Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: the Fondazione Italiana Linfomi MCL0208 trial

Blood Adv. 2023 Jul 25;7(14):3764-3774. doi: 10.1182/bloodadvances.2022009504.


In the Fondazione Italiana Linfomi MCL0208 phase 3 trial, lenalidomide maintenance (LEN) after autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL) improved progression-free survival (PFS) vs observation (OBS). The host pharmacogenetic background was analyzed to decipher whether single-nucleotide polymorphisms (SNPs) of genes encoding transmembrane transporters, metabolic enzymes, or cell-surface receptors might predict drug efficacy. Genotypes were obtained via real-time polymerase chain reaction of the peripheral blood germ line DNA. Polymorphisms of ABCB1 and VEGF were found in 69% and 79% of 278 patients, respectively, and predicted favorable PFS vs homozygous wild-type (WT) in the LEN arm was 3-year PFS of 85% vs 70% (P < .05) and 85% vs 60% (P < .01), respectively. Patients carrying both ABCB1 and VEGF WT had the poorest 3-year PFS (46%) and overall survival (76%); in fact, in these patients, LEN did not improve PFS vs OBS (3-year PFS, 44% vs 60%; P = .62). Moreover, the CRBN polymorphism (n = 28) was associated with lenalidomide dose reduction or discontinuation. Finally, ABCB1, NCF4, and GSTP1 polymorphisms predicted lower hematological toxicity during induction, whereas ABCB1 and CRBN polymorphisms predicted lower risk of grade ≥3 infections. This study demonstrates that specific SNPs represent candidate predictive biomarkers of immunochemotherapy toxicity and LEN efficacy after ASCT in MCL.

Publication types

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

MeSH terms

  • Adult
  • Biomarkers
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lenalidomide / therapeutic use
  • Lymphoma, Mantle-Cell* / drug therapy
  • Lymphoma, Mantle-Cell* / genetics
  • Transplantation, Autologous
  • Vascular Endothelial Growth Factor A


  • Biomarkers
  • Lenalidomide
  • Vascular Endothelial Growth Factor A