Economic Evaluation of Thalidomide Combined with Melphalan and Prednisone in Previously Untreated Multiple Myeloma in Scotland

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2395-2395 ◽  
Author(s):  
Baris Deniz ◽  
Thierry Facon ◽  
Ian Singer ◽  
Paul Micallef-Eynaud ◽  
Ian Joseph ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Event ◽  
Adverse Events ◽  
Health Outcomes ◽  
Progressive Disease ◽  
Life Time ◽  
Sensitivity Analyses ◽  
List Price ◽  
Model Parameters

Abstract INTRODUCTION: Thalidomide (Thalomid®/Thalidomide Pharmion®) combined with melphalan and prednisone (MPT) yields improved progression-free and overall survival compared to MP alone (Facon et. al., Lancet2007; 370:1191). This study was designed to estimate the life-time health and cost consequences of MPT versus MP in Scottish patients with previously untreated multiple myeloma. METHODS: A Markov model was developed to determine cost and health outcomes for a cohort of patients receiving a course of MPT or MP. The disease course was conceptualized by 4 mutually exclusive health states: pre-progression without adverse events, pre-progression with adverse event, progressive disease, and death. Probabilities of moving between these states (i.e. natural progression plus efficacy and safety of the treatments) were derived from a long-term randomized clinical trial, IFM 99-06 (Facon et. al., Lancet2007; 370:1191). Both patient cohorts remained on the assigned treatment for a maximum of twelve 6-week cycles, until progression or treatment-limiting toxicity. Treatment duration and the average daily dose were modelled to match IFM 99-06. During treatment, each cohort was exposed to adverse event risks associated with therapy estimated from IFM 99-06. Health state utilities associated with adverse events and disease states were obtained from the literature. Thalidomide cost was set at UK list price; routine disease-management costs by disease-state (progressive disease and remission state) reflect clinical practice in Scotland. As recommended by the UK treasury, costs and health outcomes were discounted at 3.5% per annum to adjust to present values. Univariate and multivariate sensitivity analyses were performed around key model parameters. RESULTS: The model estimated improvements in health outcomes with MPT with a median time to progression of 25 months vs. 12 months with MP. Estimated median overall survivals were 4.03 years vs. 2.88 years with MP. These results translate to a gain of 0.91 (3.24 vs. 2.32) quality-adjusted life-years (QALYs). MPT is associated with higher overall costs (£25,199 per patient) compared with MP (£8,935), over the modeled life-time, leading to an incremental cost-effectiveness ratio of £17,847 per QALY and £14,803 per life-year gained. Sensitivity analyses showed that results remained consistent through broad changes in model parameters including the addition of thromboembolic prophylaxis. CONCLUSIONS: MPT delivers improvements in progression-free and overall survival in a life-limiting orphan disease compared to MP and economic results fall within a range considered cost-effective in Scotland.

scholarly journals Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shenghao Wu ◽  
Cuiping Zheng ◽  
Songyan Chen ◽  
Xiaoping Cai ◽  
Yuejian Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Events ◽  
Subcutaneous Administration ◽  
Progression Free Survival ◽  
The Other ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen.Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively.Results. The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%,P=0.848) and progression-free survival (median 22 months versus 25 months;P=0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%,P=0.015).Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

High Dose Chemotherapy and Autologous Stem Cell Transplantation in Multiple Myeloma: Comparison of Four Preparative Regimens.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5489-5489
Author(s):  
Emilio P. Alessandrino ◽  
Letizia Zenone Bragotti ◽  
Anna A. Colombo ◽  
Alessandra Algarotti ◽  
Paolo Bernasconi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Total Dose ◽  
Stable Disease ◽  
Partial Remission ◽  
Progressive Disease ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Preparative Regimen

