Premium
A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B‐cell non‐Hodgkin lymphoma: A Wisconsin Oncology Network study
Author(s) -
Fenske Timothy S.,
Shah Namrata M.,
Kim Kyung Mann,
Saha Sandeep,
Zhang Chong,
Baim Arielle E.,
Farnen John P.,
Onitilo Adedayo A.,
Blank Jules H.,
Ahuja Harish,
Wassenaar Tim,
Qamar Rubina,
Mansky Patrick,
Traynor Anne M.,
Mattison Ryan J.,
Kahl Brad S.
Publication year - 2015
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.29502
Subject(s) - medicine , temsirolimus , bortezomib , refractory (planetary science) , oncology , hodgkin lymphoma , lymphoma , discovery and development of mtor inhibitors , multiple myeloma , apoptosis , biochemistry , chemistry , protein kinase b , physics , astrobiology
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. Cancer 2015;121:3435–43. © 2015 American Cancer Society .