title: Early treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14.
abstract: In the treatment of diffuse large B-cell lymphoma, a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan-BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17-20 of cycle 4 and assessed according to International Harmonisation Project criteria. Median age of the 151 evaluable patients was 57 years, with 79% stages 3-4, 54% bulk, and 54% International Prognostic Index 3-5. Among the 143 patients undergoing interim PET, 101 (71%) were PET-negative (96 of whom completed R-CHOP), 42 (29%) were PET-positive (32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM). At a median follow up of 35 months, the 2-year progression-free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression-free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001, respectively). Therefore, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and who switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieved favorable survival outcomes similar to those for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (Registered at: ACTRN12609001077257).
authors.affiliation: Department of Haematology, Prince of Wales Hospital and University of NSW, Randwick, NSW, Australia mhertzberg10@gmail.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Hertzberg
authors.affiliation: The University of Queensland Diamantina Institute Woolloongabba, Brisbane, QLD, Australia.|Department of Haematology, Princess Alexandra Hospital Brisbane, QLD, Australia.
authors.forename: Maher K
authors.initials: MK
authors.lastname: Gandhi
authors.affiliation: Department of Haematology, Repatriation General Hospital Concord and University of Sydney, NSW, Australia.
authors.forename: Judith
authors.initials: J
authors.lastname: Trotman
authors.affiliation: WriteSource Medical Pty Ltd., Lane Cove, NSW, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Butcher
authors.affiliation: Nepean Cancer Care Centre, Nepean Hospital Nepean, NSW, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Taper
authors.affiliation: Department of Haematology, Westmead Hospital, NSW, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Johnston
authors.affiliation: Department of Haematology, Princess Alexandra Hospital Brisbane, QLD, Australia.
authors.forename: Devinder
authors.initials: D
authors.lastname: Gill
authors.affiliation: Department of Haematology, St George Hospital Kogarah, NSW, Australia.
authors.forename: Shir-Jing
authors.initials: SJ
authors.lastname: Ho
authors.affiliation: Department of Haematology, Sir Charles Gairdner Hospital Perth, WA, Australia.
authors.forename: Gavin
authors.initials: G
authors.lastname: Cull
authors.affiliation: Department of Haematology, Royal North Shore Hospital, St Leonard's, NSW, Australia.
authors.forename: Keith
authors.initials: K
authors.lastname: Fay
authors.affiliation: Olivia Newton John Cancer & Wellness Centre, Austin Hospital, Heidelberg, VIC, Australia.
authors.forename: Geoff
authors.initials: G
authors.lastname: Chong
authors.affiliation: Department of Haematology, Austin Hospital, Heidelberg, VIC, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Grigg
authors.affiliation: Department of Haematology, Royal Adelaide Hospital Adelaide, SA, Australia.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Lewis
authors.affiliation: Department of Haematology, St Vincent's Hospital Darlinghurst, NSW, Australia.
authors.forename: Sam
authors.initials: S
authors.lastname: Milliken
authors.affiliation: Department of Haematology, Royal Melbourne Hospital Parkville, VIC, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Renwick
authors.affiliation: Department of Haematology, The Queen Elizabeth Hospital, SA, Australia.
authors.forename: Uwe
authors.initials: U
authors.lastname: Hahn
authors.affiliation: Department of Haematology, St Vincent's Hospital Melbourne, VIC, Australia.
authors.forename: Robin
authors.initials: R
authors.lastname: Filshie
authors.affiliation: Ballarat Oncology and Haematology Service and Fiona Elsey Cancer Research Institute, Ballarat, VIC, Australia.
authors.forename: George
authors.initials: G
authors.lastname: Kannourakis
authors.affiliation: Department of Haematology, Liverpool Hospital, Liverpool, NSW, Australia.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Watson
authors.affiliation: Department of Haematology, Wollongong Hospital, Wollongong, NSW, Australia.
authors.forename: Pauline
authors.initials: P
authors.lastname: Warburton
authors.affiliation: Department of Radiation Oncology, Peter MacCallum Cancer Centre East Melbourne, VIC, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wirth
authors.affiliation: Department of Haematology, Peter MacCallum Cancer Centre East Melbourne and University of Melbourne, Parkville, VIC, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.affiliation: Department of Cancer Imaging, Peter MacCallum Cancer Centre East Melbourne, VIC, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hofman
authors.affiliation: Department of Cancer Imaging, Peter MacCallum Cancer Centre East Melbourne, VIC, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002330:Carmustine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D016403:Lymphoma, Large B-Cell, Diffuse / Q000000981:diagnostic imaging* / Q000401:mortality / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D011034:Podophyllotoxin / Q000627:therapeutic use; D049268:Positron-Emission Tomography / Q000379:methods; D011241:Prednisone / Q000627:therapeutic use; D019233:Retreatment; D000069283:Rituximab / Q000008:administration & dosage; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D003561:Cytarabine; D019788:Fluorodeoxyglucose F18; D000069283:Rituximab; C422802:ibritumomab tiuxetan; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine; D007069:Ifosfamide; D011241:Prednisone