scholarly journals Three years efficacy and safety of Takeda’s dengue vaccine candidate (TAK-003)

2021 ◽  
Author(s):  
Luis Rivera ◽  
Shibadas Biswal ◽  
Xavier Sáez-Llorens ◽  
Humberto Reynales ◽  
Eduardo López-Medina ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Efficacy And Safety ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Post Vaccination ◽  
Safety Risks ◽  
Long Term Follow Up ◽  
To Receive

Abstract Background Takeda’s live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across eight dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year post-vaccination. This exploratory analysis provides an update with cumulative and third year data. Methods Healthy 4–16 year-olds (n=20,099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific RT-PCR. Results Cumulative efficacy after three years was 62.0% (95% confidence interval: 56.6%, 66.7%) against virologically-confirmed dengue (VCD) and 83.6% (76.8%, 88.4%) against hospitalized VCD. Efficacy was 54.3% (41.9%, 64.1%) against VCD and 77.1% (58.6%, 87.3%) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9%, 70.1%) against VCD and 86.0% (78.4%, 91.0%) against hospitalized VCD in seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5%, 54.7%), while efficacy against hospitalized VCD was sustained at 70.8% (49.6%, 83.0%). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (i.e. second half of the three years following vaccination), but none were related. No important safety risks were identified. Conclusions TAK-003 was efficacious against symptomatic dengue over three years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.

Nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (NSCLC): 4-year update from CheckMate 227.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9016-9016
Author(s):  
Luis G. Paz-Ares ◽  
Tudor-Eliade Ciuleanu ◽  
Jong-Seok Lee ◽  
Laszlo Urban ◽  
Reyes Bernabe Caro ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Programmed Death ◽  
Long Term Follow Up ◽  
To Receive ◽  
Clinical Trial Information

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 < 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 < 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 < 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]

scholarly journals Efficacy and safety of trabeculectomy with mitomycin C for childhood glaucoma: a study of results with long-term follow-up

Clinics ◽  
2008 ◽  
Vol 63 (4) ◽  
pp. 421-426 ◽  
Author(s):  
Jair Giampani Junior ◽  
Adriana Silva Borges-Giampani ◽  
José Carlos Eudes Carani ◽  
Ernst Werner Oltrogge ◽  
Remo Susanna Junior
Keyword(s):  
Mitomycin C ◽  
Efficacy And Safety ◽  
Long Term Follow Up

scholarly journals Side Effects Following Administration of the First Dose of Oxford-AstraZeneca’s Covishield Vaccine in Bangladesh: A Cross-Sectional Study

2021 ◽  
Vol 13 (4) ◽  
pp. 888-901
Author(s):  
Nishat Jahan ◽  
Fahad Imtiaz Rahman ◽  
Poushali Saha ◽  
Sadia Afruz Ether ◽  
ASM Roknuzzaman ◽  
...  
Keyword(s):  
Side Effects ◽  
Rapid Development ◽  
Age Groups ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Post Vaccination ◽  
Long Term Follow Up ◽  
Larger Sample

In response to the raging COVID-19 pandemic, Bangladesh started its vaccine administration in early 2021; however, due to the rapid development and launch of the vaccines in the market, many people had concerns regarding the safety of these vaccines. The purpose of this study was to evaluate the side effects that were experienced by the Bangladeshi residents after receiving the first dose of the Oxford-AstraZeneca’s Covishield vaccine (ChAdOx1nCoV-19). The study was conducted using both online and printed questionnaires and the data were analysed using SPSS. The results included the responses of 474 vaccine recipients from March–April 2021. Pain at the site of injection, fever, myalgia, fatigue and headache were the most commonly reported symptoms, and the overall side effects were found to be significantly more prevalent in the younger population (p ≤ 0.05). These findings were consistent with the results indicated by the clinical trial of ChAdOx1nCoV-19. Logistic regression analysis further revealed that compared to people aged 70 years or above, the incidence of reported side effects was significantly higher in people aged 18–30 years (odds ratio (OR) = 8.56), 31–40 years, (OR = 5.05), 41–50 years (OR = 4.08), 51–60 years (OR = 3.77) and 61–70 years (OR = 3.67). In addition, a significantly higher percentage of female participants suffered from post-vaccination side effects compared to males (OR = 1.51). It was concluded that the Covishield vaccine was well-tolerated among people of different age groups. Nevertheless, further long-term follow-up study with a larger sample size is warranted to establish the long-term safety of the COVID-19 vaccine.

scholarly journals THALIDOMIDE FOR PATIENTS WITH THALASSEMIA INTERMEDIA: A RETROSPECTIVE MULTICENTER CLINICAL STUDY

2020 ◽  
Vol 12 (1) ◽  
pp. e2020021
Author(s):  
Kun Yang ◽  
Yi Wu ◽  
Yali Zhou ◽  
Tianhong Zhou ◽  
Li Wang ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Laboratory Data ◽  
Drug Discontinuation ◽  
Therapeutic Effects ◽  
Efficacy And Safety ◽  
Thalassemia Intermedia ◽  
Short Term ◽  
Long Term Follow Up

