retrospective matched pairs analysis of Bortezomib plus dexamethasone versus Bortezomib monotherapy in relapsed multiple myeloma
Haematologica, 2015Co-Authors: Meletios A. Dimopoulos, Robert Z Orlowski, Pieter Sonneveld, Thierry Facon, Kenneth C. Anderson, Meral Beksac, Lotfi Benboubker, Huw Roddie, Anna Potamianou, Catherine CouturierAbstract:Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent Bortezomib are lacking. This retrospective analysis compared second-line treatment with Bortezomib-dexamethasone and Bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after Bortezomib dosing. Median Bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with Bortezomib-dexamethasone and Bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P<0.001), and median time-to-progression (13.6 vs. 7.0 months; hazard ratio [HR]=0.394; P=0.003) and progression-free survival (11.9 vs. 6.4 months; HR=0.595; P=0.051) were longer with Bortezomib-dexamethasone versus Bortezomib, respectively. Rates of any-grade adverse events, most common grade 3 or higher adverse events, and discontinuations due to adverse events appeared similar between the groups. Two patients per group died of treatment-related adverse events. These data indicate the potential benefit of Bortezomib-dexamethasone compared with single-agent Bortezomib at first relapse in myeloma. The MMY-2045, APEX, and DOXIL-MMY-3001 clinical trials were registered at, respectively, clinicaltrials.gov identifier: 00908232, 00048230, and 00103506.
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Retrospective matched-pairs analysis of Bortezomib plus dexamethasone versus Bortezomib monotherapy in relapsed multiple myeloma
Haematologica, 2014Co-Authors: Meletios A. Dimopoulos, Robert Z Orlowski, Pieter Sonneveld, Thierry Facon, Kenneth C. Anderson, Meral Beksac, Lotfi Benboubker, Huw Roddie, Anna Potamianou, Catherine CouturierAbstract:Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent Bortezomib are lacking. This retrospective analysis compared second-line treatment with Bortezomib-dexamethasone and Bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after Bortezomib dosing. Median Bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with Bortezomib-dexamethasone and Bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P
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Bortezomib based versus nonBortezomib based induction treatment before autologous stem cell transplantation in patients with previously untreated multiple myeloma a meta analysis of phase iii randomized controlled trials
Journal of Clinical Oncology, 2013Co-Authors: Pieter Sonneveld, Joan Blade, Juan Jose Lahuerta, Hartmut Goldschmidt, Laura Rosinol, Michele Cavo, Paola Tacchetti, Elena Zamagni, Michel Attal, Henk M LokhorstAbstract:Purpose To characterize efficacy and safety of Bortezomib-based versus nonBortezomib-based induction regimens through an integrated analysis of data from phase III studies in transplantation-eligible patients with previously untreated myeloma. Patients and Methods Patient-level data from the IFM 2005-01 (Bortezomib-dexamethasone v vincristine-doxorubicin-dexamethasone [VAD] induction), HOVON-65/GMMG-HD4 (Bortezomib-doxorubicin-dexamethasone v VAD), and PETHEMA GEM05MENOS65 (Bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) studies were pooled in an integrated analysis of efficacy and safety. Study-level data from the GIMEMA MM-BO2005 study (Bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) supplemented the integrated patient-level analysis. Key efficacy end points were post-transplantation complete plus near-complete response (CR+nCR) rate and progression-free survival (PFS). Results Patient-level data for 1,572 patients (Bortezomib-based induction, n = 787; nonBortezomib-b...
