RB but not R-HCVAD is a feasible induction regimen prior to auto-HCT in frontline MCL: results of SWOG Study S1106

Br J Haematol. 2017 Mar;176(5):759-769. doi: 10.1111/bjh.14480. Epub 2016 Dec 19.

Abstract

Aggressive induction chemotherapy followed by autologous haematopoietic stem cell transplant (auto-HCT) is effective for younger patients with mantle cell lymphoma (MCL). However, the optimal induction regimen is widely debated. The Southwestern Oncology Group S1106 trial was designed to assess rituximab plus hyperCVAD/MTX/ARAC (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone, alternating with high dose cytarabine and methotrexate) (RH) versus rituximab plus bendamustine (RB) in a randomized phase II trial to select a pre-transplant induction regimen for future development. Patients had previously untreated stage III, IV, or bulky stage II MCL and received either 4 cycles of RH or 6 cycles of RB, followed by auto-HCT. Fifty-three of a planned 160 patients were accrued; an unacceptably high mobilization failure rate (29%) on the RH arm prompted premature study closure. The estimated 2-year progression-free survival (PFS) was 81% vs. 82% and overall survival (OS) was 87% vs. 88% for RB and RH, respectively. RH is not an ideal platform for future multi-centre transplant trials in MCL. RB achieved a 2-year PFS of 81% and a 78% MRD negative rate. Premature closure of the study limited the sample size and the precision of PFS estimates and MRD rates. However, RB can achieve a deep remission and could be a platform for future trials in MCL.

Keywords: MRD; Auto-HCT; bendamustine; hyperCVAD; mantle cell.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bendamustine Hydrochloride / administration & dosage*
  • Combined Modality Therapy / methods
  • Combined Modality Therapy / mortality
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Dexamethasone / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Lymphoma, Mantle-Cell / mortality
  • Lymphoma, Mantle-Cell / therapy*
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Neoplasm, Residual / diagnosis
  • Remission Induction / methods*
  • Rituximab / administration & dosage*
  • Transplantation, Autologous
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Young Adult

Substances

  • Cytarabine
  • Rituximab
  • Vincristine
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Bendamustine Hydrochloride
  • Methotrexate

Supplementary concepts

  • CVAD protocol