title: Early failure of frontline rituximab-containing chemo-immunotherapy in diffuse large B cell lymphoma does not predict futility of autologous hematopoietic cell transplantation.
abstract: The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P <.001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: mhamadani@mcw.edu.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Parameswaran N
authors.initials: PN
authors.lastname: Hari
authors.affiliation: Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Carreras
authors.affiliation: Section of Hematology Oncology at Banner MD Anderson Cancer Center, Gilbert, Arizona.
authors.forename: Görgün
authors.initials: G
authors.lastname: Akpek
authors.affiliation: Department of Oncology, King Faisal Specialist Hospital Center and Research, Riyadh, Saudi Arabia.
authors.forename: Mahmoud D
authors.initials: MD
authors.lastname: Aljurf
authors.affiliation: Blood and Marrow Transplantation Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Ayala
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, Minnesota.
authors.forename: Veronika
authors.initials: V
authors.lastname: Bachanova
authors.affiliation: Blood and Marrow Transplant Program, Oregon Health and Science University, Portland, Oregon.
authors.forename: Andy I
authors.initials: AI
authors.lastname: Chen
authors.affiliation: Department of BMT, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
authors.affiliation: Blood and Marrow Transplant Program, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Luciano J
authors.initials: LJ
authors.lastname: Costa
authors.affiliation: Division of Hematology and Oncology, Froedtert & Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Fenske
authors.affiliation: Blood and Marrow Transplant Program, South Texas Veterans Health Care System and University of Texas Health Science Center San Antonio, San Antonio, Texas.
authors.forename: César O
authors.initials: CO
authors.lastname: Freytes
authors.affiliation: BMT Program, Saint Luke's Blood & Marrow Transplant Program, Westwood, Kansas.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Ganguly
authors.affiliation: Department of Haematology, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Hertzberg
authors.affiliation: Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Leona A
authors.initials: LA
authors.lastname: Holmberg
authors.affiliation: Department of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: David J
authors.initials: DJ
authors.lastname: Inwards
authors.affiliation: Department of Hematology/Oncology, Baylor College of Medicine and the Center for Cell and Gene Therapy, Houston, Texas.
authors.forename: Rammurti T
authors.initials: RT
authors.lastname: Kamble
authors.affiliation: Department of Hematology, Imperial College NHS Trust, Hammersmith Hospital, London, United Kingdom.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Kanfer
authors.affiliation: Blood and Marrow Transplant Program, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Adult BMT Unit, University Hospitals Britol NHS Trust, Bristol, United Kingdom.
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.affiliation: Blood and Marrow Transplantation Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.affiliation: Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.
authors.forename: Richard
authors.initials: R
authors.lastname: Olsson
authors.affiliation: Blood and Marrow Transplant Program, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Nishitha M
authors.initials: NM
authors.lastname: Reddy
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
authors.affiliation: Blood and Marrow Transplant Program, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, Minnesota.
authors.forename: Melhem
authors.initials: M
authors.lastname: Solh
authors.affiliation: Department of Internal Medicine, The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.affiliation: BMT Program, Stony Brook University Medical Center, Stony Brook, New York.
authors.forename: Baldeep
authors.initials: B
authors.lastname: Wirk
authors.affiliation: Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.affiliation: Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois.
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: Department of Haemato-oncology, St. Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom.
authors.forename: Silvia
authors.initials: S
authors.lastname: Montoto
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Wael
authors.initials: W
authors.lastname: Saber
authors.forename: Onder
authors.initials: O
authors.lastname: Alpdogan
authors.forename: Amanda
authors.initials: A
authors.lastname: Cashen
authors.forename: Christopher
authors.initials: C
authors.lastname: Dandoy
authors.forename: Robert
authors.initials: R
authors.lastname: Finke
authors.forename: Robert
authors.initials: R
authors.lastname: Gale
authors.forename: John
authors.initials: J
authors.lastname: Gibson
authors.forename: Jack W
authors.initials: JW
authors.lastname: Hsu
authors.forename: Nalini
authors.initials: N
authors.lastname: Janakiraman
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Laughlin
authors.forename: Michael
authors.initials: M
authors.lastname: Lill
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
authors.forename: Reinhold
authors.initials: R
authors.lastname: Munker
authors.forename: Phil A
authors.initials: PA
authors.lastname: Rowlings
authors.forename: Harry C
authors.initials: HC
authors.lastname: Schouten
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Shea
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Stiff
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000069283:Rituximab; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014182:Transplantation, Autologous; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab
keywords: Aggressive lymphoma; Autologous transplantation; Diffuse large B cell lymphoma; Early failure; High-dose therapy; Non-Hodgkin lymphoma; Rituximab