Subsequent primary malignancies and acute myelogenous leukemia transformation among myelodysplastic syndrome patients treated with or without lenalidomide

Cancer Med. 2016 Jul;5(7):1694-701. doi: 10.1002/cam4.721. Epub 2016 Apr 20.

Abstract

The few studies that have examined rates of acute myeloid leukemia (AML) transformation in lenalidomide-treated myelodysplastic syndrome (MDS) patients have been limited to deletion 5q MDS. The association between lenalidomide and subsequent primary malignancies (SPMs) in MDS patients has not been evaluated previously. We conducted a retrospective cohort study to evaluate the risk of both SPM and AML in association with lenalidomide. A cohort of MDS patients (n = 1248) treated between 2004 and 2012 at Moffitt Cancer Center were identified, and incident cases of SPM and AML transformation were ascertained. Using a nested case-control design, MDS controls were 1:1 matched to SPM (n = 41) and AML (n = 150) cases, on age and date of MDS diagnosis, gender, follow-up time, IPSS, and del (5q). Associations between lenalidomide and (1) SPM incidence and (2) AML transformation were estimated with hazards ratios (HR) and 95% confidence intervals (CIs) in the cohort and odds ratios (OR) in the case-control analysis. SPM incidence did not differ significantly between cohort MDS patients treated with (0.7 per 100 person-years) or without lenalidomide (1.4 per 100 person-years) (HR = 1.04, 95% CI = 0.40-2.74), whereas a significantly reduced SPM risk was observed in the case-control sample (OR = 0.03, 95% CI = <0.01-0.63). Lenalidomide was not associated with AML transformation in the cohort analysis (HR = 0.75, 95% CI = 0.44-1.27) or in the case-control analyses (OR = 1.16, 95% CI = 0.52-2.56), after adjustment for potential confounders. Lenalidomide was not associated with increased risk of SPM or AML transformation in a large cohort of MDS patients mostly including nondeletion 5q MDS.

Keywords: Acute myelogenous leukemia; lenalidomide; myelodysplastic syndrome; subsequent primary malignancies.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Case-Control Studies
  • Cell Transformation, Neoplastic*
  • Cohort Studies
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Lenalidomide
  • Leukemia, Myeloid, Acute / epidemiology
  • Leukemia, Myeloid, Acute / etiology*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / epidemiology
  • Myelodysplastic Syndromes / mortality
  • Myelodysplastic Syndromes / pathology*
  • Neoplasms, Second Primary / epidemiology
  • Neoplasms, Second Primary / etiology*
  • Neoplasms, Second Primary / mortality
  • Registries
  • Retrospective Studies
  • Risk Factors
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives

Substances

  • Thalidomide
  • Lenalidomide