Abstract From 1996 to 2003, 113 consecutive patients with multiple myeloma were treated with four different high dose approaches rescued by autologous peripheral blood progenitor cells (PBPC) after four cycles of VAD or other combinations. The median age was 53 years 31–68), 58% were male and 42% female, the median interval from diagnosis to transplant was 252 days (range 160–3116 days). Twenty-five patients received as preparative regimen Carmustine, Etoposide and Melphalan (BVM) at the total dose of 600 mg/m2, 900mg/m2 and 140–180 mg m2 respectively. Nineteen pts had as preparative regimen Thiotepa and Melphalan at the total dose of 10 mg/kg and 140–180 mg/m2 respectively, 38 pts received a double transplant with Melphalan given as a single agent at the dose of 200 mg/m2, while 31 pts received a single transplant with Melphalan 200 mg/m2. In patients with poor performance status at transplant or previous history of infection or renal impairment, the dose of melphalan was reduced by 20% respect to the standard planned dose. in the group of 25patients treated by BVM, 10 had progressive disease, 6 stable disease (SD), 7 partial remission (PR), 1 very good partial remission (VGPR). At day +90 from transplant, 17 patients were in CR or PR (68%). The actuarial probability of overall survival and event free survival at 5 years were 40% and 20%, respectively. One pt died of transplant, one developed a solid tumor 24 mos after transplant. in the group of 19 pts treated with TT and Mel (TT-Mel), 3 pts were with progressive disease, 3 with stable disease, 6 in partial remission, 3 with minimal response, 3 in VGPR, 1 in CR. At day +90, 15 pts were in CR or PR (78%). The actuarial probability of survival was 50% at 5 years, and event free survival 28%. in the group of 38 pts who received a double transplant, 7 pts were with progressive disease, 3 with stable disease, 14 in PR, 12 in VGPR or CR. At day +90 after the second transplant, 31 of 38 patients (81%) were in CR or PR. Overall survival and event free survival was respectively 48% and 20% at five years. in the group of 31 pts receiving a single transplant with Melphalan alone, 8 were with progressive disease, 1 with stable disease, 6 in VGPR, 1 in CR, 13 in PR. At day +90, 21 of 31 patients (67%) were in CR or PR. Overall survival and event free survival was respectively 45% and 22% at five years. In conclusion, double transplant seems better than one transplant with melphalan alone in terms of EFS and OS (p<0.03); the BVM combination produces high response rates, the regimen, however, is toxic with a high rate of life threatening mucositis. the addition of Carmustine and Vepeside or Thiotepa to Melphalan does not produce significant improvement of OS and EFS.

Early Lymphocyte Recovery Predicts Superior Survival after Autologous Peripheral Blood Stem Cell Transplantation (ASCT) in Patients with Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5487-5487
Author(s):  
Devendra K. Hiwase ◽  
Anthony P. Schwarer ◽  
Geraldine M. Bollard ◽  
Smita D. Hiwase ◽  
Michael Bailey
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Prognostic Marker ◽  
Lymphocyte Count ◽  
Progressive Disease ◽  
Prognostic Indicator ◽  
Cell Transplant ◽  
The Difference