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Bortezomib based versus nonBortezomib based induction treatment before autologous stem cell transplantation in patients with previously untreated multiple myeloma a meta analysis of phase iii randomized controlled trials
Journal of Clinical Oncology, 2013Co-Authors: Pieter Sonneveld, Joan Blade, Juan Jose Lahuerta, Hartmut Goldschmidt, Laura Rosinol, Michele Cavo, Paola Tacchetti, Elena Zamagni, Michel Attal, Henk M LokhorstAbstract:Purpose To characterize efficacy and safety of Bortezomib-based versus nonBortezomib-based induction regimens through an integrated analysis of data from phase III studies in transplantation-eligible patients with previously untreated myeloma. Patients and Methods Patient-level data from the IFM 2005-01 (Bortezomib-dexamethasone v vincristine-doxorubicin-dexamethasone [VAD] induction), HOVON-65/GMMG-HD4 (Bortezomib-doxorubicin-dexamethasone v VAD), and PETHEMA GEM05MENOS65 (Bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) studies were pooled in an integrated analysis of efficacy and safety. Study-level data from the GIMEMA MM-BO2005 study (Bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) supplemented the integrated patient-level analysis. Key efficacy end points were post-transplantation complete plus near-complete response (CR+nCR) rate and progression-free survival (PFS). Results Patient-level data for 1,572 patients (Bortezomib-based induction, n = 787; nonBortezomib-b...
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Bortezomib-induced polyneuropathy
The Netherlands journal of medicine, 2013Co-Authors: A. J J Rampen, Pieter Sonneveld, Joost L. M. Jongen, Irene Van Heuvel, Marjan Scheltens-de Boer, Martin J. Van Den BentAbstract:BACKGROUND Peripheral neuropathy is a frequent side effect of Bortezomib chemotherapy. Relatively little is known about the clinical characteristics of this neuropathy, especially with respect to pain. Our aim was to describe the clinical characteristics and course of Bortezomib-induced polyneuropathy. METHODS This is a retrospective cohort study of 39 patients diagnosed with Bortezomib-induced polyneuropathy. RESULTS Pain is the most prominent symptom and 14 of 39 patients suffered from severe pain. More than 50% of our patients used analgesics due to moderate or severe pain. We found no correlation between severity of symptoms of Bortezomib-induced polyneuropathy and cumulative dose or dose intensity of Bortezomib. Nerve conduction studies did not correlate well with symptom severity. Dose reduction or discontinuation of treatment reduced severity in most cases. CONCLUSION Painful polyneuropathy is a frequent, dose-limiting side effect of Bortezomib with a relatively good prognosis. Careful neurological monitoring of symptoms and timely dose adjustment is important.
Meletios A. Dimopoulos - One of the best experts on this subject based on the ideXlab platform.
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overall survival of patients with relapsed multiple myeloma treated with panobinostat or placebo plus Bortezomib and dexamethasone the panorama 1 trial a randomised placebo controlled phase 3 trial
The Lancet Haematology, 2016Co-Authors: Jesus F Sanmiguel, Meletios A. Dimopoulos, Meral Beksac, Vania T M Hungria, Sungsoo Yoon, Ashraf Elghandour, Wieslaw Wiktor Jedrzejczak, Andreas Gunther, Thanyaphong Na Nakorn, Noppadol SiritanaratkulAbstract:Summary Background Panobinostat plus Bortezomib and dexamethasone significantly increased median progression-free survival compared with placebo plus Bortezomib and dexamethasone in the phase 3 PANORAMA 1 trial. Here, we present the final overall survival analysis for this trial. Methods PANORAMA 1 is a randomised, placebo-controlled, double-blind, phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma with one to three previous treatments. Patients were randomly assigned (1:1) to receive panobinostat (20 mg orally) or placebo, with Bortezomib (1·3 mg/m 2 intravenously) and dexamethasone (20 mg orally), over two distinct treatment phases. In treatment phase 1 (eight 3-week cycles), patients received: panobinostat or placebo on days 1, 3, 5, 8, 10, and 12; Bortezomib on days 1, 4, 8, and 11; and dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12. During treatment phase 2 (four 6-week cycles with a 2 weeks on, 1 week off schedule), panobinostat or placebo was given three times a week, Bortezomib was administered once a week, and dexamethasone was given on the days of and following Bortezomib administration. The primary endpoint was progression-free survival; overall survival was a key secondary endpoint. This study is registered at ClinicalTrials.gov, NCT01023308. Findings Between Jan 21, 2010, and Feb 29, 2012, 768 patients were enrolled into the study and randomly assigned to receive either panobinostat (n=387) or placebo (n=381), plus