Differences in safety profiles of newly approved medications for multiple myeloma in real-world settings versus randomized controlled trials

2020 ◽  
pp. 107815522094193
Author(s):  
Eric P Borrelli ◽  
Conor G McGladrigan
Keyword(s):  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Adverse Drug Reactions ◽  
Malignant Neoplasm ◽  
Controlled Trials ◽  
Site Reaction ◽  
Drug Reactions ◽  
Infusion Site ◽  
Randomized Controlled ◽  
Fda Approval

Background Four new agents (elotuzumab, ixazomib, panobinostat, and daratumumab) were approved by the US Food and Drug Administration (FDA) in 2015 for the treatment of multiple myeloma. Our objective was to compare the safety profiles of these new medications in real-world settings and their randomized controlled trial(s). Material and methods An analysis was conducted of the FDA Adverse Event Reporting System (FAERS) for each drug consisting of the quarter that the drug received its FDA approval and the eight subsequent quarters. Reporting odds ratios and corresponding 95% confidence intervals were then calculated for each drug for each of the 10 most frequent adverse drug reactions. The randomized controlled trials that led to initial FDA approval for these medications were subsequently reviewed to assess the 10 most frequently reported adverse drug reactions in these trials. Results There were only two adverse drug reactions in the top 10 of both FAERS and its randomized controlled trials for elotuzumab (anaemia, diarrhoea) and for daratumumab (cough, back pain), five for ixazomib (diarrhoea, constipation, fatigue, nausea, peripheral neuropathy), and four panobinostat (diarrhoea, fatigue, nausea, constipation). Ixazomib had two adverse drug reactions with a significant reporting odds ratios greater than a 10-fold increased risk (plasma cell myeloma, peripheral neuropathy); elotuzumab had three adverse drug reactions (infusion site reaction, malignant neoplasm progression, deep vein thrombosis); daratumumab had three adverse drug reactions (infusion site reaction, bronchospasm, chills), while panobinostat had four (malignant neoplasm progression, decreased platelet count, diarrhoea, increased blood creatinine). Conclusion This analysis helps to highlight the importance of conducting postmarketing pharmacovigilance studies to better understand the potential adverse reactions of these medications.

Use of Endpoints in Multiple Myeloma Randomized Controlled Trials over the Last Fifteen Years: A Systematic Review

2021 ◽  
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Kelly Koehn ◽  
Al‐Ola Abdallah ◽  
Douglas Sborov ◽  
S. Vincent Rajkumar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Controlled Trials ◽  
Randomized Controlled

Multiple Myeloma Patients Ineligible for Randomized Controlled Trials Have Poorer Outcomes Irrespective of Treatment

2018 ◽  
Vol 18 (9) ◽  
pp. e363-e364 ◽  
Author(s):  
Mary-Kate Malecek ◽  
Mark Fiala ◽  
Mark Schroeder ◽  
James Dukeman ◽  
Armin Ghobadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Controlled Trials ◽  
Randomized Controlled

Thromboprophylaxis In Multiple Myeloma Patients Undergoing Immunomodulatory Therapy with Thalidomide and Lenalidomide: A Systematic Review and Meta-Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1090-1090
Author(s):  
Marc Carrier ◽  
Gregoire Le Gal ◽  
Jason Tay ◽  
Cynthia M. Wu ◽  
Agnes Y. Lee
Keyword(s):  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Newly Diagnosed ◽  
Bleeding Events ◽  
Randomized Controlled ◽  
Literature Search Strategy ◽  
Previously Treated ◽  
Data Source

Abstract Abstract 1090 Background: The incidence of venous thromboembolism (VTE) in patients with multiple myeloma (MM) is high in patients treated with thalidomide (T)- and lenalidomide (L)-based regimens containing dexamethasone (D) and/or cytotoxic chemotherapy (C). Consensus guidelines recommend routine thromboprophylaxis but reliable data from randomized controlled trials are lacking. Recent observational studies have suggested that thromboprophylaxis might be efficacious in decreasing the risk of VTE in this population. Purpose: To determine the absolute rates of VTE with and without different thromboprophylactic agents (ASA, warfarin, low-molecular-weight-heparin [LMWH]) in patients with newly diagnosed or previously treated MM receiving T- or L-based regimens. Data Source: A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews of published studies up to Jan 2010. Results: A total of 66 studies were included in the analyses. Of these, 61 (4264 patients) and 5 (1119 patients) assessed T- and L-based regimens, respectively. Thalidomide-based regimens The rates of VTE (per 100 patient-cycles) in patients with newly diagnosed MM treated with T-based regimens: The rates of VTE (per 100 patient-months) in patients with previously treated MM managed with T-based regimens: Lenalidomide-based regimens The rates of VTE (per 100 patient-cycles) in patients with newly diagnosed MM treated with L-based regimens: The rate VTE (per 100 patient-months) in patients with previously treated MM managed with L-based regimens: None of the studies reported major bleeding events. Limitations: The definition for VTE varied across studies. Most studies did not outline the diagnostic criteria for VTE. Data are not available (NA) for all prophylaxis regimens. Conclusion: Patients with newly diagnosed or previously treated MM receiving T- or L-based regimens are at high risk of VTE. It is uncertain whether thromboprophylaxis provides a clear benefit, especially in those receiving L-based therapy or have previously treated disease. Randomized controlled trials are needed to address this important clinical need. Disclosures: Lee: Eisai: Research Funding; Sanofi Aventis: Consultancy, Honoraria; Leo Pharma: Consultancy; Pfizer: Consultancy, Honoraria; Bayer: Honoraria; Boehringer Ingelheim: Consultancy, Honoraria, Speakers Bureau.

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.

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