scholarly journals The Role of Checkpoint Inhibitors in Adults with Classical Hodgkin Lymphoma; A Systematic Review and Meta-Analysis of Phase II and III Clinical Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Yazan Samhouri ◽  
Muhammad Yasir Anwar ◽  
Ali Younas Khan ◽  
Urwat Til Vusqa ◽  
Iqraa Ansar ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Classical Hodgkin Lymphoma ◽  
Programmed Death ◽  
Phase Ii And Iii

Introduction The ability of the neoplastic cells to escape from immune surveillance has been considered as a hallmark of cancer. The upregulation of programmed death-1 (PD-1) and programmed death ligand-1/2 (PDL-1) axis is a major immune escape pathway in multiple malignancies including classical hodgkin lymphoma (cHL). Disruption of PD1-PDL1/2 pathway using checkpoint inhibitors (CPIs) leads to reactivation of immune cells to attack malignant cells. CPIs have been studied in cHL in different settings. Here in, we did a systematic review and meta-analysis of phase II and III clinical trials that looked at the efficacy of CPIs in cHL Methods We did a comprehensive literature search, using 4 major databases (pubmed, embase, chocrane, and clinialtrials.gov). We used MeSH terms and related keywords that included all CPIs in generic and trade names, and cHL. We included phase II and III prospective clinical trials in patients > 18 year-old. We excluded case reports, case series, review articles, retrospective and observational studies, and phase I clinical trials. Initial search resulted in 1647 articles. After applying the inclusion and exclusion criteria, we had 13 articles that we explored in details. We stratified the articles according to CPIs and did a pooled-analysis of the complete response (CR) rate. Medcalc was used to do the statistical analysis. Results Of those 13 clinical trials, we had 12 phase II trials and 1 phase III trial. Nivolumab was studied in 7 trials (n=568), pembrolizumab in 5 trials (n=427), and camrelizumab in 1 trial (n=86). Table 1 shows the characteristics of these trials. (table 1) Four studies evaluated the efficacy of nivolumab in the relapsed/refractory (RR) setting. Armand et al (2018) evaluated the efficacy of nivolumab after autologous hematopoietic stem cell transplantation (auto-HSCT), the cohort in this study was divided into 3 groups: patients who received brentuximab vedotin (BV) after auto-HSCT, patients who are BV naïve, and patients who received BV before and/or after auto-HSCT. Overall response rate (ORR) and CR were 68% and 13%, 65% and 29%, 73% and 12%, respectively. Maruyama et al (2017) reported ORR and CR of 81.3% and 25%, in 16 Japanese patients received nivolumab in combination with BV. The ORR and CR in the remaining 2 trials were: 82% and 59%, and 85% and 67%. In the frontline setting, nivolumab showed ORR and CR of 84% and 67% (Ramchandren et al, 2019), 96%-100% and 53-85% (Brockelmann et al, 2019 in 2 different dosing regimens), and 100% and 72% (Yasenchack et al, 2019). Pooled analysis of all nivolumab trials showed CR rate of 47.4 % (95% CI 29.0-66.1) (figure 1) Pembrolizumab was evaluated in 4 clinical trials in the RR setting. Armand et el (2019) reported CR rate of 83% in 25 patients. Chen et al (2019) reported ORR and CR of 76.8 % and 26.1% in patients who relapsed after auto-HSCT and BV, 66.7% and 25.9% in patients ineligible for HSCT, and 73.3% and 31.7% in patients who relapsed after auto-HSCT with no prior exposure to BV. In combination with gemcitabine, vinorelbone , and doxorubicin, pembrolizumab showed ORR and CR of 100% and 93%, respectively. The only phase III clinical trial compared pembrolizumab vs BV in the RR setting showed ORR of 65.6% vs 54% and CR of 24.5% vs 24%, respectively. Only one study evaluated pembrolizumab in the frontline setting, ORR and CR of 100% in 30 patients received 3 cycles of pembolizumab followed by 4-6 cycles of doxorubicin, vinblastine, and dacarbazine. Pooled analysis of all pembrolizumab trials showed CR rate of 54.4% (95% CI 32.6-77.2) (figure 2) Only one trial evaluated the role of camrelizumab as monotherapy or in combination with decitabine. The combination regimen showed ORR and CR of 95% and 71% in CPIs naïve patients, and 52% and 28% in patients previously received CPIs. Camrelizumab monotherapy showed ORR and CR of 90% and 32% in CPIs naïve patients. Conclusion CPIs in cHL have showed high rates of response in the frontline and RR settings, with fairly acceptable toxicity profile. Their efficacy was studied post HSCT and BV, in BV naïve patients, and in HSCT-ineligible patients. Pembrolizumab and nivolumab were the 2 most studied CPIs. Future direction should focus on more studies in the frontline setting, the role of combined CPIs with other CPIs or with novel agents, to spare this relatively young population the long term toxicity of chemotherapy. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.Fazal:Jansen:Speakers Bureau;Jazz Pharma:Consultancy, Speakers Bureau;Stemline:Consultancy, Speakers Bureau;Glaxosmith Kline:Consultancy, Speakers Bureau;Gilead/Kite:Consultancy, Speakers Bureau;Amgen:Consultancy, Speakers Bureau;Novartis:Consultancy, Speakers Bureau;Agios:Consultancy, Speakers Bureau;BMS:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene:Speakers Bureau;Karyopham:Speakers Bureau;Incyte Corporation:Consultancy, Honoraria, Speakers Bureau;Takeda:Consultancy, Speakers Bureau.

