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3763 Design and Methodological Considerations for Real World Data-Derived Progression-Free Survival in Multiple Myeloma

Program: Oral and Poster Abstracts
Session: 907. Outcomes Research: Plasma Cell Disorders: Poster II
Hematology Disease Topics & Pathways:
Research, Epidemiology, Clinical Research, Health outcomes research, Real-world evidence
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Jocelyn R Wang1*, Jennifer Hayden1*, Yiyang Yue1*, Craig S Meyer1*, Ryan W Gan1*, Youyi Zhang1*, Benjamin Ackerman1*, Pranay Mohanty1*, James Roose2*, Jennifer L Lund3*, Sebastian Schneeweiss4*, Janick Weberpals4*, Omar Nadeem, MD5, Sikander Ailawadhi, MD6, Noopur Raje7, Smith Giri8*, Juned Siddique9*, Laura Hester10*, Kelly Reid1*, Robin Carson, MD11, Khaled Sarsour, PhD, MPH1* and Ashita Batavia, MD, MSc1*

1Janssen Research & Development, LLC, Titusville, NJ
2Flatiron Health, New York, NY
3Department of Epidemiology, University of North Carolina, Chapel Hill, Chapel Hill, NC
4Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
5Center for Early Detection and Interception of Blood Cancers, Dana-Farber Cancer Institute, Boston, MA
6Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL
7Massachusetts General Hospital, Boston, MA
8University of Alabama at Birmingham, Birmingham, AL
9Feinberg School of Medicine, Northwestern University, Chicago, IL
10Janssen Research & Development, LLC, Horsham, PA
11Janssen Research & Development, LLC, Spring House, PA

Introduction:

Progression-free survival (PFS), a common endpoint used in multiple myeloma (MM) trials, is defined as the time to the earliest occurrence of disease progression or death. Disease progression in MM is determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria based on imaging and biomarkers from blood, urine, and bone marrow biopsy testing. In clinical trials, IMWG-recommended assessments are protocol-based. However, in routine care, they are often performed and recorded differently based on a multitude of factors. Algorithms to ascertain progression events using routinely collected biomarker data are important to classify disease progression and align with trial-defined endpoints. The aim of this study was to construct and evaluate an optimized real-world Progression (rwP) algorithm using real-world data (RWD) and demonstrate how biomarker data are captured and used to derive endpoints in routine practice.

Method:

A cohort of 270 transplant ineligible newly diagnosed MM (NDMM) patients starting on lenalidomide and dexamethasone (Rd) and meeting select MAIA (NCT02252172) trial eligibility criteria were included from the nationwide Flatiron Health electronic health record-derived deidentified database from 2015 to 2023. A rwP algorithm was developed using key IMWG-recommended biomarkers, including serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and serum free light chains (FLCs).

The initial baseline value for each biomarker was identified, if available, during either the pre-treatment period (45 days prior through 7 days after first line treatment (1L) start) or the on-treatment period (8 days after 1L start through 1L end). Available biomarkers were followed for disease assessment. If any subsequent lab value during 1L treatment was less than the initial baseline value, the subsequent “on-treatment baseline” value was adopted as the new lowest value; otherwise, the initial value was used as the “on-treatment baseline” value for assessing progression events.

Three hierarchies, which describe the order of utilizing key IMWG-recommended biomarkers to define rwP events, were explored, including: i) strict hierarchy (SH) [SPEP > UPEP > FLCs], ii) partial hierarchy (PH) [SPEP = UPEP > FLCs], and iii) no hierarchy (NH) [SPEP = UPEP = FLCs]. The PH option closely resembles the IMWG criteria, with FLCs only used for rwP assessments when no measurable SPEP/UPEP are identified. The NH approach considers all available biomarkers equally and resembles how they are utilized in real-world clinical practice. The feasibility of requiring confirmatory events following the first suggestion of progression was also explored. Assays following the progression event up to the end of 1L were considered as confirmatory progression events if they met IMWG criteria.

Results:

We applied the rwP algorithm with each hierarchy to all eligible NDMM patients (N = 270). The SH, PH, and NH approaches respectively identified 106 (39.3%), 106 (39.3%), and 123 (45.6%) patients with progression events. Results from the SH and PH approach are consistent likely due to the rarity of UPEP usage in clinical practice. The NH approach captured more progression events because FLCs are used in the presence of measurable SPEP or UPEP, resulting in 73 progression events captured by FLCs in comparison to 32 from other approaches, potentially increasing false-positive capture due to the volatility of FLC results.

Among the 106 PH-identified patients who progressed, 84 (79.2%) had IMWG-recommended tests following their progression event, and 74 (69.8%) had their progression confirmed before the end of 1L, with 35 (33.0%) receiving their confirmatory reading within 2 months after progression. These results suggest that requiring confirmatory testing as part of the rwP is feasible, though it may introduce false negatives for patients receiving clinical progression confirmation instead of getting confirmatory labs in routine clinical practice.

Conclusion:

We present a comprehensive assessment of important design choices for an rwP algorithm for NDMM, including a hierarchy of key assays and the inclusion of confirmatory testing. Further validation of the algorithm with health care provider assessments and the inclusion of bone marrow biopsy and imaging data is important for evaluating the performance of the algorithm in RWD.

Disclosures: Wang: Johnson & Johnson Innovative Medicine: Current Employment; GlasoSmithKline: Other: Spouse's current employment; Aetion INC.: Current holder of stock options in a privately-held company. Hayden: Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company; Aetion Inc.: Current holder of stock options in a privately-held company. Yue: Janssen Research & Development, LLC: Ended employment in the past 24 months. Meyer: Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company. Gan: Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company. Zhang: Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company. Ackerman: Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company; Flatiron Health: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Mohanty: Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company. Roose: Flatiron Health: Current Employment; Roche Group: Current equity holder in publicly-traded company. Lund: F-Hoffman La Roche: Research Funding. Schneeweiss: Boehringer Ingelheim: Research Funding; Takeda: Research Funding; UCB: Research Funding; Aetion Inc.: Current equity holder in private company; Temedica GmbH: Other: Advisor. Weberpals: Boehringer Ingelheim: Other: Spouse's current employment. Nadeem: Pfizer: Honoraria; JNJ: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; GPCR Therapeutics: Membership on an entity's Board of Directors or advisory committees. Ailawadhi: Bristol-Myers Squibb: Consultancy, Research Funding; Abbvie: Research Funding; Xencor: Research Funding; Johnson and Johnson: Consultancy, Research Funding; Regeneron: Consultancy; Beigene: Consultancy; Ascentage: Research Funding; Takeda: Consultancy; BMS: Consultancy, Research Funding; Cellectar: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Pharmacuclics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy; GSK: Consultancy, Research Funding. Raje: Janssen Biotech Inc: Membership on an entity's Board of Directors or advisory committees; Caribou Biosciences Inc: Membership on an entity's Board of Directors or advisory committees; Onyx Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen Inc: Other: Steering Committee; Takeda Pharmaceuticals USA Inc: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Immuneel Therapeutics: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Roche Laboratories Inc: Other: Steering Committee. Giri: Janssen Research & Development, LLC: Honoraria, Research Funding, Speakers Bureau; Sanofi: Honoraria, Research Funding, Speakers Bureau. Hester: Johnson & Johnson Innovative Medicine: Current Employment; Johnson and Johnson: Current holder of stock options in a privately-held company; Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company. Reid: Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company. Carson: Janssen: Current Employment, Current holder of stock options in a privately-held company. Sarsour: Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company. Batavia: Johnson & Johnson Innovative Medicine: Current Employment.

*signifies non-member of ASH