Impact of renal impairment on outcomes with lenalidomide and dexamethasone treatment in the FIRST trial, a randomized, open-label phase 3 trial in transplant-ineligible patients with multiple myeloma

Haematologica. 2016 Mar;101(3):363-70. doi: 10.3324/haematol.2015.133629. Epub 2015 Dec 11.


Renal impairment is associated with poor prognosis in myeloma. This analysis of the pivotal phase 3 FIRST trial examined the impact of renally adapted dosing of lenalidomide and dexamethasone on outcomes of patients with different degrees of renal impairment. Transplant-ineligible patients not requiring dialysis were randomized 1:1:1 to receive continuous lenalidomide and dexamethasone until disease progression (n=535) or for 18 cycles (72 weeks; n=541), or melphalan, prednisone, and thalidomide for 12 cycles (72 weeks; n=547). Follow-up is ongoing. Patients were grouped by baseline creatinine clearance into no (≥ 80 mL/min [n=389]), mild (≥ 50 to < 80 mL/min [n=715]), moderate (≥ 30 to < 50 mL/min [n=372]), and severe impairment (< 30 mL/min [n=147]) subgroups. Continuous lenalidomide and dexamethasone therapy reduced the risk of progression or death in no, mild, and moderate renal impairment subgroups vs. melphalan, prednisone, and thalidomide therapy (HR = 0.67, 0.70, and 0.65, respectively). Overall survival benefits were observed with continuous lenalidomide and dexamethasone treatment vs. melphalan, prednisone, and thalidomide treatment in no or mild renal impairment subgroups. Renal function improved from baseline in 52.6% of lenalidomide and dexamethasone-treated patients. The safety profile of continuous lenalidomide and dexamethasone was consistent across renal subgroups, except for grade 3/4 anemia and rash, which increased with increasing severity of renal impairment. Continuous lenalidomide and dexamethasone treatment, with renally adapted lenalidomide dosing, was effective for most transplant-ineligible patients with myeloma and renal impairment. Trial registration: (NCT00689936); EudraCT (2007-004823-39). Funding: Intergroupe Francophone du Myélome and the Celgene Corporation.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Creatinine / blood
  • Dexamethasone / therapeutic use*
  • Disease Progression
  • Drug Administration Schedule
  • Female
  • Humans
  • Lenalidomide
  • Male
  • Melphalan / therapeutic use
  • Middle Aged
  • Multiple Myeloma / complications
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Prednisone / therapeutic use
  • Prognosis
  • Prospective Studies
  • Renal Insufficiency / complications
  • Renal Insufficiency / diagnosis
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency / mortality
  • Severity of Illness Index
  • Survival Analysis
  • Thalidomide / analogs & derivatives*
  • Thalidomide / therapeutic use
  • Treatment Outcome


  • Thalidomide
  • Dexamethasone
  • Creatinine
  • Lenalidomide
  • Melphalan
  • Prednisone

Associated data

  • EudraCT/2007-004823-39