The use of novel drugs can effectively improve response, delay relapse and enhance overall survival in multiple myeloma patients with renal impairment

PLoS One. 2014 Jul 8;9(7):e101819. doi: 10.1371/journal.pone.0101819. eCollection 2014.

Abstract

Background: Renal impairment is a common feature in multiple myeloma and is considered a poor prognostic factor.

Aim: To determine the impact of novel drugs (i.e. bortezomib, lenalidomide and thalidomide) in the treatment of myeloma patients with renal impairment. The primary endpoint was overall survival and secondary endpoints were time to next treatment and response.

Methods: The study population included all patients diagnosed with treatment-demanding multiple myeloma January 2000 to June 2011 at 15 Swedish hospitals. Renal impairment was defined as an estimated glomerular filtration rate under 60 mL/min/1.73 m2.

Result: The study population consisted of 1538 patients, of which 680 had renal impairment at diagnosis. The median overall survival in patients with renal impairment was 33 months, which was significantly shorter than 52 months in patients with normal renal function (P<0.001). Novel agents in first line improved overall survival (median 60 months) in non-high-dose treated patients with renal impairment (n = 143) as compared to those treated with conventional cytotoxic drugs (n = 411) (median 27 months) (P<0.001). In the multivariate analysis up front treatment with bortezomib was an independent factor for better overall survival in non-high-dose treated renally impaired patients. High-dose treated renally impaired patients had significantly better median overall survival than non-high-dose ones (74 versus 26 months) and novel drugs did not significantly improve survival further in these patients. Patients with renal impairment had both a shorter median time to next treatment and a lower response rate than those with normal renal function. However, novel drugs and high dose treatment lead to a significantly longer time to next treatment and the use of novel agents significantly improved the response rate of these patients.

Conclusion: High dose treatment and novel drugs, especially bortezomib, can effectively overcome the negative impact of renal impairment in patients with multiple myeloma.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Male
  • Middle Aged
  • Mortality
  • Multiple Myeloma / complications*
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / epidemiology*
  • Multiple Myeloma / mortality
  • Neoplasm Recurrence, Local
  • Registries
  • Renal Insufficiency / etiology*
  • Renal Insufficiency / physiopathology
  • Retreatment
  • Sweden / epidemiology
  • Treatment Outcome

Grants and funding

Swedish cancer society, Swedish Research Council, Cancer Foundation in Sweden, Janssen-Cilag AB, Celgene lifetime achievement award. The funder provided support in the form of salaries for authors Johan Liwing and Johan Aschan, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.