scholarly journals Comparative Effectiveness of Treatment Strategies For Multiple Myeloma in Elderly Patients: A Network Meta-Analysis

2016 ◽  
Vol 19 (7) ◽  
pp. A710 ◽  
Author(s):  
M Buchberger ◽  
U Rochau ◽  
D Vukicevic ◽  
W Willenbacher ◽  
A Chaimani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Comparative Effectiveness ◽  
Meta Analysis ◽  
Treatment Strategies

scholarly journals Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis

BMJ ◽  
2014 ◽  
Vol 348 (may13 3) ◽  
pp. g3009-g3009 ◽  
Author(s):  
R. J. B. Loymans ◽  
A. Gemperli ◽  
J. Cohen ◽  
S. M. Rubinstein ◽  
P. J. Sterk ◽  
...  
Keyword(s):  
Drug Treatment ◽  
Comparative Effectiveness ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Asthma Exacerbations

Melphalan and Prednisone (MP) Versus Melphalan, Prednisone and Thalidomide (MPT) as Initial Therapy for Previously Untreated Elderly and/or Transplant Ineligible Patients with Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 615-615 ◽  
Author(s):  
Prashant Kapoor ◽  
S. Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
David Dingli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Randomized Controlled Trials ◽  
Research Funding ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
The Impact

Abstract Abstract 615 Background: Trials comparing efficacy of standard melphalan prednisone (MP) therapy with MP plus thalidomide (T) in the transplant ineligible, elderly patients with multiple myeloma have provided conflicting evidence. While there is greater agreement with regard to superior response rates (RR) with the addition of T to MP in elderly patients, the impact on progression free survival (PFS) and overall survival (OS) is less clear with some trials showing an improvement in PFS and/or OS with MPT and others demonstrating no difference in outcomes. We performed a systematic review to integrate the existing outcome data related to the efficacy of MP vs. MPT using a meta-analytic approach. Methods: A comprehensive search of electronic database through July 31st, 2009 was performed for publications, abstracts and presentations to identify randomized controlled trials (RCTs) comparing MP with MPT. A meta-analysis was performed by pooling results on clinical endpoints of RR, PFS and OS reported in all the identified RCTs under a random effects model. We did not have access to individual patient data from these trials. Results: Overall, five prospective RCTs (3 published articles and 2 abstracts) comparing MP with MPT regimen and comprising a total of 1571 patients were identified. For the endpoints of OS and PFS, data were extractable only from 4 RCTs (abstract by Gulbrandsen et al. was excluded). The Bregg and Egger funnel plot for OS demonstrated a symmetric distribution (P = 0.6) indicating no significant publication bias. The test of heterogeneity among all RCTs was statistically significant in the estimate of RR (tau2=0.21; chi2=16.33; p=0.003 (df=4); I2 = 75.5%), but not significant for the estimates of PFS (tau2=0.01; chi2=4.61; p=0.2 (df=3); I2 = 34.9%), and OS (tau2=0.02; chi2=5.53; p=0.14 (df=3); I2 = 45.8%). As expected, the pooled odds ratio of responding to treatment with MP versus MPT was 0.307 (P<0.001) indicating that MP was worse than MPT in achieving at least a partial response. The pooled hazard ratios (HR) for PFS and OS were 1.59 (p<0.001) and 1.34 (p=0.006), respectively (see table for forest plots) in favor of MPT. Conclusion: Our meta-analysis implies that in previously untreated, transplant ineligible elderly patients with multiple myeloma, the addition of thalidomide to melphalan-prednisone demonstrates improved RR, PFS and OS compared with the use of melphalan-prednisone alone. Although the results from a comprehensive individual patient data pooled analysis would give a more precise estimate, our analysis suggests that MPT is superior to MP in terms of response and survival. Disclosures: Dispenzieri: Celgene: Research Funding. Gertz:Celgene: Honoraria. Kumar:celgene, genzyme, millennium, novartis, bayer: Research Funding; genzyme: Membership on an entity's Board of Directors or advisory committees.