PrabotulinumtoxinA-xvfs for the Treatment of Moderate-to-Severe Glabellar Lines

2020 ◽  
pp. 106002802094352
Author(s):  
Mary B. Gadarowski ◽  
Rima I. Ghamrawi ◽  
Sarah L. Taylor ◽  
Steven R. Feldman
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Data Extraction ◽  
Botulinum Toxin Type A ◽  
Botulinum Toxin Type ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Study Selection ◽  
Pubmed Database ◽  
Phase Ii And Iii

Objective: PrabotulinumtoxinA-xvfs (Jeuveau), a botulinum toxin type A, was approved by the Food and Drug Administration for the temporary improvement in the appearance of moderate-to-severe glabellar lines in February 2019. This article will review phase II and III clinical trials to assess the efficacy, safety, and clinical application of this novel, aesthetic-only drug. Data sources: A systematic literature review was performed using the terms “glabellar lines AND prabotulinumtoxinA” in the PubMed database. ClinicalTrials.gov was searched to identify nonpublished studies. Study Selection and Data Extraction: Articles written in English between November 2019 and June 2020 discussing phase II and phase III clinical trials were evaluated. Data Synthesis: By the primary efficacy end point on day 30, more patients achieved a greater than 2-point improvement on the Glabellar Line Scale (GLS) at maximum frown compared with baseline on day 0. The proportions of participants who responded to treatment with prabotulinumtoxinA were 67.5% and 70.4% versus 1.2% and 1.3% in placebo groups across 2 identical clinical trials ( P < 0.001). Patients receiving prabotulinumtoxinA experienced greater improvement in GLS at maximum frown on day 30 (87.2%) compared with onabotulinumtoxinA (82.8%) and placebo (4.2%; P < 0.001). PrabotulinumtoxinA was well tolerated across all studies. Relevance to Patient Care and Clinical Practice: This review provides a detailed analysis of the safety and efficacy of prabotulinumtoxinA-xvfs and includes special considerations to help guide patients and clinicians. Conclusion: PrabotulinumtoxinA is a safe and effective new addition to the repository of available treatments for the appearance of glabellar lines.

Treating Psoriasis With Halobetasol Propionate and Tazarotene Combination: A Review of Phase II and III Clinical Trials

2020 ◽  
Vol 54 (9) ◽  
pp. 872-878
Author(s):  
Vignesh Ramachandran ◽  
Brooke Bertus ◽  
Arjun M. Bashyam ◽  
Steven R. Feldman
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Plaque Psoriasis ◽  
Patient Adherence ◽  
Treatment Success ◽  
Phase Iii ◽  
Global Assessment Scale ◽  
Once Daily ◽  
Psoriasis Treatment ◽  
Phase Ii And Iii