Bortezomib and dexamethasone. At data cutoff (June 29, 2015), 415 patients had died. Median overall survival was 40·3 months (95% CI 35·0–44·8) in those who received panobinostat, Bortezomib, and dexamethasone versus 35·8 months (29·0–40·6) in those who received placebo, Bortezomib, and dexamethasone (hazard ratio [HR] 0·94, 95% CI 0·78–1·14; p=0·54). Of patients who had received at least two previous regimens including Bortezomib and an immunomodulatory drug, median overall survival was 25·5 months (95% CI 19·6–34·3) in 73 patients who received panobinostat, Bortezomib, and dexamethasone versus 19·5 months (14·1–32·5) in 74 who received placebo (HR 1·01, 95% CI 0·68–1·50). Interpretation The overall survival benefit with panobinostat over placebo with Bortezomib and dexamethasone was modest. However, optimisation of the regimen could potentially prolong treatment duration and improve patients' outcomes, although further trials will be required to confirm this. Funding Novartis Pharmaceuticals.
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retrospective matched pairs analysis of Bortezomib plus dexamethasone versus Bortezomib monotherapy in relapsed multiple myeloma
Haematologica, 2015Co-Authors: Meletios A. Dimopoulos, Robert Z Orlowski, Pieter Sonneveld, Thierry Facon, Kenneth C. Anderson, Meral Beksac, Lotfi Benboubker, Huw Roddie, Anna Potamianou, Catherine CouturierAbstract:Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent Bortezomib are lacking. This retrospective analysis compared second-line treatment with Bortezomib-dexamethasone and Bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after Bortezomib dosing. Median Bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with Bortezomib-dexamethasone and Bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P<0.001), and median time-to-progression (13.6 vs. 7.0 months; hazard ratio [HR]=0.394; P=0.003) and progression-free survival (11.9 vs. 6.4 months; HR=0.595; P=0.051) were longer with Bortezomib-dexamethasone versus Bortezomib, respectively. Rates of any-grade adverse events, most common grade 3 or higher adverse events, and discontinuations due to adverse events appeared similar between the groups. Two patients per group died of treatment-related adverse events. These data indicate the potential benefit of Bortezomib-dexamethasone compared with single-agent Bortezomib at first relapse in myeloma. The MMY-2045, APEX, and DOXIL-MMY-3001 clinical trials were registered at, respectively, clinicaltrials.gov identifier: 00908232, 00048230, and 00103506.
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Retrospective matched-pairs analysis of Bortezomib plus dexamethasone versus Bortezomib monotherapy in relapsed multiple myeloma
Haematologica, 2014Co-Authors: Meletios A. Dimopoulos, Robert Z Orlowski, Pieter Sonneveld, Thierry Facon, Kenneth C. Anderson, Meral Beksac, Lotfi Benboubker, Huw Roddie, Anna Potamianou, Catherine CouturierAbstract:Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent Bortezomib are lacking. This retrospective analysis compared second-line treatment with Bortezomib-dexamethasone and Bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after Bortezomib dosing. Median Bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with Bortezomib-dexamethasone and Bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P
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Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma
The New England Journal of Medicine, 2008Co-Authors: Jesus San F Miguel, Meletios A. Dimopoulos, Rudolf Schlag, Nuriet K Khuageva, Ofer Shpilberg, Martin Kropff, Ivan Spicka, Maria Teresa Petrucci, Antonio Palumbo, Olga SamoilovaAbstract:The time to progression among patients receiving Bortezomib plus melphalan– prednisone (Bortezomib group) was 24.0 months, as compared with 16.6 months among those receiving melphalan–prednisone alone (control group) (hazard ratio for the Bortezomib group, 0.48; P<0.001). The proportions of patients with a partial response or better were 71% in the Bortezomib group and 35% in the control group; complete-response rates were 30% and 4%, respectively (P<0.001). The median duration of the response was 19.9 months in the Bortezomib group and 13.1 months in the control group. The hazard ratio for overall survival was 0.61 for the Bortezomib group (P = 0.008). Adverse events were consistent with established profiles of toxic events associated with Bortezomib and melphalan–prednisone. Grade 3 events occurred in a higher proportion of patients in the Bortezomib group than in the control group (53% vs. 44%, P = 0.02), but there were no significant differences in grade 4 events (28% and 27%, respectively) or treatment-related deaths (1% and 2%). Conclusions Bortezomib plus melphalan–prednisone was superior to melphalan–prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.)
