Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 1b study from GELTAMO group

Br J Haematol. 2016 Apr;173(2):245-52. doi: 10.1111/bjh.13945. Epub 2016 Feb 5.

Abstract

Diffuse large B-cell lymphoma (DLBCL) patients failing rituximab-containing therapy have a poor outcome with the current salvage regimens. We conducted a phase 1b trial to determine the maximum tolerated dose (MTD) of lenalidomide in combination with R-ESHAP (rituximab, etoposide, cisplatin, cytarabine, methylprednisolone) (LR-ESHAP) in patients with relapsed or refractory DLBCL. Efficacy data were collected as a secondary objective. Subjects received 3 cycles of lenalidomide at escalating doses (5, 10 or 15 mg) given on days 1-14 of every 21-day cycle, in combination with R-ESHAP. Responding patients received BEAM (carmustine, etoposide, cytarabine, melphalan) followed by autologous stem-cell transplantation. Lenalidomide 10 mg/d was identified as the MTD because, in the 15 mg cohort, one patient experienced dose-limiting toxicity (grade 3 angioedema) and two patients had mobilization failure. A total of 19 patients (3, 12 and 4 in the 5, 10 and 15 mg cohorts, respectively) were evaluable. All toxicities occurring during LR-ESHAP cycles resolved appropriately and no grade 4-5 non-haematological toxicities were observed. The complete remission and overall response rates were 47·4% and 78·9%, respectively. With a median follow-up of 24·6 (17·4-38·2) months, the 2-year progression-free survival and overall survival were 44% and 63%, respectively. In conclusion, the LR-ESHAP regimen is feasible and yields encouraging outcomes.

Keywords: R-ESHAP; diffuse large B-cell lymphoma; lenalidomide; rituximab; salvage.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chronic Disease
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Dose-Response Relationship, Drug
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Humans
  • Lenalidomide
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Remission Induction / methods
  • Salvage Therapy / methods
  • Thalidomide / administration & dosage
  • Thalidomide / adverse effects
  • Thalidomide / analogs & derivatives
  • Treatment Outcome
  • Young Adult

Substances

  • Cytarabine
  • Thalidomide
  • Etoposide
  • Lenalidomide
  • Cisplatin
  • Prednisone

Supplementary concepts

  • ESHAP regimen