title: Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma.
abstract: Standard treatment of transplant-eligible patients with relapsed diffuse large B-cell lymphoma (DLBCL) consists of rituximab and platinum-based chemotherapy, either ifosfamide, carboplatin, and etoposide (ICE) or dexamethasone, cytarabine, and cisplatin (DHAP), with autologous transplant consolidation for those with chemosensitive disease. Nonetheless, outcomes are suboptimal for patients failing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We performed a multi-center phase II trial investigating the safety and efficacy of ofatumumab, a monoclonal antibody against CD20, combined with ICE or DHAP second-line therapy in patients with relapsed or refractory DLBCL, grade 3b follicular lymphoma, or transformed follicular lymphoma. Sixty-one patients were treated with either ofatumumab-ICE (35) or ofatumumab-DHAP (26). The overall response rate (ORR) was 61%, and the complete response (CR) rate was 37%. In patients with 2 or 3 adverse risk factors according to the second-line, age-adjusted, international prognostic index, the ORR was 59% and CR 31%, and in patients with early-relapsing or primary refractory disease, the ORR was 55% and CR 30%. Toxicity was largely hematologic, and stem cell mobilization was successful in 43 of 45 patients. Substitution of ofatumumab for rituximab in standard second-line regimens following failure of R-CHOP is a promising approach. This trial was registered at www.clinicaltrials.gov as NCT00823719.
authors.affiliation: Lymphoma and Adult Bone Marrow Transplant Services, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. matasarm@mskcc.org
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Matasar
authors.forename: Myron S
authors.initials: MS
authors.lastname: Czuczman
authors.forename: Maria Alma
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: Michael
authors.initials: M
authors.lastname: Fennessy
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Shea
authors.forename: Gary
authors.initials: G
authors.lastname: Spitzer
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
authors.forename: Robin
authors.initials: R
authors.lastname: Joyce
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
authors.forename: Kristen
authors.initials: K
authors.lastname: Henkel
authors.forename: Qiming
authors.initials: Q
authors.lastname: Liao
authors.forename: Klaus
authors.initials: K
authors.lastname: Edvardsen
authors.forename: Roxanne C
authors.initials: RC
authors.lastname: Jewell
authors.forename: Doug
authors.initials: D
authors.lastname: Fecteau
authors.forename: Rajendra P
authors.initials: RP
authors.lastname: Singh
authors.forename: Steen
authors.initials: S
authors.lastname: Lisby
authors.forename: Craig H
authors.initials: CH
authors.lastname: Moskowitz
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007167:Immunotherapy / Q000379:methods; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D012008:Recurrence; D016019:Survival Analysis; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D005047:Etoposide; D003907:Dexamethasone; D016190:Carboplatin; C527517:ofatumumab; D002945:Cisplatin; D007069:Ifosfamide