Objective: To review phase II and III clinical trial data to evaluate the efficacy and safety of the halobetasol propionate/tazarotene (HP/TAZ) combination lotion (Duobrii), a medication approved by the Food and Drug Administration in April 2019 for adults with plaque psoriasis. Data Sources: A systematic search (January 2005 to July 2019) of MEDLINE (PubMed) and EMBASE databases was performed using the terms halobetasol, tazarotene, halobetasol/tazarotene, Duobrii, and IDP-118. Study Selection and Data Extraction: Relevant English-language articles reporting on phase II and phase III clinical trials were included. Data from the individual trials were extracted independently and then cross-checked to ensure accuracy. Data Synthesis: HP/TAZ was safe and efficacious compared with HP alone, TAZ alone, or vehicle. More patients achieved treatment success, described as a ≥2-grade improvement on Investigator Global Assessment Scale, over 8 weeks of treatment and at the 4-week follow-up after treatment cessation. The most common adverse events were dermatitis, pain, and pruritus, which occurred more often in the TAZ groups compared with the HP/TAZ cohorts. Relevance to Patient Care and Clinical Practice: The once-daily HP/TAZ combination lotion simplifies psoriasis treatment and may facilitate adherence, which may improve psoriasis outcomes. Conclusions: HP/TAZ combination lotion is efficacious and safe for plaque psoriasis treatment, with more patients achieving end points and fewer side effects than in HP, TAZ, or vehicle-treated controls. Drug synergy may play a role. Importantly, patient adherence to a once-daily combinational therapy is likely to contribute to efficacy.

Evolution of statistical methodology and design of phase II/III clinical trials in non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7108-7108 ◽  
Author(s):  
R. K. Bagai ◽  
A. Dowlati
Keyword(s):  
Clinical Trials ◽  
Survival Time ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Iii ◽  
Type I ◽  
Phase Ii Trials ◽  
Improvement In Survival ◽  
Phase Ii And Iii ◽  
Phase Iii Studies

7108 Background: A significant heterogeneity exists in the design and reporting of phase II and III therapeutic clinical trials in NSCLC. This has led to difficulty in interpretation of these trials leading to over- or underestimation of therapeutic efficacy. We set out to investigate the statistical methodology and design reporting of chemotherapeutic trials in NSCLC published in the Journal of Clinical Oncology (JCO) over 20 years. Methods: We identified all phase II and III NSCLC chemotherapy trials published in the JCO from January 1983 to August 2005. All manuscripts were reviewed to evaluate components of statistical design that were reported, including: sample size calculation, power, type I error, single or multiple drug trials, relative response sought in phase II trials and improvement in survival time or response rate sought in phase III trials. Results: One hundred forty eight trials were identified. 52% of studies were phase III and 48% were phase II. The majority (78%) were conducted in advanced stage NSCLC. Sample size calculations were reported for only 58% of phase III studies and 31% of phase II studies. Power was reported in 66% of phase III studies and 13% of phase II trials. Type I error was reported in 47% of phase III studies and 17% in phase II studies. 60% of phase III trials defined endpoints (percentage improvement in survival time, improvement in survival time in months or increase in response rate). 41% of phase II trails defined the target response rate, ranging from response rates of 15% to 70%. The frequency of adequate reporting of statistical design was shown to increase from 31% in 1990–1995 to 64% in 2000–2005 ( table ). Conclusions: Significant heterogeneity exists in trial design and reporting of phase II and III trials in NSCLC. This impacts the ability to adequately interpret these studies. More widespread application of statistical methods in planning and reporting of lung cancer clinical trials are necessary to increase reliability of data. [Table: see text] No significant financial relationships to disclose.

Risk of fall and clinical fracture associated with androgen receptor inhibitors: A systematic review and meta-analysis.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 71-71
Author(s):  
Zin Myint ◽  
Harry D. Momo ◽  
Danielle E. Otto ◽  
Donglin Yan ◽  
Robert S. DiPaola ◽  
...  
Keyword(s):  
Systematic Review ◽  
Androgen Receptor ◽  
Phase Ii ◽  
Fixed Effects ◽  
Mixed Model ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Phase Iii ◽  
High Grade ◽  
Increased Risk

