scholarly journals Systematic Literature Review of the Clinical Efficacy, Safety, and Patient-Reported Outcomes of Treatments in Patients with Relapsed or Refractory Follicular Lymphoma after Two Prior Therapies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 40-40
Author(s):  
Qiufei Ma ◽  
Simarjeet Kaur ◽  
Angela Zhao ◽  
Jie Zhang ◽  
Roberto Javier Ramos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Literature Review ◽  
Patient Reported Outcomes ◽  
Pi3k Inhibitors ◽  
Emerging Compounds ◽  
Patient Reported ◽  
Car T ◽  
Duration Of Response ◽  
Anti Cd20

Introduction For patients (pts) with relapsed or refractory follicular lymphoma (r/r FL) beyond front-line therapy, there is no well-defined standard of care (SOC) treatment, especially in the third-line or later (3L+) setting. Treatment decisions for symptomatic patients depend on comorbidities, extent of disease, lines of prior therapy and duration of response to initial anti-CD20 containing treatment. Treatment options for 3L+ may include similar options to the ones in earlier lines, with a preference for non-cross-resistant schemes. Recently, a plethora of new compounds are being studied in clinical trials. A systematic literature review (SLR) was conducted to identify relevant evidence on clinical outcomes in pts with r/r FL, including conventional treatments and emerging compounds, within the 3L+ setting. Methods We performed a SLR on March 17, 2020. Clinical trials and observational studies were searched through Embase, PubMed, and Cochrane Central Register of Controlled Clinical Trials from 1998 to 2020, followed by relevant conference proceedings and regulatory documents. Evidence assessing any intervention as 3L+ FL and published in English language was included. If a study included broader indolent non-Hodgkin's lymphoma (iNHL) pts, only FL data was reported; if a study included pts with fewer than 3L+, 3L+ data was included, with mixed line results excluded. Conventional treatments, defined as approved or clinical guideline recommended treatments, included anti-CD20 monoclonal antibody (mAb)-containing regimen, mAb alone, chemotherapy alone, phosphatidylinositol 3-kinase (PI3K) inhibitors (idelalisib, copanlisib, duvelisib), lenalidomide + rituximab (R2), radio-immunotherapy (RIT) with yttrium-90 (90Y) ibritumomab tiuxetan, tazemetostat, autologous and allogeneic stem cell transplantation (auto- and allo-SCT). Emerging compounds included new treatments that are not approved but were tested in the context of clinical trials (bruton tyrosine kinase inhibitors, bortezomib, polatuzumab vedotin, daratumumab, inotuzumab, bi-specific T-cell engaging CD19 mAb, anti-CD19 chimeric antigen receptor T-cell [CAR-T] therapy). Results Of the 3747 publications identified, 74 studies assessing 26 treatment regimens, including conventional ones like rituximab (R)-containing immunochemotherapy to emerging compounds such as CAR-T therapies, were selected. Across the conventional regimens, 7 studies reported clinical trial data with relatively large 3L+ FL populations (Table 1). With R monotherapy, PI3K inhibitors and tazemetostat, the reported complete response (CR) rates and overall response rates (ORR) ranged from 1-20% and 34-77%, while median duration of response (mDOR) ranged between 7.9-16.3 months. Three clinical trials with PI3K inhibitors reported proportions of pts achieving a response of at least 6 months in duration ranging from 18-30%; median progression-free survival (mPFS) ranging from 8.3-11.2 months. For tazemetostat, mPFS was 11.0 months in EZH2 mutant vs 5.7 months in wild-type FL. With allo-SCT, 2-yr PFS rate was 88% and 57% for pts with CR and PR, respectively. Overall survival (OS) data varied: median overall survival (mOS) was 28-38 months for PI3K inhibitors while mOS was up to 85 months after allo-SCT, despite high non-relapse mortality (NRM) rates with most common causes of death being graft-versus-host disease (GvHD) and infections. Safety profiles were also different across treatments, with most common side effects being hepatotoxicity, diarrhea and infections (PI3K inhibitors) to GvHD (allo-SCT). Three trials presented patient-reported outcomes (PRO) data, all using the Functional Assessment of Cancer Therapy (FACT) questionnaire. Two studies with PI3K inhibitors demonstrated favorable or clinically significant improvement on pts quality of life (QoL), but 1 allo-SCT trial did not show a significant difference between baseline and 2 years post-transplant scores. Conclusion To our knowledge, this is the first SLR focusing on 3L+ treatments of FL. Heterogeneity in study design, patient population, safety profile and reported outcomes make it challenging to identify an optimal treatment regimen for FL in the 3L+ setting. More PRO data are needed considering the important role pt QoL plays in treatment selection. Disclosures Ma: Novartis:Current Employment.Kaur:Novartis:Current Employment.Zhao:Novartis:Current Employment.Zhang:Novartis:Current Employment.Ramos:Novartis:Current Employment.Kumar:Novartis:Current Employment.John:Novartis:Current Employment.Bubuteishvili Pacaud:Novartis:Current Employment.Forcina:Novartis:Current Employment.