Abstract Aim: ASCT has improved survival in patients with multiple myeloma although most patients develop progressive disease. Absolute lymphocyte count recovery at day 15 (ALC-15) following ASCT has been reported as an independent prognostic indicator of overall survival (OS) and progression free survival (PFS) for patients with multiple myeloma. It is not only a good prognostic marker but may also have therapeutic significance. We evaluated absolute lymphocyte recovery on day 15 (ALC-15), day 30 (ALC-30), day 60 (ALC-60) as a prognostic marker following ASCT in patients with multiple myeloma. Method: Between 1992 and 2004, 119 consecutive patients underwent ASCT. ALC-15, ALC-30, ALC-60 were evaluated for impact on OS and PFS following ASCT. Information on known prognostic factors for multiple myeloma including age, BM plasma cells (PC), paraprotein (PP), international staging system (ISS staging) and disease response following stem cell transplant were also evaluated. Result: There were 119 (M/F, 79/43) patients and median age was 57 (30–70) years. Most patients (N=100) received melphalan 200 mg/m2 as conditioning chemotherapy. The median CD34 dose infused was 3.95 x 106/kg (1.30–33.7). Median ALC-15 was 190 (0–254) cells/ul, median ALC-30 was 1000 (60 to 5590) cells/ul and ALC-60 was 1290 (50–6570). There were 28% of patients in complete remission (CR) & 67% in partial remission (PR) following ASCT. On Multivariate analysis: ALC-30 was significantly associated with OS. Although there was higher PFS with higher lymphocyte count, the difference was not statistically significant. Other known prognostic factors such as ISS staging, PC at diagnosis, age at transplant and CR response following ASCT were also significantly correlated with OS & PFS. Survival analysis: Median OS was 64 (0.2 to 175) months and PFS 32 (1.7 to 175) months following PBSCT. In patients with ALC-30 &gt;500 cells/ul median OS was 80 months and 53 months in patients with ALC-30 &lt; 500 cells/ul (P= 0.0147). Fig 1: Overall survival following ASCT in months Fig 1:. Overall survival following ASCT in months PFS was 43 months in patients with ALC-30 &gt; 500 cells/ul and 31 months in patients with ALC-30 &lt; 500 cells/ul (P=0.39). Median ALC-30 was 1309 cells/ul in patients who were alive at last follow up while median ALC-30 was 879 cells/ul in patients who were deceased (P=0.0072) and in most of the patients (35/45, 77%) progressive disease was responsible for their demise. There was no significant correlation between CD34+ stem cells dose and lymphocyte dose in autograft with ALC-30 recovery (P=0.26). Conclusions: ALC-30 was an independent prognostic indicator of OS following ASCT in patients with multiple myeloma. There was trend for longer PFS in patients with ALC-30 &gt;500 cells/ul, although the difference was not statistically significant. This may be due small sample size and needs to be evaluated further in prospective study. We could not find a correlation between lymphocyte dose or CD34 dose in autograft with ALC-30 recovery. Lower ISS stage, less extensive marrow infiltration at diagnosis and complete response following PBSCT positively influences OS & PFS.

Incidence of serious adverse events in bortezomib, lenalidomide and bortezomib plus lenalidomide maintenance for multiple myeloma: Interim analysis of MMRF-CoMMpass study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19516-e19516
Author(s):  
Venkata Vosuri ◽  
Mark A Fiala ◽  
Wenners Ballard ◽  
Tanya Marya Wildes ◽  
Mark A. Schroeder ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Event ◽  
Stem Cell ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Incidence Rate ◽  
Interim Analysis ◽  
Therapy Group ◽  
Cell Transplant ◽  
Serious Adverse Events

e19516 Background: Autologous stem cell transplantation (ASCT) followed by maintenance therapy is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma. Maintenance typically consists of lenalidomide (LEN), however, bortezomib (BOR) and bortezomib-lenalidomide combination are other options. The respective toxicity of these regimens has not been well studied. We performed secondary data analysis to compare incidence of serious adverse events associated with each maintenance therapy group during post-ASCT maintenance treatment period. Methods: Data was extracted from the open-access MMRF Researcher Gateway corresponding with interim analysis from the CoMMpass study. We extracted data of first-time autologous stem cell transplant patients who completed maintenance therapy post-ASCT. We categorized patients into three sub groups bortezomib, lenalidomide or combination (bortezomib and lenalidomide) maintenance therapy. Incidence rate for serious adverse events (grade 3 or higher) was calculated by number of events per 100 person-months for each maintenance therapy. Results: 231 patients were eligible for our analysis. 169 patients received lenalidomide, 27 bortezomib and 35 combination. The most common adverse event was neutropenia and second most common is pneumonia. Neutropenia incidence was 1.1,0.7 and 0.9 per 100 person-months in lenalidomide, bortezomib and combination regimens respectively. Incidence of deep vein thrombosis, GI intolerance and peripheral neuropathy 0.1 per 100 person-months respectively was observed in lenalidomide group only. Combination maintenance had the highest total adverse event incidence rate of 5.4 per 100 person-months. Incidence of 1.7 and 3.8 per 100 person-months is observed in bortezomib and lenalidomide cohorts respectively. Conclusions: Lenalidomide and bortezomib maintenance had similar incidence of serious adverse events. A higher incidence of serious adverse events was noted in the combination lenalidomide/bortezomib regimens. Interestingly, we observed lower incidence of adverse events in all groups in CoMMpass study compared to respective clinical trials involving maintenance regimens. This may be due to under reporting of adverse events in CoMMpass study. The incidence of adverse events mentioned above should be interpreted in the context of drugs and other factors involved in the disease.

