Empowering Healthcare with Real-World Evidence

Dive into our repository of groundbreaking research papers, where we merge clinical expertise with data driven insights to revolutionize patient care and treatment strategies.

Group 79
Merola D, Campbell U, Lenis D, Madsen A, Schneeweiss S, Wang S, Carrigan G, Taylor A, Huang J, Chia VM, Ovbiosa O, Pinheiro S, Pace ND, Bruno A, Stewart M, Khosla S, Zhang Y, Rimawi M, Hendricks-Sturrup R, Locke T, Jiao X, Becnel L, McRoy L, Rabon-Stith K, Eckert JC, Rodriguez-Watson C, Lunacsek O, Harvey R, Greshock J, Sarsour K, Belli A, Wang C, Fernandes L, Chen J, Natanzon Y, Dhopeshwarkar N, Wasserman A, Quinn J, Taylor B, Rider J
As a pilot exercise to assess feasibility of using routine clinical practice data to duplicate randomized control trial (RCT) design, we attempted to emulate the KEYNOTE-189 RCT using real-world data (RWD), and report findings from comparing the results.
Liliya Sinyavskaya, Aster Meche, Ariane Faucher, Patrick Hlavacek, Sarasa M. A. Johnson, Marco DiBonaventura, Francis Vekeman, Jinma Ren, Alex Schepart
Patients with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognoses. This high unmet need has prompted the development of new therapies allowing for improved outcomes for these patients. Recently, new targeted therapies for the treatment of patients with relapsed or refractory MM have been approved based on single-arm clinical trial results. Real-world (RW) data enable a better understanding of the effectiveness of new therapies in clinical practice and provide external controls for single-arm studies. However, using RW data to identify patients with TCR MM is challenging and subject to limitations.
Helmneh M. Sineshaw, Christina M. Zettler, Jennifer Prescott, Mahek Garg, Samhita Chakraborty, Eric M. Sarpong, Claire Bai, Andrew J. Belli, Laura L. Fernandes, Ching-Kun Wang
Although initial treatment of diffuse large B-cell lymphoma (DLBCL) with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) can be effective, up to 50% of patients will develop refractory or relapsed (R/R) disease. This study aimed to provide contemporary data on characteristics, treatment patterns, and outcomes for R/R-DLBCL.
Elizabeth D. Pulte; Laura L. Fernandes; Joseph Wynne; Eric Hansen; Andrew J. Belli; Anna Barcellos; Christina M. Zettler; Rebecca Bystrom; Jonathon Vallejo; Wenjuan Gu; Catherine Lerro; Kelly Norsworthy; Angelo DeClaro; Marc R. Theoret; Donna Rivera; Ching-Kun Wang
Treatment options for patients with acute myeloid leukemia (AML) have expanded in recent years. Although new treatments have demonstrated efficacy in clinical trials, less is known about their effect on outcomes in routine clinical practice. We examined outcomes for patients with newly-diagnosed AML (ND-AML) using real world data (RWD).
Benjamin A. Derman, Jacob Ambrose, Laura L. Fernandes, Christina M. Zettler, Eric Hansen, Andrew J. Belli, Ching-Kun Wang
Daratumumab (dara)-based triplet therapies are commonly used in the second-line (2L) and third-line (3L) settings in relapsed/refractory multiple myeloma (RRMM), usually in combination with dexamethasone and either bortezomib (dara-Vd), carfilzomib (dara-Kd), or pomalidomide (dara-Pd). We performed a real-world (rw) analysis to directly compare these regimens, to our knowledge, for the first time. This was an observational, retrospective cohort study using COTA’s rw database of patients with MM who have initiated 2L or 3L therapy with dara-Vd, dara-Kd, or dara-Pd. rw time to next treatment (rwTTNT) and rw overall survival (rwOS) were analyzed using the Kaplan-Meier method. Comparative analyses were conducted using a trimmed inverse probability of treatment weighting method to control for potential confounders. A total of 639 patients received a dara-based regimen as either 2L or 3L therapy (dara-Vd, n = 201; dara-Kd, n = 122; and dara-Pd, n = 316). A high proportion had functional (52%) or cytogenetic (26%) high-risk disease; 49% were lenalidomide refractory. Median rwTTNT for dara-Vd was 7.6 months and was 12.9 months for dara-Kd (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.49-0.99). Similarly, median rwTTNT for dara-Vd was 6.9 months and 15.3 months for dara-Pd (HR, 0.57; 95% CI, 0.43-0.77). Median rwTTNT for dara-Pd was 15.7 months, and for dara-Kd 13.2 months (HR, 1.1; 95% CI, 0.8-1.6). No regimen was associated with superior rwOS. Among patients with RRMM receiving 2L or 3L therapy with a dara-based triplet, dara-Vd was associated with inferior rwTTNT compared with both dara-Kd and dara-Pd. dara-Vd may not be a suitable control arm for most phase 3 studies.