Objective: This study focused on the efficacy and safety of thalidomide for patients with thalassemia intermedia (TI) in a multicenter trial. Methods：Clinical and laboratory data of 62 patients subjected to thalidomide therapy in four centers were retrospectively analyzed. We evaluated the efficacy and safety of thalidomide in the short-term (three months) and long-term follow-up (12 and 24 months). Response to thalidomide was defined as follows: Main Responder (MaR) showing an increase in Hb level of >2.0 g/dl or removal from blood transfusion and Minor Responder (MiR) achieving elevated hemoglobin (Hb) level of 1.0-2.0 g/dl or ≥50% reduction in blood transfusion frequency. Results：The overall response rate (ORR) of 62 patients with TI was 93.5% (58/62), with MaR and MiR rates accounting for 62.9% (39/62) and 30.6% (19/62) in short-term follow-up and 66.1% (41/62) and 27.4% (17/62) in long-term follow-up, respectively. The clinical response during long-term follow-up was maintained and the Hb level remained stable during the observation period. The response was still observed in patients with dose reduction despite a slight decrease in Hb level. However, Hb decreased rapidly to the baseline level after drug discontinuation. No effect of thalidomide on spleen size in nonsplenectomized patients was evident. Minimal side-effects were documented throughout, except peripheral neurotoxicity in one patient. Nevertheless, the mean serum ferritin (SF) level was significantly increased after treatment. Conclusion: Thalidomide had significant therapeutic effects on patients with TI, and the response was sustained with acceptable short-term and long-term adverse reactions. While these preliminary results support the potential long-term efficacy and safety of thalidomide as a therapeutic agent for TI, several issues need to be addressed before its application in the clinic.

scholarly journals Efficacy and safety of high-dose chemotherapy with in vivo purged auto-SCT in relapsed follicular lymphoma: long-term follow-up

2009 ◽  
Vol 45 (6) ◽  
pp. 1119-1120 ◽  
Author(s):  
M Magni ◽  
M Di Nicola ◽  
C Carlo-Stella ◽  
L Devizzi ◽  
A Guidetti ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Efficacy And Safety ◽  
Long Term Follow Up

Long-term follow-up for efficacy and safety of treatment of retinitis pigmentosa with valproic acid

2013 ◽  
Vol 97 (7) ◽  
pp. 895-899 ◽  
Author(s):  
Sheena Bhalla ◽  
Deval Joshi ◽  
Shaminder Bhullar ◽  
Daniel Kasuga ◽  
Yeonhee Park ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Retinitis Pigmentosa ◽  
Efficacy And Safety ◽  
Long Term Follow Up

Follow-up Analysis of a Randomized Comparison of Prolonged Myelosuppressive Maintenance Therapy Versus Intensive Consolidation Therapy as Postremission Therapy in AML.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1056-1056
Author(s):  
Utz O. Krug ◽  
Maria Cristina Sauerland ◽  
Bernhard J Woermann ◽  
Wolfgang Berdel ◽  
Wolfgang Hiddemann ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Maintenance Therapy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Postremission Therapy ◽  
To Receive