Comparative Effectiveness of Lenalidomide Plus Dexamethasone for the Treatment of Refractory/Relapsed Multiple Myeloma: A Systematic Review and Mixed Treatment Comparison

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4076-4076
Author(s):  
Sallie Stradwick ◽  
Nick Freemantle ◽  
John Snowden ◽  
Felipe Rodrigues ◽  
Nic Brereton
Keyword(s):  
Multiple Myeloma ◽  
Combination Therapy ◽  
Confidence Intervals ◽  
Random Effects ◽  
Comparative Effectiveness ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Treatment Comparison ◽  
Mixed Treatment ◽  
Secondary Outcomes

Abstract Abstract 4076 OBJECTIVES: To evaluate the comparative effectiveness of lenalidomide (25 mg) plus dexamethasone (40 mg) (LEN/dex) for the treatment of relapsed/refractory multiple myeloma (RRMM) compared to thalidomide and bendamustine. Primary outcome of interest was time to progression (TTP). Secondary outcomes of interest were overall response rates (ORR) and overall survival (OS). METHODS: A comprehensive systematic literature review was conducted to identify any randomised controlled trials (RCTs) investigating the clinical efficacy of specified therapies for the treatment of RRMM. Specified therapies included lenalidomide, thalidomide and bendamustine. Of these therapies, only LEN/dex combination therapy is approved in RRMM but bendamustine and thalidomide (monotherapy or in combination with dexamethasone) have also shown activity in the treatment of myeloma. Electronic databases were searched from March 2002 to 2012 (language unrestricted. Randomized clinical trials were independently evaluated against predetermined criteria for inclusion and determined to be eligible for the meta-analysis prior to any outcome assessment. Fixed effects and random effects mixed-treatment comparisons (MTC) were carried out, adopting the methods described by Lu and Ades1. MTCs estimate the comparative effectiveness of multiple treatments using an evidence base of trials that individually do not compare all treatment options. Results for TTP were reported as hazard ratios (HR) and 95% confidence intervals and an associated probability of best treatment. Results for binary variables (ORR, OS) were reported as odds ratios (OR) and 95% confidence intervals. RESULTS: Sixteen original RCTs met the initial inclusion criteria; twelve (N = 3,590), nine (N = 3,350) and six (N = 2,295) of which were able to be connected to form a network of evidence which provided the heterogeneous trial base for MTC analysis of ORR, OS, and TTP comparison, respectively. Two trials directly investigated the efficacy of LEN/dex (N = 353) and three trials assessed the efficacy of thalidomide monotherapy (N = 785). No RCTs were identified that investigated the efficacy of bendamustine or thalidomide/dexamethasone combination therapy in RRMM. There were too few studies (investigating treatment arms of interest) relative to the number of trials in the network to formally estimate or test for heterogeneity. Therefore a fixed effects network meta-analysis was used instead of a random effects network meta-analysis. Comparability of trial populations was assessed and discussed in detail since these could not be adjusted for in the statistical model. Age, sex, baseline disease characteristics, time since diagnosis and medical history were similar between study populations. TTP analysis was statistically significant and favoured LEN/dex over thalidomide monotherapy: HR = 2.34 [1.31, 4.17]. The associated probability of LEN/dex being the best treatment within the evidence network is 97.9%. Secondary outcomes analysis were also statistically significant in favour of LEN/dex over thalidomide monotherapy (ORR: OR = 10.48 [4.75, 22.81]; OS: OR = 1.43 [1.12, 1.84]). CONCLUSIONS: Results demonstrated statistically significant superiority of lenalidomide plus dexamethasone therapy versus thalidomide monotherapy for the treatment of RRMM. No analyses were possible versus bendamustine or thalidomide/dexamethasone combination therapy due to the lack of RCTs investigating the efficacy of these therapeutic regimens in RRMM. Disclosures: Stradwick: Celgene International: Consultancy. Freemantle:BresMed: Consultancy. Off Label Use: Thalidomide monotherapy activity in the treatment of myeloma. Brereton:Celgene International: Consultancy.