Robert Z Orlowski - One of the best experts on this subject based on the ideXlab platform.
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retrospective matched pairs analysis of Bortezomib plus dexamethasone versus Bortezomib monotherapy in relapsed multiple myeloma
Haematologica, 2015Co-Authors: Meletios A. Dimopoulos, Robert Z Orlowski, Pieter Sonneveld, Thierry Facon, Kenneth C. Anderson, Meral Beksac, Lotfi Benboubker, Huw Roddie, Anna Potamianou, Catherine CouturierAbstract:Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent Bortezomib are lacking. This retrospective analysis compared second-line treatment with Bortezomib-dexamethasone and Bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after Bortezomib dosing. Median Bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with Bortezomib-dexamethasone and Bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P<0.001), and median time-to-progression (13.6 vs. 7.0 months; hazard ratio [HR]=0.394; P=0.003) and progression-free survival (11.9 vs. 6.4 months; HR=0.595; P=0.051) were longer with Bortezomib-dexamethasone versus Bortezomib, respectively. Rates of any-grade adverse events, most common grade 3 or higher adverse events, and discontinuations due to adverse events appeared similar between the groups. Two patients per group died of treatment-related adverse events. These data indicate the potential benefit of Bortezomib-dexamethasone compared with single-agent Bortezomib at first relapse in myeloma. The MMY-2045, APEX, and DOXIL-MMY-3001 clinical trials were registered at, respectively, clinicaltrials.gov identifier: 00908232, 00048230, and 00103506.
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Retrospective matched-pairs analysis of Bortezomib plus dexamethasone versus Bortezomib monotherapy in relapsed multiple myeloma
Haematologica, 2014Co-Authors: Meletios A. Dimopoulos, Robert Z Orlowski, Pieter Sonneveld, Thierry Facon, Kenneth C. Anderson, Meral Beksac, Lotfi Benboubker, Huw Roddie, Anna Potamianou, Catherine CouturierAbstract:Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent Bortezomib are lacking. This retrospective analysis compared second-line treatment with Bortezomib-dexamethasone and Bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after Bortezomib dosing. Median Bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with Bortezomib-dexamethasone and Bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P
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Bortezomib in relapsed and relapsed/ refractory multiple myeloma
Bortezomib in the Treatment of Multiple Myeloma, 2010Co-Authors: Jatin J. Shah, Robert Z OrlowskiAbstract:Proteasome inhibition was validated as a rational therapeutic approach when Bortezomib (VELCADE®), the first-in-class proteasome inhibitor, was approved by the Food and Drug Administration in 2003. This initial approval, which was for multiple myeloma patients who had received at least two prior therapies, and whose disease had demonstrated progression on the last of these, also made Bortezomib the first new agent to be available for myeloma in over a decade. Since that time, further studies of Bortezomib both alone, and as part of rationally designed, molecularly based combination regimens, have shown the versatility of this agent, and made it a universally accepted standard of care. Importantly, this use of Bortezomib has been associated with ever increasing overall response rates and response qualities, and, most importantly, long-term outcome measures, including overall survival. These findings have rightfully entrenched Bortezomib as one of the most important parts of our chemotherapeutic armamentarium against multiple myeloma. In this chapter, we will review the role of Bortezomib as a single-agent, and in combination with other chemotherapeutics, to combat myeloma in the relapsed and relapsed/refractory settings. Also, emerging data about retreatment with Bortezomib will be presented to provide insights into the possible role of this agent in the modern era, in which patients may have already been previously treated as part of induction therapy with Bortezomib. Finally, approaches that show promise to overcome primary or secondary resistance to Bortezomib will be examined, to determine if this agent may be of benefit in a number of myeloma settings in each individual patient.