Abstract Abstract 1056 Poster Board I-78 Introduction: We previously showed that a prolonged myelosuppressive maintenance chemotherapy was superior to S-HAM as a postremission therapy in patients > 16 years of age with AML after a TAD-HAM double induction therapy and TAD consolidation chemotherapy with regard to relapse-free survival (RFS) and borderline significance of the overall survival (OS) in responding patients (Buchner et al., JCO 2003, 21:4496-4504). Here we present long-term follow-up data with a median follow-up of 7.9 years from diagnosis and 7.1 years from the date of complete remission. Patients and Methods: Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were upfront randomized in the AMLCG1992 study of the German AML Co-operative Group to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age ≥ 60 years] x 6 (HAM in patients ≥ 60 years only in case of blast persistence on day 16 of therapy) induction, TAD consolidation, and monthly maintenance with cycles of cytarabine combined with either daunorubicin (course 1), 6-thioguanine (course 2), cyclophosphamide (course 3), and again 6-thioguanine (course 4), and restarting with course 1 for 3 years, or to receive TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age ≥ 60 years) x 8 instead of maintenance. Results: A total of 576 patients (69.2%) achieved a complete remission (CR) those were 294 of 429 (68.5%) patients randomized to receive maintenance and 282 of 403 (70.0%) patients randomized to receive intensive consolidation S-HAM (p=n.s.). 190 patients received maintenance therapy as intended and 135 patients received an intensive consolidation therapy as intended. This prolonged follow-up analysis verified the superior relapse-free survival in all patients in the maintenance arm (10-year RFS 30.0 ± 5.6 versus 19.9 ± 6.1 %, p = 0.015). Stratified by age, the 10-year RFS was superior in younger patients < 60 years (36.9 ± 7.1 versus 25.2 ± 8.0 %, p = 0.038) and borderline significant in elderly patients (17.2 ± 4.5 versus 6.8 ± 6.2 %, p = 0.075). A subgroup analysis of known risk groups (lactate dehydrogenase (LDH) level < 700U/l versus ≥ 700U/l at diagnosis, cytogenetic risk profile, bone marrow blasts on day 16 after the start of the induction therapy) revealed a superior RFS in the subgroup of patients with LDH level > 700 U/l at diagnosis (33.5 ± 12.3 versus 18.2 ± 9.5 %, p = 0.043). This superior RFS also translated into a superior 10-year relapse-free interval (RFI) of all responding patients in the maintenance arm (35.7 ± 6.3 versus 27.6 ± 5.9 %, p = 0.015) with borderline significance in younger patients (42.9 ± 7.4 versus 35.0 ± 7.4 %, p = 0.053) and a significant difference in elderly patients (20.6 ± 10.0 versus 8.4 ± 7.5 %, p = 0.043). In this updated analysis, there was a trend, but no significant difference in the OS (maintenance arm: 10-year OS 24.3 ± 4.8, intensive consolidation arm: 19.7 ± 4.7 %, p = 0.148), and we verified a trend for a better OS in responding patients for the maintenance arm (10-year OS in responding patients 33.6 ± 7.5 versus 28.5 ± 6.2 %, p = 0.093). The event-free survival (EFS) also showed a trend towards better EFS in the maintenance arm (10-year EFS 20.7 ± 4.2 versus 14.8 ± 4.1 %, p = 0.082) which was significant in elderly patients (10-year EFS 10.5 ± 5.5 versus 3.9 ± 3.7 %, p = 0.044). Discussion: This updated analysis with a long-term follow-up of median 7.9 years from diagnosis and 7.1 years from CR verified the superior RFS and the trend for enhanced OS in responding patients. These results suggest the superiority of a prolonged monthly myelosuppressive maintenance therapy as compared to intensive consolidation S-HAM after TAD-HAM induction and TAD consolidation. Disclosures: No relevant conflicts of interest to declare.

Radiation ±cisplatin for bulky stage IB cervical carcinoma; Long-term follow-up of a GOG trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5015-5015
Author(s):  
F. B. Stehman ◽  
S. Ali ◽  
D. G. Gallup ◽  
H. Key
Keyword(s):  
Cervical Carcinoma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stage Ib ◽  
Long Term Follow Up ◽  
Weekly Cycles ◽  
To Receive ◽  
Weekly Cisplatin

5015 Purpose: To confirm that concurrent cisplatin (CT) with radiation (RT) is associated with improved long-term progression-free survival (PFS), overall survival (OS), and decreased morbidity compared to RT stage IB bulky carcinoma of the cervix, when both groups’ therapy is followed by hysterectomy. Methods: Three hundred seventy-four patients entered this trial. There were 369 evaluable patients; 186 were randomly allocated to receive RT alone and 183 to receive CT+RT. Radiation dosage was 40 Gray (Gy) in 20 fractions followed by a single low dose-rate intracavitary application of 30 Gy to Point A. Chemotherapy consisted of cisplatin 40 mg/M2 every week for up to six weekly cycles. Total extrafascial hysterectomy followed the completion of RT by 3–6 weeks. Results: Preliminary results have been published, at which time there many censored observations and limited follow-up. Patient and tumor characteristics were well-balanced between the regimens. The median patient age was 41.5 years; 81% had squamous tumors; 59% were white. Median follow-up is 101 months. The relative risk for progression was 0.61 favoring CT+RT (95% confidence interval [CI]: 0.43–0.85, p < 0.004). At 72 months 71% of patients receiving CT+RT were predicted to be alive and disease-free when adjusting age and for tumor size compared to 60% of those receiving RT alone. The adjusted death hazard ratio was 0.63 (95% CI: 0.43–0.91, p < 0.015) favoring CT+RT. At 72 months, 78% of CT+RT patients were predicted to be alive compared to 64% of RT patients. An increased rate of early hematologic and gastrointestinal toxicity was seen with CT+RT. There was no detectable difference in the frequency of late adverse events. Conclusion: Concurrent weekly cisplatin with RT significantly improves long term PFS and OS when compared to RT alone. Serious late effects were not increased. The inclusion of hysterectomy has been discontinued on the basis of another trial. Pending further trials, weekly cisplatin with radiation is the standard against which other regimens must be compared. Key Words: Cervical carcinoma, chemoradiotherapy. No significant financial relationships to disclose.

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