Should Overall Survival Remain an Endpoint for Multiple Myeloma Trials?

  • Sarah A. Holstein
  • Vera J. Suman
  • Philip L. McCarthyEmail author
Stem Cell Transplantation (R Maziarz, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Stem Cell Transplantation


Purpose of Review

While the traditional gold standard for demonstrating clinical benefit of a therapy has been to show prolongation of overall survival (OS), there are multiple factors which can hinder the use of OS as a primary endpoint in randomized clinical trials (RCTs). Here, we analyze recent myeloma RCTs and evaluate the issues relevant to current and future myeloma RCT design.

Recent Findings

A review of recent phase III RCTs that led to approval of new agents/combinations reveals that none were designed with OS as the primary endpoint, but instead utilized time to progression (TTP) or progression-free survival (PFS). These studies illuminate the inherent difficulties of designing trials with the primary endpoint of OS/PFS in a disease characterized by increasingly prolonged survival times, availability of effective salvage therapies, and competing events such as co-morbid conditions.


Alternative primary endpoints other than OS or PFS need to be developed for future myeloma RCTs. Validated surrogate endpoints with novel clinical trial designs will help improve the feasibility of conducting comparative clinical trials in a timely manner.


Multiple myeloma Overall survival Primary endpoint Clinical trial 


Compliance with Ethical Standards

Conflict of Interest

Sarah Holstein reports serving as an advisory board member for Celgene, Takeda, and Adaptive Biotechnologies and as a consultant for Celgene and GlaxoSmithKline, outside the submitted work. Vera Suman declares no potential conflicts of interest. Philip McCarthy reports receiving honoraria from Bristol-Myers Squibb, Celgene, Sanofi-Aventis, Takeda, and Binding Site and research funding from Celgene and has served on advisory committees/review panels/board membership for Bristol-Myers Squibb, Celgene, Sanofi-Aventis, Takeda, Binding Site, and Karyopharm outside the submitted work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Sarah A. Holstein
    • 1
  • Vera J. Suman
    • 2
  • Philip L. McCarthy
    • 3
    Email author
  1. 1.Department of Internal Medicine, Division of Oncology and HematologyUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of Health Sciences Research, Division of Biomedical Statistics and InformaticsMayo ClinicRochesterUSA
  3. 3.Department of Medicine, Blood and Marrow Transplant Center, Transplant and Cellular Therapy ProgramRoswell Park Comprehensive Cancer CenterBuffaloUSA

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