71 Background: Patients treated with androgen receptor inhibitors (ARIs) report a higher incidence of falls; although a potential mechanism of action is unknown. This systematic review evaluates the relative risk (RR) of fall and fracture in prostate cancer (PCa) patients that receive ARIs. Methods: We conducted a comprehensive literature search using Cochrane, Scopus and MedlinePlus databases from inception through August 2019, and evaluated all published prospective phase II, III and IV randomized controlled trials that treated PCa patients with ARIs. Reported fall and fractures as adverse events (AEs) were extracted for analysis. Retrospective, phase I, non-randomized phase II, and studies with control arms that used one of the ARIs were excluded. A mixed effects model was used to estimate effects of ARI on the RR, with the included studies treated as random effects and study arms treated as fixed effects in the pooled analysis. Sample size for each study was used to weight the mixed model. Results: Eleven studies met our inclusion criteria. The total population was 11,382; 6536 were in the ARI arm and 4846 in the control (CTL) arm. Study types were: 8 phase III; 2 phase II; 1 phase IV. Subjects in the ARI arm received enzalutamide, apalutamide or darolutamide in combination with androgen deprivation therapy or other enzalutamide combinations while in the CTL arm received placebo, bicalutamide or abiraterone. Treatment duration ranged from 5.4 to 20.5 mo for ARI vs. 5.4 to 18.3 mo for CTL. The reported incidence of fall was 481 (7.4%) in ARI and 201 (4.1%) for CTL. The incidence of fracture was 204 (3.1%) in ARI and 93 (1.9%) in control. The use of ARI was associated with an increased risk: all fall grades (RR 1.83; 95% CI 1.56-2.15; p <0.01); high grade fall (RR 1.69; 95% CI 1.09 – 2.62; p=0.019); all grade fracture (RR 1.56; 95% CI 1.23-1.97; p <0.01) and likely high grade fracture (RR 1.62; 95% CI 0.97 – 2.69; p=0.063). Conclusions: The use of ARI significantly increases falls and fractures in PCa patients as assessed by this meta-analysis study. Further studies would be warranted to identify and understand potential mechanisms and develop strategies to decrease falls and fractures associated with ARI use.

Magnitude of benefit of the addition of bevacizumab (BEVA) to first-line chemotherapy (CT) for advanced/metastatic colorectal cancer (MCRC): Meta-analysis of randomized clinical trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15021-e15021
Author(s):  
V. Vaccaro ◽  
F. Cuppone ◽  
F. Loupakis ◽  
M. Milella ◽  
P. Carlini ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Clinical Trials ◽  
Regression Analysis ◽  
Phase Ii ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Meta Regression ◽  
Meta Regression Analysis

e15021 Background: The monoclonal antibody against vascular endothelial growth factor BEVA has recently demonstrated to improve survival for MRC patients (pts). Nevertheless, the magnitude of the provided benefit in the daily practice is still controversial. In order to quantify the benefit of adding BEVA to CT for MCRC, a literature-based meta-analysis was conducted. Methods: Survival Hazard Ratios (HR) were extracted from prospective, randomized clinical trials (RCTs, either phase II/III) reports. HR and event-based relative risks (RR) with 95% confidence intervals (CI) were derived through a random-effect model. Differences in primary (progression-free- and overall-survival, PFS/OS) and secondary outcomes (overall, partial and complete response rates, ORR/PR/CR) were explored. Absolute differences (AD) and the number of patients needed to treat (NNT) were calculated. Heterogeneity test and a meta-regression analysis with clinical predictors for outcomes were conducted as well. A sensitivity analysis according to the trial phase-design was accomplished. Results: Five trials (2,728 pts), 2 phase II (313 pts) and 3 phase III (2,415 pts), were gathered. No significant interaction was found in the sensitivity analysis between phase II and III, although a trend showed a better PFS results for BEVA in phase II trials (p=0.057). At the meta-regression analysis female gender and rectal primary site were significant predictors for PFS (p=0.003, p=0.005). Toxicity analysis is ongoing. Conclusions: Although concerns regarding costs and toxicities still exist, BEVA significantly improves the outcome of untreated MCRC pts. The absolute benefit provided into an unselected population for molecular features should be considered of paramount importance for advanced disease. [Table: see text] No significant financial relationships to disclose.