Emerging trends and utilization of patient-reported outcomes (PROs) in clinical trials of chimeric antigen receptor (CAR) T-cell therapies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19142-e19142
Author(s):  
Anthony John Messina ◽  
Vasily Andrianov ◽  
Daniel Mazzolenis ◽  
Liat Vidal-Fisher
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Phase I ◽  
Patient Reported Outcomes ◽  
Utilization Rate ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Patient Reported ◽  
Car T ◽  
The Impact

e19142 Background: Patient-reported outcomes (PROs) are an important tool to assess the impact of new therapies on health-related quality of life (HRQoL). This study aimed to describe if and what PRO instruments are currently being utilized in CAR-T cell therapy studies in solid and hematological malignancies while assessing the patterns of inclusion and trends of HRQoL data reporting. Methods: We used Citeline to search for clinical trials between Jan 2008 - Jan 2020, excluding planned or terminated studies, non-oncology, non-treatment, and duplicates. Reviewers extracted various parameters for included trials, then cross-matched data with EU Clinical Trials Register, Clinical trials.gov, trial protocols (when available), and Google. The reporting of PRO data was then assessed for those Closed/Completed trials that included a PRO via PubMed/MEDLINE, Sponsor, and Google. Results: A sample of 664 CAR-T trials was identified. PROs were included in only 6.17% (41/664) studies. Of the 41 trials that included a PRO, 63.41% (26/41) utilized more than one PRO, with the generic EORTC QLQ-C30 and the EQ-5D being used predominately. Median HRQoL follow-up was 5-years on most trials. No studies used PROs as primary endpoints. The majority of PROs were observed to be utilized in early phase trials (phase I, 12; Phase I/II, 17). PROs were first incorporated in CAR-T trials beginning in 2014, and the utilization rate has increased steadily, except for 2019. PROs were included in 3 first line trials, 22 second line, 5 third line, and 11 fourth line or greater. PRO utilization between solid tumor trials and hematologic malignancies was comparable (6.04% [9/149], and 6.26% [32/511]). Of the completed/closed trials, 28.57% (3/14) published PRO data and met at least eight of the CONSORT-PRO quality indicators. Conclusions: The utilization of PROs in CAR-T trials (6.17%) is under the industry average of 27%, despite the growing importance of HRQoL and its impact on value-based care. The findings from this review reflect the overall increased attention to CAR-T as a new therapeutic entity and the continued deficiency of including and reporting of PROs in trial designs.

scholarly journals Potential of patient-reported outcomes as nonprimary endpoints in clinical trials