Bortezomib, Ascorbic Acid and Melphalan (BAM) Therapy for Patients (pts) with Newly Diagnosed Multiple Myeloma (MM): An Effective and Well-Tolerated Frontline Regimen.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3602-3602 ◽  
Author(s):  
James R. Berenson ◽  
Ori Yellin ◽  
Donald Woytowitz ◽  
Marshall S. Flam ◽  
Alan Cartmell ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Ascorbic Acid ◽  
Adverse Events ◽  
Progressive Disease ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Newly Diagnosed ◽  
Grade Iii

Abstract Previously, we and others have shown that bortezomib overcomes chemotherapy resistance in multiple myeloma cells. We recently published a Phase I trial that established the maximum tolerated dose (1.0 mg/m2 of bortezomib on days 1, 4, 8, and 11 with melphalan 0.1. mg/kg PO daily on days 1–4 of a 28-day cycle) for this combination and suggested its clinical activity in relapsed or refractory MM. The anti-MM activity of melphalan is dependent upon reactive oxygen species (ROS) and free glutathione (GSH) reduces intracellular ROS. Ascorbic acid (AA) reduces free GSH levels; and thus, should enhance the anti-MM activity of melphalan as our laboratory has recently demonstrated both in vitro and in vivo (Campbell et al. Brit J Haematol 2007). Therefore, we conducted a single-arm multi-center phase II study that evaluated the combination of bortezomib, ascorbic acid and melphalan (BAM) regimen in newly diagnosed pts with symptomatic myeloma. Treatment consisted of a 28-day cycle of bortezomib administered at a dose of 1.0 mg/m2 on days 1, 4, 8, and 11, and on days 1, 2, 3, and 4 oral AA at a dose of 1 g and oral melphalan 0.1 mg/kg were given. Based on preclinical studies suggesting potential inhibitory effects of AA on bortezomib’s anti-MM activity, bortezomib was administered in the morning and AA with melphalan in the evening. Pts were treated to maximum response plus two additional cycles or completed eight cycles of therapy without disease progression. These pts were eligible to be subsequently treated with bortezomib at a dose of 1.3 mg/m2 every other week until progressive disease occurred. Thirty-five pts, at a median age of 70 years (range, 50–90 years); have been enrolled in this study. To date, 27 pts are evaluable with a median survival of 12 months (range, 2 to 19+ months). Responses occurred in 17 of 27 pts (63%), including four complete responses (15%), two very good responses (7%), four partial responses (15%), and seven minimal responses (26%). Eight pts (30%) had stable disease. Thus, disease control was achieved in 25 (93%) pts. Six of the 27 pts have shown progressive disease after 2–13 months of treatment. Eleven pts experienced ≥ grade III adverse events with only one patient demonstrating a grade IV toxicity (shortness of breath). Six of these adverse events were judged not to be related to the study medications including the only grade IV event. The most common grade III adverse events included reversible neutropenia (4 events), neuropathy (2 events) and reversible thrombocytopenia (2 events). Only 11 pts had some form of increased neuropathy from baseline (Grade I (n=7), Grade II (n=2), and Grade III (n=2) with one of those pts starting with a Grade I). The peripheral neuropathy was reversible. BAM represents a steroid and IMID-free regimen with a high response rate (63%) as frontline therapy for MM pts. Importantly, this regimen was well tolerated with few significant adverse events. Treatment-related neuropathy was reported but reversible in all but one case. Thus, BAM has proven to be a promising new regimen for the first-line treatment of pts with MM.

