Analysis of Common Eligibility Criteria of Randomized Controlled Trials in Newly Diagnosed Multiple Myeloma Patients and Extrapolating Outcomes

Clin Lymphoma Myeloma Leuk. 2017 Sep;17(9):575-583.e2. doi: 10.1016/j.clml.2017.06.013. Epub 2017 Jun 17.

Abstract

Background: The performance of multiple myeloma (MM) therapies in a general patient population and specific eligibility criteria that might limit enrollment into randomized controlled trials (RCTs) have not been evaluated in depth. This study aimed to determine if improvements seen with MM therapies in RCTs are reflected in the general patient population and to identify eligibility criteria that can be modified to increase enrollment.

Patients and methods: The Connect MM Registry is a prospective observational cohort study of patients with newly diagnosed MM (NDMM) in the United States. Using common RCT exclusion criteria collected from 16 published studies, patients in the registry were categorized according to their eligibility for inclusion in RCTs.

Results: On the basis of common criteria, 563 of 1406 of registry patients (40.0%) are ineligible for RCTs. Criteria leading to exclusion included M-protein ≤ 1.0 g/dL (25.2%), creatinine > 2.5 mg/dL (13.9%), low absolute neutrophil count (10.0%), and low hemoglobin (9.6%). Significantly more RCT-ineligible versus RCT-eligible patients had hypercalcemia (11.0% vs. 5.5%), elevated creatinine levels (38.9% vs. 6.2%), low hemoglobin levels (59.5% vs. 39.5%), or International Staging System stage III disease (40.1% vs. 22.1%; P < .001 for all comparisons). RCT-ineligible patients had a lower 3-year survival rate than RCT-eligible patients (63% vs. 70%). The incidence of serious adverse events was similar between groups.

Conclusion: Of patients with NDMM enrolled in the Connect MM Registry, 40% are ineligible for RCTs. This study provides insight into potential modifications of standard eligibility criteria that can lead to improved RCT design and accelerated enrollment.

Keywords: Baseline disease characteristics; Clinical trial design; Community practice; Connect MM registry; NDMM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Female
  • Guideline Adherence
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / epidemiology*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy
  • Neoplasm Staging
  • Randomized Controlled Trials as Topic*
  • Registries
  • Research Design*
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers