scholarly journals Safety Profile of Ixazomib in Patients with Relapsed/Refractory Multiple Myeloma in Japan: An All-case Post-marketing Surveillance

2022 ◽  
Author(s):  
Yoshihide Kakimoto ◽  
Miyako Hoshino ◽  
Mikiko Hashimoto ◽  
Masaya Hiraizumi ◽  
Kohei Shimizu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Safety Profile ◽  
Refractory Multiple Myeloma ◽  
Post Marketing Surveillance ◽  
Post Marketing

scholarly journals The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110196
Author(s):  
Albert Oriol ◽  
Laura Abril ◽  
Anna Torrent ◽  
Gladys Ibarra ◽  
Josep-Maria Ribera
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Safety Profile ◽  
Proteasome Inhibitors ◽  
Clinical Development ◽  
Phase Iii ◽  
Acceptable Safety Profile ◽  
Refractory Multiple Myeloma ◽  
High Risk Patients ◽  
Risk Patients

The development of several treatment options over the last 2 decades has led to a notable improvement in the survival of patients with multiple myeloma. Despite these advances, the disease remains incurable for most patients. Moreover, standard combinations of alkylating agents, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies targeting CD38 and corticoids are exhausted relatively fast in a proportion of high-risk patients. Such high-risk patients account for over 20% of cases and currently represent a major unmet medical need. The challenge of drug resistance requires the development of highly active new agents with a radically different mechanism of action. Several immunotherapeutic modalities, including antibody–drug conjugates and T-cell engagers, appear to be promising choices for patients who develop resistance to standard combinations. Chimeric antigen-receptor-modified T cells (CAR-Ts) targeting B-cell maturation antigen have demonstrated encouraging efficacy and an acceptable safety profile compared with alternative options. Multiple CAR-Ts are in early stages of clinical development, but the first phase III trials with CAR-Ts are ongoing for two of them. After the recent publication of the results of a phase II trial confirming a notable efficacy and acceptable safety profile, idecabtagene vicleucel is the first CAR-T to gain regulatory US Food and Drug Administration approval to treat refractory multiple myeloma patients who have already been exposed to antibodies against CD38, proteasome inhibitors, and immunomodulatory agents and who are refractory to the last therapy. Here, we will discuss the preclinical and clinical development of idecabtagene vicleucel and its future role in the changing treatment landscape of relapsed and refractory multiple myeloma.

scholarly journals Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials

2018 ◽  
Vol 2 (13) ◽  
pp. 1633-1644 ◽  
Author(s):  
Ajai Chari ◽  
A. Keith Stewart ◽  
Stuart D. Russell ◽  
Philippe Moreau ◽  
Joerg Herrmann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Safety Profile ◽  
Cardiovascular Safety ◽  
Refractory Multiple Myeloma

scholarly journals Melflufen: A Peptide–Drug Conjugate for the Treatment of Multiple Myeloma

2020 ◽  
Vol 9 (10) ◽  
pp. 3120
Author(s):  
María-Victoria Mateos ◽  
Joan Bladé ◽  
Sara Bringhen ◽  
Enrique M Ocio ◽  
Yvonne Efebera ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Cells ◽  
Safety Profile ◽  
Alkylating Agents ◽  
Phase Iii ◽  
Clinical Activity ◽  
Peptide Drug ◽  
Second Line ◽  
Refractory Multiple Myeloma ◽  
Drug Conjugate

Despite the availability of new therapies that have led to improved outcomes for patients with multiple myeloma, most patients will eventually relapse. With triplet and even quadruplet combination therapies becoming standard in the first and second line, many patients will have few treatment options after second-line treatment. Melflufen (melphalan flufenamide) is a first-in-class peptide–drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Once inside the tumor cells, melflufen is hydrolyzed by peptidases to release alkylator molecules, which become entrapped. Melflufen showed anti-myeloma activity in myeloma cells that were resistant to bortezomib and the alkylator melphalan. In early phase studies (O-12-M1 and HORIZON [OP-106]), melflufen plus dexamethasone has demonstrated encouraging clinical activity and a manageable safety profile in heavily pretreated patients with relapsed/refractory multiple myeloma, including those with triple-class refractory disease and extramedullary disease. The Phase III OCEAN study (OP-104) is further evaluating melflufen plus dexamethasone in patients with relapsed/refractory multiple myeloma. The safety profile of melflufen is characterized primarily by clinically manageable hematologic adverse events. Melflufen, with its novel mechanism of action, has the potential to provide clinically meaningful benefits to patients with relapsed/refractory multiple myeloma, including those with high unmet needs.