2013 ◽  
Vol 11 (1) ◽  
pp. 83 ◽  
Author(s):  
Ari Gnanasakthy ◽  
Sandra Lewis ◽  
Marci Clark ◽  
Margaret Mordin ◽  
Carla DeMuro
Keyword(s):  
Clinical Trials ◽  
Patient Reported Outcomes ◽  
Patient Reported

scholarly journals SAT0121 PAIN AND OTHER PATIENT-REPORTED OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO DID OR DID NOT ACHIEVE TREATMENT RESPONSE BASED ON IMPROVEMENT IN SWOLLEN JOINTS IN TOCILIZUMAB CLINICAL TRIALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 994.2-995
Author(s):  
A. Sebba ◽  
J. Han ◽  
S. Mohan
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Pain Score ◽  
Patient Reported Outcomes ◽  
Component Score ◽  
Link Type ◽  
Pain Scores ◽  
Sf 36 ◽  
Patient Reported ◽  
Nonresponder Group

Background:Significant improvements in pain and other patient-reported outcomes (PROs) have been shown in large clinical trials in patients with rheumatoid arthritis (RA) who receive tocilizumab (TCZ) compared with placebo (PBO). Recent data suggest that pain in RA may be noninflammatory as well as inflammatory, and improvement in pain scores and other PROs may be seen in patients who do not respond to treatment based on disease activity measures that evaluate inflammation.Objectives:To assess changes in pain scores and other PROs in patients with RA who did or did not achieve ≥ 20% improvement in SJC in TCZ clinical trials.Methods:Data from patients with active RA who received intravenous TCZ 8 mg/kg + MTX or PBO + MTX in 3 Phase III studies (OPTION [NCT00106548], TOWARD [NCT00106574] and LITHE [NCT00109408]) were included. All patients had moderate to severe RA with an inadequate response or intolerance of MTX (OPTION, LITHE) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; TOWARD). Changes in pain (visual analog scale [VAS], 0-100 mm), Health Assessment Questionnaire Disability Index (HAQ-DI, 0-3), 36-Item Short Form Survey (SF-36) physical component score (PCS) and mental component score (MCS; 0-50) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score (0-52) from baseline to Week 24 were evaluated. Results were compared between patients receiving TCZ + MTX and those receiving PBO + MTX in both patients who achieved ≥ 20% improvement in SJC (responders) and those who did not (nonresponders). The changes from baseline were analyzed using a mixed model with repeated measures, including the following covariates and interactions: treatment, visit, baseline of endpoint, region, baseline DAS28 and interactions of visit with treatment and baseline of endpoint.Results:Data from 1254 responders (TCZ + MTX, n = 831; PBO + MTX, n = 423) and 620 nonresponders (TCZ + MTX, n = 225; PBO + MTX, n = 395) were included. Patients receiving TCZ + MTX had significantly greater improvement in pain scores and HAQ-DI compared with PBO + MTX in the responder group (–27.19 vs –16.77 and –0.55 vs –0.34, respectively;P< 0.0001 for both) and nonresponder group (–9.59 vs 2.53 and –0.20 vs 0.01;P< 0.0001 for both) at Week 24 (Figure 1). Similar results were seen at Week 16 in the nonresponder group (–11.06 vs –2.38 and –0.23 vs –0.04;P< 0.0001 for both) prior to initiation of rescue treatment. At Week 24 in the responder group, patients receiving TCZ + MTX had significantly greater improvements compared with PBO + MTX in SF-36 PCS and MCS (9.16 vs 5.71 and 6.55 vs 3.79, respectively;P< 0.0001 for both) (Figure 2) and FACIT-Fatigue (8.39 vs 5.11;P< 0.0001). In the nonresponder group, patients receiving TCZ + MTX had significantly greater improvements compared with PBO + MTX in SF-36 PCS at Week 16 (3.81 vs 1.65;P= 0.0006) and Week 24 (4.42 vs 1.01;P< 0.0001) (Figure 2) and FACIT-Fatigue at Week 16 (3.82 vs 1.32;P= 0.0039) and Week 24 (3.90 vs 1.40;P= 0.0111).Conclusion:Patients with RA who received TCZ + MTX had significantly greater improvements in pain score and other PROs than those who received PBO + MTX regardless of whether they achieved ≥ 20% improvement in SJC. Clinical outcome at Week 24 correlated well with PROs, with a relatively larger improvement in pain score and other PROs in the responder group than in the nonresponder group; relative to PBO + MTX, these improvements appear numerically similar in the responder and nonresponder groups with consistently smaller difference between the groups in TCZ-treated arms. The consistent effect of TCZ on PROs in both responder and nonresponder groups warrants further study on the impact of TCZ on sources of pain independent of that caused by joint inflammation.Figure:Acknowledgments:This study was sponsored by Genentech, Inc. Support for third-party writing assistance, furnished by Health Interactions, Inc, was provided by Genentech, Inc.Disclosure of Interests:Anthony Sebba Consultant of: Genentech, Gilead, Lilly, Regeneron Pharmaceuticals Inc., Sanofi, Speakers bureau: Lilly, Roche, Sanofi, Jian Han Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Shalini Mohan Shareholder of: Genentech, Inc., Employee of: Genentech, Inc.