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randomized phase iii study of pegylated liposomal doxorubicin plus Bortezomib compared with Bortezomib alone in relapsed or refractory multiple myeloma combination therapy improves time to progression
Journal of Clinical Oncology, 2007Co-Authors: Robert Z Orlowski, Arnon Nagler, Pieter Sonneveld, Joan Blade, Roman Hajek, Andrew Spencer, Jesus San F Miguel, Tadeusz Robak, Anna Dmoszynska, Noemi HorvathAbstract:Purpose This phase III international study compared the efficacy and safety of a combination of pegylated liposomal doxorubicin (PLD) plus Bortezomib with Bortezomib monotherapy in patients with relapsed or refractory multiple myeloma. Patients and Methods Six hundred forty-six patients were randomly assigned to receive either intravenous Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of an every 21-days cycle, or the same Bortezomib regimen with PLD 30 mg/m2 on day 4. Results Median time to progression was increased from 6.5 months for Bortezomib to 9.3 months with the PLD + Bortezomib combination (P = .000004; hazard ratio, 1.82 [monotherapy v combination therapy]; 95% CI, 1.41 to 2.35). The 15-month survival rate for PLD + Bortezomib was 76% compared with 65% for Bortezomib alone (P = .03). The complete plus partial response rate was 41% for Bortezomib and 44% for PLD + Bortezomib, a difference that was not statistically significant. Median duration of response was increased from 7.0 to 10.2 months (P = ...
Catherine Couturier - One of the best experts on this subject based on the ideXlab platform.
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retrospective matched pairs analysis of Bortezomib plus dexamethasone versus Bortezomib monotherapy in relapsed multiple myeloma
Haematologica, 2015Co-Authors: Meletios A. Dimopoulos, Robert Z Orlowski, Pieter Sonneveld, Thierry Facon, Kenneth C. Anderson, Meral Beksac, Lotfi Benboubker, Huw Roddie, Anna Potamianou, Catherine CouturierAbstract:Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent Bortezomib are lacking. This retrospective analysis compared second-line treatment with Bortezomib-dexamethasone and Bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after Bortezomib dosing. Median Bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with Bortezomib-dexamethasone and Bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P<0.001), and median time-to-progression (13.6 vs. 7.0 months; hazard ratio [HR]=0.394; P=0.003) and progression-free survival (11.9 vs. 6.4 months; HR=0.595; P=0.051) were longer with Bortezomib-dexamethasone versus Bortezomib, respectively. Rates of any-grade adverse events, most common grade 3 or higher adverse events, and discontinuations due to adverse events appeared similar between the groups. Two patients per group died of treatment-related adverse events. These data indicate the potential benefit of Bortezomib-dexamethasone compared with single-agent Bortezomib at first relapse in myeloma. The MMY-2045, APEX, and DOXIL-MMY-3001 clinical trials were registered at, respectively, clinicaltrials.gov identifier: 00908232, 00048230, and 00103506.