scholarly journals Adverse events following immunisation with a meningococcal serogroup B vaccine: report from post-marketing surveillance, Germany, 2013 to 2016

2018 ◽  
Vol 23 (17) ◽  
Author(s):  
Dirk Mentzer ◽  
Doris Oberle ◽  
Brigitte Keller-Stanislawski
Keyword(s):  
Adverse Events ◽  
Safety Profile ◽  
Subcutaneous Tissue ◽  
Neurological Diseases ◽  
Proportional Reporting Ratio ◽  
Individual Case ◽  
European Medicines Agency ◽  
System Organ Class ◽  
Post Marketing Surveillance ◽  
Post Marketing

Background and aim In January 2013, a novel vaccine against Neisseria meningitidis serogroup B, the multicomponent meningococcal serogroup B vaccine (4CMenB), was approved by the European Medicines Agency. We aimed to evaluate the safety profile of this vaccine. Methods: All adverse events following immunisation (AEFI) reported from Germany since the vaccine’s launch in Germany in November 2013 through December 2016 were reviewed and analysed. Results: Through December 2016, a total of 664 individual case safety reports (ICSR) notifying 1,960 AEFI were received. A majority of vaccinees for whom AEFI were reported were children 2 to 11 years of age (n = 280; 42.2%) followed by infants and toddlers aged 28 days to 23 months (n = 170; 25.6%). General disorders and administration site conditions was the System Organ Class (SOC) with the majority of AEFI (n = 977; 49.8%), followed by nervous system disorders (n = 249; 12.7%), and skin and subcutaneous tissue disorders (n = 191; 9.7%). Screening of patient records for immune-mediated and neurological diseases did not raise any safety signal in terms of an increased proportional reporting ratio (PRR). Conclusions: The safety profile described in the Summary of Product Characteristics, in general, is confirmed by data from spontaneous reporting. No safety concerns were identified.

scholarly journals P647 Post-marketing evaluation of reported adverse events of a multi-strain probiotic product confirms that change in manufacturing site had no impact on safety profile

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S534-S535
Author(s):  
V Panetta ◽  
I Simonelli ◽  
A Bacchieri ◽  
S Papetti ◽  
E De Stefani ◽  
...  
Keyword(s):  
Adverse Events ◽  
Safety Profile ◽  
System Organ Class ◽  
Safety Report ◽  
Post Marketing Surveillance ◽  
The Us ◽  
The Usa ◽  
Post Marketing ◽  
Probiotic Product ◽  
System Organ

Abstract Background In 2016, the manufacturing site of the multi-strain probiotic product VSL#3 changed. The present work is aimed at verifying if this change had an impact on the safety profile of the product. Methods The safety reports from post-marketing surveillance in the USA received by Alfasigma in the years 2014–2015 were compared with those received in the years 2017–2018. 2016 was not considered, because the product on the market during this year could likely come from both manufacturing sites. VSL#3 is sold in the US market as a medical food. Most of the reports were from consumers and were not medically confirmed. However, this happened in both periods, so no bias is introduced in the comparison. Each single safety report contained one or more adverse events (AEs), coded with MedDRA. The comparison between the two periods concerned primarily the number of safety reports in relation to the number of units sold. Given the similarity of trends between the total number of safety reports and sales in the two periods, the frequencies of the AEs and serious AEs were also compared at the System Organ Class (SOC) and Preferred Term (PT) level. Results More than 70% of subjects reporting an AE were women in both periods under comparison; mean age was 58; phone was the most frequent means (overall 76%). Table 1 summarises the main results. Sales and number of safety reports were higher in the second than in the first period. However, the ratio between number of reports and sales was higher in the 2014–2015 period compared with the 2017–2018 period: 3.5 vs. 2.9 reports per 10,000 units sold, respectively. Similar results were obtained when stratifying the described ratios by formulation. The percentages of reports with at least one serious AE were respectively 3.2% in the first period and 2.5% in the second. The two periods appeared to be similar even with respect to the percentages of AEs and serious AEs by SOC and PT, being the AEs under the Gastrointestinal SOC the most frequently reported, as expected. Conclusion The analyzed data show that the manufacturing site change had no impact on the safety profile of VSL#3.

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