title: A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B-cell non-Hodgkin lymphoma: A Wisconsin Oncology Network study.
abstract: BACKGROUND
  Proteasome inhibitors and mammalian target of rapamycin inhibitors each have activity in various B-cell malignancies and affect distinct cellular pathways. Their combination has demonstrated synergy in vitro and in mouse models.
  
  
  METHODS
  The authors conducted a single-arm, phase 2 trial of combined temsirolimus and bortezomib in patients with relapsed and refractory B-cell non-Hodgkin lymphoma (NHL) using a dosing scheme that was previously tested in multiple myeloma. The patients received bortezomib and temsirolimus weekly on days 1, 8, 15, and 22 of a 35-day cycle.
  
  
  RESULTS
  Of 39 patients who received treatment, 3 achieved a complete response (7.7%; 95% confidence interval [CI], 1.6%-21%), and 9 had a partial response (PR) (23%; 95% CI, 11%-39%). Thus, the overall response rate (12 of 39 patients) was 31% (95% CI, 17%-48%), and the median progression-free survival was 4.7 months (95% CI, 2.1-7.8 months; 2 months for patients with diffuse large B-cell lymphoma [n = 18], 7.5 months for those with mantle cell lymphoma [n = 7], and 16.5 months for those with follicular lymphoma [n = 9]). Two extensively treated patients with diffuse large B-cell lymphoma achieved a complete response. There were no unexpected toxicities from the combination.
  
  
  CONCLUSIONS
  The current results demonstrate that the combination of a mammalian target of rapamycin inhibitor and a proteasome inhibitor is safe and has activity in patients with heavily pretreated B-cell NHL. Further studies with this combination are warranted in specific subtypes of NHL.
authors.affiliation: Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Fenske
authors.affiliation: Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Namrata M
authors.initials: NM
authors.lastname: Shah
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
authors.forename: Kyung Mann
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Saha
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Arielle E
authors.initials: AE
authors.lastname: Baim
authors.affiliation: Gundersen Lutheran Health System, La Crosse, Wisconsin.
authors.forename: John P
authors.initials: JP
authors.lastname: Farnen
authors.affiliation: Marshfield Clinic, Weston, Wisconsin.
authors.forename: Adedayo A
authors.initials: AA
authors.lastname: Onitilo
authors.affiliation: St. Vincent Regional Cancer Center, Green Bay, Wisconsin.
authors.forename: Jules H
authors.initials: JH
authors.lastname: Blank
authors.affiliation: Aspirus Regional Cancer Center, Wausau, Wisconsin.
authors.forename: Harish
authors.initials: H
authors.lastname: Ahuja
authors.affiliation: ProHealth Care Cancer Center, Waukesha, Wisconsin.
authors.forename: Tim
authors.initials: T
authors.lastname: Wassenaar
authors.affiliation: Aurora Cancer Care, Wauwatosa, Wisconsin.
authors.forename: Rubina
authors.initials: R
authors.lastname: Qamar
authors.affiliation: Bellin Health, Green Bay, Wisconsin.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mansky
authors.affiliation: Department of Medicine, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traynor
authors.affiliation: Department of Medicine, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Mattison
authors.affiliation: Department of Medicine, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069286:Bortezomib / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015994:Incidence; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014922:Wisconsin
chemical_list: C401859:temsirolimus; D000069286:Bortezomib; D020123:Sirolimus
keywords: bortezomib; clinical trial; non-Hodgkin lymphoma; phase 2; temsirolimus