title: Safety and efficacy of Temsirolimus in combination with Bendamustine and Rituximab in relapsed mantle cell and follicular lymphoma.
abstract: In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with r/r follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1-3 prior therapies received Bendamustine (90 mg/m(2), day 1+2) and Rituximab (375 mg/m(2), day 1) with Temsirolimus in doses from 25 to 75 mg added on day 1, 8, 15 of a 28-day cycle. Fifteen (11 MCL, 4 FL) patients were included in the phase I. Median age was 73 years and median pretreatment number was 2. No formal dose-limiting toxicity was observed. Dominant non-hematological side effects were fatigue in 11 (73%), nausea in 9 (60%), mucositis in 7 (47%) and vomiting in 6 patients (40%). Cough, diarrhea, pyrexia and rash were observed in five patients (33%) each. Grade 3/4 events included leukopenia in 6 (40%), neutropenia in 4 (27%) and thrombocytopenia in 2 patients (13%). An objective response was observed in 14/15 patients (93%), including 5 complete response (33%; all MCL). After a median follow-up of 19 months, 67% of patients are without signs of progression. Temsirolimus can be safely added to BR with promising preliminary activity. Recruitment in phase II is ongoing.
authors.affiliation: Department of Internal Medicine III (Hematology, Oncology, Pneumology), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: G
authors.identifier: 0000000292825688
authors.initials: G
authors.lastname: Hess
authors.affiliation: III. Medical Department, Technical University Munich, Munich, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Keller
authors.affiliation: Department of Hematology, Oncology, Charité - University Medical School Berlin, Berlin, Germany.
authors.forename: C W
authors.initials: CW
authors.lastname: Scholz
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Witzens-Harig
authors.affiliation: Department of Internal Medicine II, Center of Internal Medicine, Johann Wolfgang Goethe-University, Frankfurt, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Atta
authors.affiliation: Institute of Experimental Cancer Research and Department of Internal Medicine III, University Hospital, Ulm, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Buske
authors.affiliation: Department of Internal Medicine III (Hematology, Oncology, Pneumology), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kirschey
authors.affiliation: Interdisciplinary Centre for Clinical Trials (IZKS), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Ruckes
authors.affiliation: Interdisciplinary Centre for Clinical Trials (IZKS), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Medler
authors.affiliation: Department of Internal Medicine III (Hematology, Oncology, Pneumology), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: C
authors.initials: C
authors.lastname: van Oordt
authors.affiliation: Division of Hematophathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Klapper
authors.affiliation: Department of Internal Medicine III (Hematology, Oncology, Pneumology), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Theobald
authors.affiliation: Department of Internal Medicine III, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Dreyling
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D000069283:Rituximab; D012449:Safety; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D015996:Survival Rate
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D009588:Nitrogen Mustard Compounds; D000069283:Rituximab; C401859:temsirolimus; D000069461:Bendamustine Hydrochloride; D020123:Sirolimus