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Evaluation of Minimal Residual Disease as a Surrogate for Progression-Free Survival in Hematology Oncology Trials: A Meta-Analytic Review

Jane She, Xiaofei Chen, Malini Iyengar, Judy Li

TL;DR

This work examines individual-level and trial-level correlations extracted from previously published studies to elucidate the potential role of MRD in accelerating the drug approval process in hematology oncology trials.

Abstract

Traditional health authority approval for oncology drugs is based on a clinical benefit endpoint, or a valid surrogate. In 1992 the FDA created the Accelerated Approval pathway to allow for earlier approval of therapies in serious conditions with an unmet medical need. This is accomplished typically by granting accelerated approval based on a surrogate endpoint that can be measured earlier than a traditional approval endpoint. Minimal residual disease (MRD) is a sensitive measure of residual cancer cells in hematology oncology after treatment, and is increasingly considered as a secondary or exploratory endpoint due to its prognostic potential for traditional clinical trial endpoints such as progression-free survival (PFS) and overall survival (OS). This work aims to evaluate MRD's surrogacy potential across several hematologic cancer indications while keeping the focus on follicular lymphoma (FL), using data from published studies. We examine individual-level and trial-level correlations extracted from previously published studies to elucidate the potential role of MRD in accelerating the drug approval process in hematology oncology trials.

Evaluation of Minimal Residual Disease as a Surrogate for Progression-Free Survival in Hematology Oncology Trials: A Meta-Analytic Review

TL;DR

This work examines individual-level and trial-level correlations extracted from previously published studies to elucidate the potential role of MRD in accelerating the drug approval process in hematology oncology trials.

Abstract

Traditional health authority approval for oncology drugs is based on a clinical benefit endpoint, or a valid surrogate. In 1992 the FDA created the Accelerated Approval pathway to allow for earlier approval of therapies in serious conditions with an unmet medical need. This is accomplished typically by granting accelerated approval based on a surrogate endpoint that can be measured earlier than a traditional approval endpoint. Minimal residual disease (MRD) is a sensitive measure of residual cancer cells in hematology oncology after treatment, and is increasingly considered as a secondary or exploratory endpoint due to its prognostic potential for traditional clinical trial endpoints such as progression-free survival (PFS) and overall survival (OS). This work aims to evaluate MRD's surrogacy potential across several hematologic cancer indications while keeping the focus on follicular lymphoma (FL), using data from published studies. We examine individual-level and trial-level correlations extracted from previously published studies to elucidate the potential role of MRD in accelerating the drug approval process in hematology oncology trials.
Paper Structure (13 sections, 5 figures, 5 tables)

This paper contains 13 sections, 5 figures, 5 tables.

Table of Contents

  1. Introduction
  2. Materials and Methods
  3. Literature Search & Review
  4. Data Extraction
  5. Evaluation of Surrogacy
  6. One-arm trials
  7. Results
  8. Discussion
  9. Conclusion
  10. Funding Statement
  11. Conflict of Interest
  12. Author Contributions
  13. Supplemental Material

Figures (5)

  • Figure 1: Flowchart for Surrrogacy Assessment
  • Figure 2: Weighted by inverse variance of log OR: Correlation between treatment effect on MRD negativity and treatment effect on PFS. (A) all points: WLS for FL with all points included; (B) sensitivity analysis: WLS for FL with FOLL12 excluded
  • Figure 3: Weighted by sample size: Correlation between treatment effect on MRD negativity and treatment effect on PFS. (A) all points: WLS for FL with all points included; (B) sensitivity analysis: WLS for FL with FOLL12 excluded
  • Figure 4: Correlation between treatment effect on MRD negativity and treatment effect on PFS; (A) weighted by the inverse variance of the log OR; (B) weighted by the sample size
  • Figure 5: Example Plot of Single Arm Correlation