scholarly journals Longitudinal Analysis of Patient-Reported Outcomes in Clinical Trials: Applications of Multilevel and Multidimensional Item Response Theory

Psychometrika ◽  
2021 ◽  
Author(s):  
Li Cai ◽  
Carrie R. Houts
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Latent Variable ◽  
Patient Reported Outcomes ◽  
Multilevel Models ◽  
Latent Variable Models ◽  
Trial Data ◽  
Regulatory Science ◽  
Measurement Information ◽  
Patient Reported

AbstractWith decades of advance research and recent developments in the drug and medical device regulatory approval process, patient-reported outcomes (PROs) are becoming increasingly important in clinical trials. While clinical trial analyses typically treat scores from PROs as observed variables, the potential to use latent variable models when analyzing patient responses in clinical trial data presents novel opportunities for both psychometrics and regulatory science. An accessible overview of analyses commonly used to analyze longitudinal trial data and statistical models familiar in both psychometrics and biometrics, such as growth models, multilevel models, and latent variable models, is provided to call attention to connections and common themes among these models that have found use across many research areas. Additionally, examples using empirical data from a randomized clinical trial provide concrete demonstrations of the implementation of these models. The increasing availability of high-quality, psychometrically rigorous assessment instruments in clinical trials, of which the Patient-Reported Outcomes Measurement Information System (PROMIS®) is a prominent example, provides rare possibilities for psychometrics to help improve the statistical tools used in regulatory science.

Overview of the Patient Perspective at OMERACT 10 — Conceptualizing Methods for Developing Patient-Reported Outcomes

2011 ◽  
Vol 38 (8) ◽  
pp. 1699-1701 ◽  
Author(s):  
JOHN R. KIRWAN ◽  
PETER S. TUGWELL
Keyword(s):  
Clinical Trials ◽  
Experimental Work ◽  
Patient Reported Outcomes ◽  
Patient Perspective ◽  
Methodological Issues ◽  
Instrument Selection ◽  
Patient Reported ◽  
The Impact ◽  
Choice Of Instruments ◽  
The Way

This overview draws out the main conclusions from the 4 workshops focused on incorporating the patient perspective into outcome assessment at the 10th Outcome Measures in Rheumatology (OMERACT 10) conference. They raised methodological issues about the choice of outcome domains to include in clinical trials, the development or choice of instruments to measure these domains, and the way these instruments might capture the impact of a disease and its treatment. The need to develop a more rigorous conceptual model of quantifying the way conditions affect health, and the need to ensure patients are directly involved in the decisions about domains and instruments, emerged clearly. The OMERACT participants voted to develop guidelines for domain and instrument selection, and conceptual and experimental work will be brought forward to revise and upgrade the OMERACT Filter.

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