Efficacy of Oxaliplatin Plus Capecitabine or Infusional Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer: A Pooled Analysis of Randomized Trials

2008 ◽  
Vol 26 (36) ◽  
pp. 5910-5917 ◽  
Author(s):  
Hendrik-Tobias Arkenau ◽  
Dirk Arnold ◽  
Jim Cassidy ◽  
Eduardo Diaz-Rubio ◽  
Jean-Yves Douillard ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Randomized Phase Ii ◽  
Hand Foot Syndrome ◽  
Toxicity Analysis ◽  
Grade 3 ◽  
Phase Ii And Iii

PurposeSix randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX.Patients and MethodsThis analysis compared all published CAP/OX versus infusional FU/OX regimens. A total of 3,494 patients (FU, n = 1,737; CAP, n = 1,757) were analyzed for response rate (RR), progression-free (PFS), overall survival (OS), and toxicity.ResultsThe fixed-effect pooled estimate for RR showed higher RR for FU-based regimens (Odds ratio [OR] = 0.85; 95% CI, 0.74 to 0.97; P = .02) whereas the analysis of chemotherapy-only trials, excluding the bevacizumab containing NO16966 and TREE 2 trials, led to an OR of 0.74 (95% CI, 0.60 to 0.92; P = .007). However, for PFS (hazard ratio [HR] = 1.04; 95% CI, 0.96 to 1.12; P = .17) and OS (HR = 1.04; 95% CI, 0.95 to 1.12; P = .41) all models suggested similar outcome within the range of noninferiority. Grade 3/4 toxicities (thrombocytopenia—HR = 2.07, 95% CI, 1.42 to 3.03; P < .0002; diarrhea—HR = 1.34; 95% CI, 1.08 to 1.66; P < .0009; and grade 2/3 hand-foot-syndrome [HFS]—HR = 3.54; 95% CI, 2.07 to 6.05; P < .00001) were less prominent with FU-based regimens whereas neutropenia (HR = 0.15; 95% CI, 0.11 to 0.19; P < .00001) was lower in the CAP regimens.ConclusionThe combination of CAP and OX resulted in lower RR, but this did not affect PFS and OS, which were similar in both treatment arms. The toxicity analysis showed the characteristic toxicity of each of the different FU schedules, with thrombocytopenia and HFS consistently more prominent in the CAP regimens.

scholarly journals Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials

2018 ◽  
Author(s):  
Antonino Grassadonia ◽  
Isabella Sperduti ◽  
Patrizia Vici ◽  
Laura Iezzi ◽  
Davide Brocco ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Phase Iii ◽  
Cochrane Central Register

Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p&lt;0.001 and HR 0.77, p&lt;0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p&lt;0.012), with the exception of melanoma (in women, HR 0.80, p=0.006). PFS was longer in men than in women (HR 0.67, p&lt;0.001 and HR 0.77, p=0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs.

scholarly journals Efficacy and Safety Profile of Ixazomib Based Regimens in Relapsed/Refractory Multiple Myeloma: A Meta-Analysis of Clinical Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-21
Author(s):  
Ahmad Iftikhar ◽  
Muhammad Ashar Ali ◽  
Anum Javaid ◽  
Muhammad Abu Zar ◽  
Atif Sohail ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Safety Profile ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Case Series ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Grade 3