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Retrospective matched-pairs analysis of Bortezomib plus dexamethasone versus Bortezomib monotherapy in relapsed multiple myeloma
Haematologica, 2014Co-Authors: Meletios A. Dimopoulos, Robert Z Orlowski, Pieter Sonneveld, Thierry Facon, Kenneth C. Anderson, Meral Beksac, Lotfi Benboubker, Huw Roddie, Anna Potamianou, Catherine CouturierAbstract:Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent Bortezomib are lacking. This retrospective analysis compared second-line treatment with Bortezomib-dexamethasone and Bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after Bortezomib dosing. Median Bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with Bortezomib-dexamethasone and Bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P
Kenneth C. Anderson - One of the best experts on this subject based on the ideXlab platform.
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retrospective matched pairs analysis of Bortezomib plus dexamethasone versus Bortezomib monotherapy in relapsed multiple myeloma
Haematologica, 2015Co-Authors: Meletios A. Dimopoulos, Robert Z Orlowski, Pieter Sonneveld, Thierry Facon, Kenneth C. Anderson, Meral Beksac, Lotfi Benboubker, Huw Roddie, Anna Potamianou, Catherine CouturierAbstract:Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent Bortezomib are lacking. This retrospective analysis compared second-line treatment with Bortezomib-dexamethasone and Bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after Bortezomib dosing. Median Bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with Bortezomib-dexamethasone and Bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P<0.001), and median time-to-progression (13.6 vs. 7.0 months; hazard ratio [HR]=0.394; P=0.003) and progression-free survival (11.9 vs. 6.4 months; HR=0.595; P=0.051) were longer with Bortezomib-dexamethasone versus Bortezomib, respectively. Rates of any-grade adverse events, most common grade 3 or higher adverse events, and discontinuations due to adverse events appeared similar between the groups. Two patients per group died of treatment-related adverse events. These data indicate the potential benefit of Bortezomib-dexamethasone compared with single-agent Bortezomib at first relapse in myeloma. The MMY-2045, APEX, and DOXIL-MMY-3001 clinical trials were registered at, respectively, clinicaltrials.gov identifier: 00908232, 00048230, and 00103506.
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Retrospective matched-pairs analysis of Bortezomib plus dexamethasone versus Bortezomib monotherapy in relapsed multiple myeloma
Haematologica, 2014Co-Authors: Meletios A. Dimopoulos, Robert Z Orlowski, Pieter Sonneveld, Thierry Facon, Kenneth C. Anderson, Meral Beksac, Lotfi Benboubker, Huw Roddie, Anna Potamianou, Catherine CouturierAbstract:Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent Bortezomib are lacking. This retrospective analysis compared second-line treatment with Bortezomib-dexamethasone and Bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after Bortezomib dosing. Median Bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with Bortezomib-dexamethasone and Bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P
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Bortezomib in the front-line treatment of multiple myeloma.
Expert review of anticancer therapy, 2008Co-Authors: Paul G Richardson, Teru Hideshima, Constantine S Mitsiades, Nikhil C Munshi, Robert L Schlossman, Irene M. Ghobrial, Kenneth C. AndersonAbstract:Front-line therapy for multiple myeloma is rapidly evolving with the development of new, highly active regimens based on novel agents such as Bortezomib. Bortezomib-based regimens are demonstrating substantial efficacy both as induction prior to stem cell transplantation and as treatment for patients ineligible for transplant, offering rapid and durable responses with consistently high rates of complete response, a surrogate end point for improved overall survival. Combinations of Bortezomib plus established and novel agents, such as melphalan-prednisone, dexamethasone, doxorubicin, thalidomide-dexamethasone and, most recently, lenalidomide-dexamethasone, are proving superior to or more promising than previous standards of care. Importantly, these regimens are demonstrating enhanced activity across the front-line population, including patients with renal impairment, high-risk cytogenetics and advanced bone disease. Impressive Phase 3 results with Bortezomib-melphalan-prednisone, Bortezomib-dexamethasone and Bortezomib-thalidomide-dexamethasone should facilitate the establishment of these highly effective regimens as key therapies for newly diagnosed myeloma.