Longer Duration of Treatment and Maintenance of Best Response with Lenalidomide and Dexamethasone Prolongs Overall Survival in Patients with Relapsed or Refractory Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3702-3702 ◽  
Author(s):  
Jesús F San Miguel ◽  
Meletios A Dimopoulos ◽  
Edward A. Stadtmauer ◽  
S. Vincent Rajkumar ◽  
David Siegel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Events ◽  
Disease Progression ◽  
Phase Iii ◽  
Duration Of Treatment ◽  
Early Discontinuation ◽  
Landmark Analysis ◽  
Best Response ◽  
The Impact

Abstract Introduction: Multiple myeloma (MM) accounts for about 20% of deaths from hematological cancers and remains incurable despite conventional and high-dose chemotherapy. Two phase III trials in patients with relapsed or refractory MM (MM-009 and MM-010) showed that lenalidomide combined with dexamethasone resulted in significantly improved response rates and significantly prolonged median time to progression (TTP) and overall survival (OS) compared with dexamethasone alone. This current sub-analysis of lenalidomide plus dexamethasone therapy assessed whether there was a survival benefit in maintaining patients on therapy after achieving their best response and what the impact of early discontinuation on TTP and OS was. Methods: Of the 353 patients from MM-009 and MM-010 treated with lenalidomide plus dexamethasone, 32 did not respond. Of the remaining 321 responding patients, 214 had a partial response (PR) or better and 107 patients had stable disease (SD). In this post-hoc sub-analysis, we first assessed the outcome of continuing treatment for ≤10 months vs. >10 months in all 321 patients who achieved SD or better, after they achieved their best response. In this landmark analysis, OS was measured from the time of achieving best response to death from any cause or to last contact. In a second analysis, we assessed the impact of early discontinuation due to adverse events or withdrawn consent on OS and TTP in all patients who achieved SD or better. Therefore, we excluded patients who discontinued treatment due to disease progression, death, or lack of efficacy. Patients who achieved SD or better and who continued on therapy were compared with those who discontinued. OS and TTP were assessed from time of randomization. Results: In the landmark analysis, of the 321 responding patients (≥PR, n=214; SD, n=107), 223 patients received treatment for ≤10 months after achieving their best response and 98 patients for >10 months after achieving their best response. Patients who continued therapy for >10 months after achieving their first best response had significantly longer OS vs. those who received therapy for ≤10 months (not reached vs. 23.4 months; p<0.0001). At 24 months after achieving their best response, significantly more patients were alive if they continued therapy >10 months vs. ≤10 months (93.8% vs. 48.4%, p<0.0001). In the second analysis, in order to evaluate the impact of discontinuation in patients achieving SD or better, we excluded 134 patients due to disease progression, death, or lack of efficacy. Of the remaining 187 responding patients, 72 discontinued treatment for AE (n=42) or withdrew consent (n=30), while the remaining 115 patients continued treatment. Median OS and TTP were significantly longer for patients who continued vs. those who discontinued treatment (median OS: not reached vs. 29.5 months, p<0.0001; median TTP: not reached vs. 13.6 months, p<0.0001). Conclusions: In patients achieving SD or better, prolonged duration of treatment was associated with significantly longer OS and TTP. In contrast, early discontinuation of treatment led to reduced OS and TTP. Therefore, efforts should be made to manage adverse events while maintaining patients on therapy. Furthermore, maintaining treatment with lenalidomide and dexamethasone after achieving the optimal response ensures a significant improvement in OS for patients with relapsed or refractory MM.

Clinical Efficacy of Pegylated Liposomal Doxorubicin, Vincristine and Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5212-5212
Author(s):  
Wen Wu ◽  
Xiaodong Gao ◽  
Lan Xu ◽  
Hua Yan ◽  
Zhixiang Shen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Partial Response ◽  
Adverse Events ◽  
Median Time ◽  
Liposomal Doxorubicin ◽  
Gastrointestinal Symptoms ◽  
Pegylated Liposomal Doxorubicin ◽  
High Response Rate ◽  
Newly Diagnosed

