title: RB but not R-HCVAD is a feasible induction regimen prior to auto-HCT in frontline MCL: results of SWOG Study S1106.
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.
authors.affiliation: City of Hope, Duarte, CA, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Chen
authors.affiliation: SWOG Statistical Center, Seattle, WA, USA.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.affiliation: James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Bernstein
authors.affiliation: Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: Kahwash
authors.affiliation: University of Arizona, Tucson, AZ (previous), USA.|Mayo Clinic, Scottsdale, AZ (current), USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.affiliation: Department of Hematology and HCT, City of Hope, Duarte, CA, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.affiliation: University of Rochester, James P. Wilmot Cancer Center, Rochester, NY, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Constine
authors.affiliation: Division of Hematology/Oncology, UNC School of Medicine, Chapel Hill, NC, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Shea
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Cashen
authors.affiliation: Division of Hematology, Ohio State University, Columbus, OH, USA.
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Blum
authors.affiliation: Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Fenske
authors.affiliation: Wilmot Cancer Institute, University of Rochester, Rochester, NY, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Barr
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: Tycel
authors.initials: T
authors.lastname: Phillips
authors.affiliation: SWOG Statistical Center, Seattle, WA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Leblanc
authors.affiliation: Fox Chase Cancer Center/Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
authors.affiliation: University of Chicago, Chicago, IL, USA.
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: Adaptive Biotechnologies Corp, South San Francisco, CA, USA.
authors.forename: Malek
authors.initials: M
authors.lastname: Faham
authors.affiliation: Adaptive Biotechnologies Corp, South San Francisco, CA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wilkins
authors.affiliation: Department of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.affiliation: University of Wisconsin, Madison (previous), WI, USA.|Washington University School of Medicine in St. Louis, St. Louis, MO (current), USA.
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.affiliation: University of Rochester, Rochester, NY, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage*; D003131:Combined Modality Therapy / Q000379:methods / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000401:mortality / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis; D012074:Remission Induction / Q000379:methods*; D000069283:Rituximab / Q000008:administration & dosage*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D000069461:Bendamustine Hydrochloride; D008727:Methotrexate
keywords: 
  MRD
  ; Auto-HCT; bendamustine; hyperCVAD; mantle cell