Frailty impairs the feasibility of induction therapy but not of maintenance therapy in elderly myeloma patients: final results of the German Maintenance Study (GERMAIN)

J Cancer Res Clin Oncol. 2020 Mar;146(3):749-759. doi: 10.1007/s00432-019-03101-z. Epub 2019 Dec 2.

Abstract

Purpose: The German Maintenance Study (GERMAIN) was designed to evaluate the impact of lenalidomide maintenance after induction therapy with bortezomib, melphalan and prednisolone (VMP) in transplant-ineligible newly diagnosed multiple myeloma (MM) patients.

Methods: Due to poor accrual and high dropout rate, only 85 patients (planned 286) entered the trial and 40 (planned 200) were randomized to lenalidomide maintenance (n = 19) vs. observation (n = 21).

Results: The primary endpoint, improved progression-free survival, was not met (p = 0.3572). After a median follow-up of 12.9 months, median progression-free survival in the lenalidomide arm was 14.4 months and 11.4 months with placebo. The hazard ratio 0.621 (95% confidence interval: [0.224, 1.725]) was about the same as expected (0.625). However, with only 40 patients randomized, the actual power to detect a difference was 11%. Of patients receiving at least one dose of induction, 54% were frail according to a modified International Myeloma Working Group frailty score. Discontinuations were high during induction (47%), and affected mainly frail patients (54%). Despite a higher rate of adverse events in the lenalidomide arm (p = 0.0061), only 2 patients discontinued lenalidomide due to toxicity.

Conclusion: A frailty assessment with appropriate dose modification for induction therapy should be mandatory for all elderly non-transplant-eligible myeloma patients.

Keywords: Frailty score; Maintenance; Multiple myeloma; Transplant-ineligible patients.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bortezomib / therapeutic use
  • Double-Blind Method
  • Female
  • Frail Elderly
  • Frailty*
  • Humans
  • Induction Chemotherapy / adverse effects
  • Induction Chemotherapy / methods*
  • Lenalidomide / therapeutic use*
  • Maintenance Chemotherapy / methods*
  • Male
  • Melphalan / therapeutic use
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Prednisolone / therapeutic use
  • Progression-Free Survival

Substances

  • Bortezomib
  • Prednisolone
  • Lenalidomide
  • Melphalan

Grants and funding