Abstract Object: To investigate the short-term and long-term efficacy and toxicity of pegylated liposomal doxorubicin, vincristine and dexamethasone (DVD) in patients with newly diagnosed multiple myeloma (MM). Methods: Twenty-five patients (13 males, 12 females, median age 55 years) with newly diagnosed multiple myeloma were treated with pegylated liposomal doxorubicin 40 mg/m2 and vincristine 2 mg intravenously on day 1 plus dexamethasone 40 mg intravenously or orally on days 1–4 (DVD) for median 4.5 (2–8) cycles. Treatment was repeated every 4 weeks. Response was evaluated according to the International Uniform Response Criteria for Multiple Myeloma (2006) before initiation of each course. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Results: After 4.5 (2–8) courses of the median cycles, clinical response was observed in 20 patients (80%), including complete response in 4 (16%), very good partial response in 3 (12%), partial response in 10 (40%), minimal response in 3 (12%) and stable disease in 2 (8%). The median time to initial response was 1.2 months and the median time to best response was 4 months. After 25 (2–50) months of median follow-up, the median progression-free survival was 20 months, while the median overall survival has not yet been reached. The overall survival rate was 72% (18/25). The most common adverse events were gastrointestinal symptoms (nausea and vomiting in 10, constipation in 9 patients), neutropenia (7 patients), anemia (6 patients) and thrombocytopenia (4 patients). DVD was associated with more hand-foot syndrome (4 patients) and mucitis (2 patients). Conclusions: DVD scheme is an effective therapy with a high response rate and manageable toxicities for patients with newly diagnosed multiple myeloma.

Combination therapy based on bortezomib for 102 patients with newly-diagnosed multiple myeloma: a Chinese experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5116-5116
Author(s):  
Jingsong He ◽  
Li Yang ◽  
Xiaoyan Han ◽  
Gaofeng Zheng ◽  
Xiaojian Meng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Peripheral Neuropathy ◽  
Combination Therapy ◽  
Adverse Events ◽  
Chinese Population ◽  
Median Overall Survival ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Significant Difference

Abstract Abstract 5116 Multiple myeloma (MM) is a malignant neoplasm of plasma. The rates of complete remission (CR) or very good partial remission (VGPR) for patients received conventional chemotherapy are still low with median overall survival about 3 years. Here we report our results with combination therapy based on bortezomib in the Chinese population and investigat the efficacy and safety of Bortezomib-based therapies in previously untreated MM patients. Metohds: Between 1st Feb. 2006 and 31st Dec. 2010, 102 consecutive newly-diagnosed patients with symptomatic MM were treated with combination therapies based on bortezomib. Sixty-four patients were male and 38 were female. Median age was 59 years (range 31–86 years). Forty-two patients were stage 3 according to the International Staging System, 36 patients were stage 2 and 24 patients were stage 1. The combinations included dexamethasone (BD group ), dexamethasone plus subsequent thalidomide (BDT group ) and dexamethasone plus cyclophosphamide (BDC group ) or epirubicin (BDA group ) based on bortezomib. Thirty-five patients were in BDT group, 19 in BD group, 32 in BDC group and 16 in BDA. All patients received a median of three cycles of therapy (range 1–5 ). The IMWG criteria was used for response evaluation and toxicities were evluated according to the NCI Common Toxicity Criteria version 3. Results: The efficacy of the triplet combination therapy based on bortezomib including BDT, BCD and BAD were better than BD group, with response rate greater than or equal to partial remission(≥PR) 85.7%, 90.6%, 93.7% and 68.4%, respectively. The efficacy of BDA and BDC group were significantly superior to BD group (P=0.048,0.050). Bortezomib in combination with chemotherapy was highly effective as treatment for symptomatic multiple myeloma, even only after one cycle. The efficacy for patients received one cycle of BDT, BD, BCD and BAD was 65.7%, 42.1%, 65.6% and 62.5%, respectively. Patients treated with BD had suboptimal responses to those received BDT, BCD and BAD treatment and one cycle of BCD was superior to one cycle of BD (P=0.019).The median follow-up time was 17m (1–60m), including 31m (1–60m) for 35 patients in BDT group and 16m (2–29m) for the remaining 67 patients. The median progression-free survival (PFS ) of BDT group was 15m (9.8–20.2m ) while BD group was 12m (8.1–15.8m), BCD group was 13m (5.9–20.1m ), and BAD group was 12m (7.8–16.2m ), without significant difference. The median overall survival (OS ) of BDT group was 35m (13.2–56.8m ) while BD, BCD and BAD groups was not reached yet. There was no significant difference in OS among groups, but BCD and BAD were superior to BD group (P=0.104, 0.142 ). The frequent treatment-emergent adverse events includes hematologic adverse events such as neutropenia, anemia, thrombocytopenia and the non-hematologic adverse events like fatigue, infection, constipation, diarrhea, pleural effusion and ascites, herpes zoster and peripheral neuropathy. Patients treated with BDT were more likely to show peripheral neuropathy than those treated with BD, BCD and BAD (91.4% vs 73.6%, 68.7%, 74.9% ), but there is no statistical significant difference (P = 0.131), Grade 2 or 3 peripheral neuropathy was occurred in 45.7% of BDT group significantly higher than BD, BCD and BAD groups. (21.0%, 15.7% and 18.7%, P = 0.028 ). Other related adverse events in all the groups had no significant difference. Routine anticoagulation or anti-thrombsis were not used. Only 1 patient suffered from DVT/PE but did well with treatment. Conclusions: Our preliminary experience in Chinese patients indicated that combination chemotherapy based on bortezomib is highly effective in newly-diagnosed multiple myeloma and BDC, BDA or BDT regimens may be more superior to BD in Chinese population. There were relative lower rates of DVT/PE in the Chinese patients with MM received combination chemotherapy based on bortezomib. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 36 ◽  
Author(s):  
Antonio Facciorusso ◽  
Mohamed A. Abd El Aziz ◽  
Rodolfo Sacco
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Adverse Events ◽  
Therapeutic Option ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sensitivity Analyses ◽  
Free Survival

Regorafenib showed promising results as a second-line agent after sorafenib failure in hepatocellular carcinoma patients. The aim of this meta-analysis was to evaluate the efficacy and safety of regorafenib in hepatocarcinoma patients. A computerized bibliographic search was performed on the main databases. The primary outcome was overall survival. Secondary outcomes were progression-free survival, tumor response, and the adverse events rate. Outcomes were pooled through a random-effects model and summary estimates were expressed in terms of median and 95% confidence interval or rates, as appropriate. One randomized-controlled trial and seven non-randomized studies with 809 patients were included. The great majority of recruited patients were in Child-Pugh A and ECOG 0 stage. Median overall survival was 11.08 months (9.46–12.71) and sensitivity analyses confirmed this finding, with a median survival ranging from 10.2 to 13.8 months. Duration of regorafenib therapy was 3.58 months, whereas median progression-free survival was 3.24 months (2.68–3.86). The pooled objective response rate was 10.1% (7.8–12.5%) while the disease control rate was 65.5% (61.3–69.7%) with no evidence of heterogeneity (I2 = 0%; Diarrhea, fatigue, and hand-foot skin reaction were the most frequent adverse events. The current meta-analysis shows that regorafenib represents a valuable and relatively safe therapeutic option in intermediate/advanced hepatocellular carcinomapatients who progress on sorafenib.

scholarly journals Indirect Comparison Using Individual Patient Level Data Comparing Efficacy and Safety of a Daratumumab Monotherapy Vs. EU Approved Comparator Therapies in Patients with Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3541-3541 ◽  
Author(s):  
Irina Demmer ◽  
Susanne Huschens ◽  
Dietrich Potthoff ◽  
Jörg Tomeczkowski ◽  
Christian Englisch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Sensitivity Analyses ◽  
Control Group ◽  
Efficacy And Safety ◽  
Advisory Committees ◽  
Refractory Multiple Myeloma