Treatment Strategies in Elderly Patients with Multiple Myeloma

Drugs & Aging ◽  
2007 ◽  
Vol 24 (10) ◽  
pp. 829-850 ◽  
Author(s):  
Hang Quach ◽  
H Miles Prince ◽  
Linda Mileshkin
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Treatment Strategies

Bortezomib Once Weekly Is Well Tolerated as Maintenance Therapy after Less Than a Complete Response to High-Dose Melphalan in Patients with Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5099-5099 ◽  
Author(s):  
Stefan Knop ◽  
Holger Hebart ◽  
Volker Kunzmann ◽  
Ralf Angermund ◽  
Hermann Einsele
Keyword(s):  
Multiple Myeloma ◽  
Interferon Alpha ◽  
Residual Disease ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Rest Period ◽  
Salvage Treatment ◽  
High Dose ◽  
Significant Prolongation ◽  
High Dose Melphalan

Abstract Background: Despite intensive treatment strategies in multiple myeloma (MM) consisting of one or two cycles of high-dose melphalan (HD-Mel) with autologous stem cell support only a minority of patients (pts) achieves molecular complete remission leading to an event free survival (EFS) of eight to ten years. The median EFS for all patients following HD-Mel, however, is no more than 30 to 35 months. Several agents have been evaluated as a part of maintenance strategies in order to eradicate minimal residual disease and thus extending the period until salvage treatment is required. Interferon alpha, that has been most widely used in this setting showed a significant prolongation of EFS and a trend to better overall survival in a large meta-analysis. Bortezomib (VELCADE® [Vel]), a proteasome inhibitor, has substantial anti-myeloma activity in relapsed and refractory disease and was shown to induce exceptional response rates, including consistently high CR rates in up-front treatment. Patients and methods: We decided to set up a phase II trial in patients up to 70 years with less than CR (SD, PR, or VGPR) after one or two cycles of HD-Mel using a less dose-intense schedule than the standard protocol for monotherapy. The first eleven pts were to receive four cycles of Vel 1.0 mg/m2 once weekly for four weeks followed by a two-week rest period. Since no dose limiting toxicity occurred, the dose was increased as per protocol to 1.3 mg/m2 for the subsequent pts. Results: Up to now, 20 subjects were included with a median age of 60.5 (range, 46 – 69) years, 3 of whom had previously received single, and 17 tandem HD-Mel. Two cases of moderately severe herpes zoster prompted us to generally administer acyclovir prophylaxis throughout the treatment. Five pts experienced symptoms of peripheral neuropathy all of which were of grade I. WBC nadir occurred during cycles 2 and 3 with a median of 3.7 × 109/l while median PLT and HB values did not decline below normal values. Three patients progressed while on the study and received salvage treatment while all other patients enrolled completed all four scheduled cycles of treatment. To date, two patients showed improvement of response by conversion of VGPR into CR with confirmed negative immunofixation. Conclusion: We are currently continuing patient accrual on the once-weekly 1.3 mg/m2 schedule since treatment is considered to be safe. Data on the efficacy (i.e. median EFS, OS as compared to historic controls on interferon alpha), however, will require significantly longer follow up.

scholarly journals Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN)

Blood ◽  
2011 ◽  
Vol 118 (17) ◽  
pp. 4519-4529 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Heinz Ludwig ◽  
Meletios A. Dimopoulos ◽  
Joan Bladé ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Standard Treatment ◽  
Autologous Transplantation ◽  
Treatment Strategies ◽  
Dose Intensity ◽  
Newly Diagnosed ◽  
Improved Outcomes ◽  
Drug Doses ◽  
Vulnerable Elderly

Abstract Most patients with newly diagnosed multiple myeloma (MM) are aged > 65 years with 30% aged > 75 years. Many elderly patients are also vulnerable because of comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time because of an aging population. Most elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more susceptible to side effects and are often unable to tolerate full drug doses. For these patients, lower-dose-intensity regimens improve the safety profile and thus optimize treatment outcome. Further research into the best treatment strategies for vulnerable elderly patients is urgently needed. Appropriate screening for vulnerability and an assessment of cardiac, pulmonary, renal, hepatic, and neurologic functions, as well as age > 75 years, at the start of therapy allows treatment strategies to be individualized and drug doses to be tailored to improve tolerability and optimize efficacy. Similarly, occurrence of serious nonhematologic adverse events during treatment should be carefully taken into account to adjust doses and optimize outcomes.

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