Luciano J Costa, Thomas W LeBlanc, Hans Tesch, Pieter Sonneveld, Ryan P Kyle, Liliya Sinyavskaya, Patrick Hlavacek, Aster Meche, Jinma Ren, Alex Schepart, Didem Aydin, Guido Nador, Marco daCosta DiBonaventura
Elranatamab efficacy in the single-arm, registrational MagnetisMM-3 trial (NCT04649359) was compared with that of physician’s choice of treatment (PCT) for triple-class refractory multiple myeloma. MagnestisMM-3 eligibility criteria were applied to two USA-based oncology electronic health record databases, COTA and Flatiron Health (FH), to identify cohorts for this study (NCT05932290). Applied statistical techniques accounted for cohort imbalances. MagnetisMM-3 (BCMA-naive; n = 123) outcomes were compared with those from COTA (n = 239) and FH (n = 152). Elranatamab was associated with a significantly higher objective response rate (risk ratios, 1.88–2.25), significantly longer progression-free survival (hazard ratios [HRs], 0.37–0.57), and, across most analyses, significantly longer overall survival (HRs, 0.46–0.66) versus PCT. BCMA-naive patients who were treated with elranatamab exhibited significantly better outcomes than patients treated in real-world clinical practice.
Andrew Ip, Alex Mutebi, Tongsheng Wang, Monika Jun, Anupama Kalsekar, Fernando Rivas Navarro, Anthony Wang, Rajesh Kamalakar, Mariana Sacchi, Brian Elliott
Despite new therapies for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), treatments with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents continue to be commonly used.
K. Parikh, K. Leventakos, A.S. Mansfield, A. Dimou, J.R. Molina, J. Ambrose, C. Bai, E. Hansen, A. Barcellos, C. Zettler, A. Belli, L. Fernandes, C.K. Wang
While metastatic NSCLC (mNSCLC) with high PDL1 expression (≥50%) can be treated with single-agent immune-checkpoint inhibitors (ICI) or combination chemoimmunotherapy, there are no prospective comparisons between these strategies. We analyzed the real-world comparative effectiveness of frontline ICI versus ICI+chemotherapy (chemo) among patients with mNSCLC with ≥50% PD-L1 expression and without EGFR, ALK, or ROS1 alterations.
Rahul Dhanda, Ching-Kun Wang, Andrew J Belli
The fit-for-use of RWD including data quality and provenance are critical components that will aid the Federal Drug Administration (FDA) to assess the adequacy of RWE (Real World Evidence) to support it on the regulatory pathway. We review the best practice in the curation and use of Real World data in support of RWE submissions to the FDA.
Matthew S. Davids MD MMSc, Jacob Ambrose MS, Enrico De Nigris MSc, Jennifer Prescott, Siyang Leng MD MS, Mohammed Z.H. Farooqui DO, Shravanthi R. Gandra PhD MBA, Christina M. Zettler, Laura L. Fernandes PhD, Ching-Kun Wang MD, Mazyar Shadman MD MPH
Bruton’s Tyrosine Kinase inhibitors (BTKis) and B-cell lymphoma 2 inhibitors (BCL2is) are targeted agents that have proven to be particularly effective in treating chronic lymphocytic leukemia (CLL). It is critical to understand the current utilization patterns and outcomes of patients receiving these therapies in a sequential manner in the real-world (rw). This study explored patient characteristics and treatment outcomes for patients who were exposed to and discontinued treatment with BTKis and BCL2is in two consecutive lines of therapy (LOTs) for CLL.