Abstract Introduction. Efficacy and safety of daratumumab monotherapy (DARA mono) in relapsed/refractory multiple myeloma (rrMM) has been shown in the single-arm phase I/II trial GEN501 and the single-arm phase II trial SIRIUS (1, 2). Since then, several indirect treatment comparisons of DARA mono versus comparator therapies have been published showing consistent results with an overall survival benefit for DARA mono (3, 4, 5, 6). This analysis compares efficacy and for the first time also safety of DARA mono data versus an international historic control group, adjusting for differences in patient populations based on individual patient level data (IPD). Methods. IPD from the SIRIUS trial and from the International Myeloma Foundation (IMF)-cohort (7), a retrospective, multicenter cohort, were compared using a multivariate Cox proportional hazards model, on the endpoints of efficacy (overall survival (OS)) and safety (discontinuation due to adverse events (DISCONAE)). The IMF-cohort included patients with rrMM who received at least three prior lines of therapy, were refractory to both an immunomodulator (IMiD) and a proteasome inhibitor (PI), and were exposed to an alkylating agent. An inclusion criterion for the historic control group in this analysis was treatment with EU approved regimens. Baseline covariates adjusted for in the regression model included age, gender, prior lines of therapy, albumin, beta-2 microglobulin, prior exposure to pomalidomide and carfilzomib, and PI/IMiD refractory status. Several sensitivity analyses were run, including multiple imputation of missing values. Results. Data from 106 patients treated with DARA mono (16 mg/kg) were available from SIRIUS; 258 patients from the IMF chart review fulfilled the inclusion criteria; most frequent treatment regimens contained pomalidomide plus dexamethasone (PomDex) (n=172), bortezomib (n=31), carfilzomib (n=21), cyclophosphamide (n=14) and lenalidomide (n=9). The adjusted HR for OS was 0.41 [0.25, 0.69], p<0.001, and 0.23 [0.05, 1.00], p=0.050 for DISCONAE, in favor of daratumumab. Results were consistent across a range of sensitivity analyses and were similar when restricting the comparison to DARA vs. PomDex, with HR=0.35 [0.19, 0.64], p<0.001 for OS and 0.20 [0.03, 1.54], p=0.123 for DISCONAE. Conclusions. This comparison using real-world data of rrMM patients suggests improved efficacy and safety for DARA mono compared to approved therapy regimens used in clinical practice, including PomDex. References. Lokhorst, H. M., Plesner, T., Laubach, J. P., Nahi, H., Gimsing, P., Hansson, M., et al. Targeting CD38 With Daratumumab Monotherapy in Multiple Myeloma. The New England Journal of Medicine. 2015. Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, et al. Daratumumab Monotherapy in Patients with Treatment-Refractory Multiple Myeloma (SIRIUS): An Open-Label, Randomised, Phase 2 Trial. The Lancet. 2016. Usmani S, Ahmadi T, Ng Y, Lam A, Desai A, Potluri R, Mehra M. Analysis of Real-World Data on Overall Survival in Multiple Myeloma Patients With ≥3 Prior Lines of Therapy Including a Proteasome Inhibitor (PI) and an Immunomodulatory Drug (IMiD), or Double Refractory to a PI and an IMiD. The Oncologist. 2016. Van Sanden S, Ito T, Diels J, Vogel M, Belch A, Oriol A. Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison. The Oncologist. 2017. Usmani SZ, Diels J, Ito T, Mehra M, Khan I, Lam A. Daratumumab monotherapy compared with real-world historical control data in heavily pretreated patients with highly refractory multiple myeloma: An adjusted treatment comparison. American Journal of Heamtology. 2017. Jelínek T, Maisnar V, Pour L, Špička I, Minařík J, Gregora E, et al. Adjusted comparison of daratumumab monotherapy versus real-world historical control data from the Czech Republic in heavily pretreated and highly refractory multiple myeloma patients. Current Medical Research an Opinion. 2017. Kumar SK, Dimopoulos MA, Kastritis E, Terpos E, Nahi H, Goldschmidt H, et al. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia. 2017. Disclosures Demmer: Janssen: Employment. Huschens:Janssen: Employment. Potthoff:Janssen: Employment. Tomeczkowski:Janssen: Employment. Englisch:Janssen: Employment. Thilakarathne:Janssen: Employment. Diels:Janssen: Employment. Kumar:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: 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, Research Funding. Durie:Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Janssen: Consultancy. Eisele:Janssen: Employment.

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