Background: Multiple myeloma (MM) is an incurable disease, and clinical trials with newer agents have shown improved patient outcomes. There is a need for effective and tolerable treatment for patients with relapsed/refractory MM (RRMM). Proteasome inhibitors (bortezomib, carfilzomib, ixazomib) remain an integral part of regimens used in RRMM or newly diagnosed (ND) MM. This meta-analysis aims to assess the efficacy and safety of ixazomib (Ixa) based regimens in RRMM. Methods: A comprehensive literature search was performed on PubMed, Cochrane, Embase, Web of Science, and clinicaltrials.gov. We used MeSH and Emtree terms, "ixazomib" AND "multiple myeloma" from the inception of literature till 06/01/2020. We screened 1529 articles and included 3 randomized clinical trials (RCT, N=907) and 8 non-randomized clinical trials (NRCT, N=321). We excluded case reports, case series, review articles, meta-analysis, observational studies, and clinical trials that didn't provide data about the efficacy and safety of Ixa in RRMM. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: In 11 clinical trials (N=1228), the age range of patients was 30-91 years. In Phase III RCTs (N=837) comparing Ixa + Lenalidomide (Len) + dexamethasone (Dex) vs. placebo + Len + Dex, risk ratio of overall response rate (ORR), complete response (CR), and very good partial response (VGPR) were 1.14 (95% CI=1.05-1.24, I2=80%), 1.87 (95% CI=1.17-2.99, I2=0), and 1.15 (95% CI=0.95-1.40, I2=0), respectively in favor of Ixa + Len + Dex. (Fig 1-3) Grade 3 or higher treatment-related adverse events (TRAEs) thrombocytopenia, diarrhea, and rash were reported in 20%, 5.7% and 6.4% of the patients in the Ixa group vs. 10%, 2.1%, and 2.8% in the placebo group, respectively. In a Phase II RCT by Kumar et al (N=70) comparing the Ixa dosage, 4 mg Ixa + Dex yielded an ORR of 31%, CR 2.8%, and VGPR 17.1%, while 5.5 mg Ixa yielded improved ORR of 54%, CR 2.8%, and VGPR 25.7%. In a NRCT by Costello et al. (N=6), Ixa + daratumumab (Dara) + Pom + Dex yielded 100% ORR, CR 5% (95% CI=0.17-0.83), and VGPR 50% (95% CI=0.17-0.83). ≥Grade 3 TRAEs were hypertension (16%), and hematological (33%). Among 417 patients from two RCT in single arm who received Ixa + Len + Dex, pooled ORR was 70% (95% CI=0.53-0.82, I2=84%), pooled CR 11% (95% CI=0.8-0.14, I2=0), and pooled VGPR was 29% (95% CI=0.18-0.43, I2=66%). In a NRCT by Dhakal et al. (N=19), Ixa + bendamustine + Dex yielded an ORR 58% (95% CI=0.36-0.77), CR 0, and VGPR 11% (95% CI =0.03-0.34). ≥Grade 3 TRAEs were neutropenia 31%, thrombocytopenia 52%, and diarrhea 10%. In 2 NRCT (N=106), Ixa + cyclophosphamide (Cyc) + Dex yielded a pooled ORR 52% (95% CI=0.42-0.61, I2=0), CR 4% (95% CI=0.01-0.10, I2=0), and VGPR 17% (95% CI=0.11-0.25, I2=0). ≥Grade 3 TRAEs were thrombocytopenia (15%), and upper abdominal pain (4%). In a NRCT by Ludwig et al. (N=90), Ixa + thalidomide (Thal) + Dex yielded an ORR 51% (95% CI=0.41-0.61), CR 9% (95% CI=0.5-0.17), and VGPR 14% (95% CI=0.09-0.23). ≥Grade 3 TRAEs were anemia (17.8%), and infections (16.1%). In a NRCT by Krishnan et al. (N=31), Ixa + Pomalidomide (Pom) + Dex yielded an ORR 48% (95% CI=0.32-0.65) and VGPR 16% (95% CI=0.07-0.33). (Fig 4-6) ≥Grade 3 TRAEs were neutropenia (10%), and lymphopenia (35%). In 2 NRCT by Kumar et al. (N=70) of two drugs combination, Ixa + Dex yielded a pooled ORR 43% (95% CI=0.28-0.59, I2=47%), pooled CR 1% (95% CI=0-0.09, I2=0), and pooled VGPR 24% (95% CI=0.16-0.36, I2=0). ≥Grade 3 TRAEs were hematological (28%), and non-hematological (22.8%). In 2 NRCT of Ixa monotherapy (N=69), pooled ORR was 17% (95% CI=0.10-0.28, I2=0), and pooled CR 6% (95% CI=0.2-0.22, I2=0). (Fig 4-6) ≥Grade 3 TRAEs were anemia (11%), thrombocytopenia (5.4%), and neutropenia (2.7%). Conclusion: Our study provides useful insight into relative efficacy of various Ixa regimens for the treatment of RRMM. The pooled analysis of RCT showed that the combination of Ixa + Len + Dex yielded better response as compared to placebo. In the pooled analysis of outcomes in single arm NRCT, Ixa + Dara + Pom + Dex and Ixa + Len + Dex showed better efficacy outcomes as compared to Ixa + Dex in combination with Thal, Cyc, or Bendamustin. Three drugs Ixa combination regimens had better efficacy as compared to two drugs combination of Ixa + Dex and Ixa monotherapy. Ixa was well tolerated with acceptable safety profile. Additional multicenter, double-blind clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

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