Faculty Collaboration Database

A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B-cell non-Hodgkin lymphoma: A Wisconsin Oncology Network study. Cancer 2015 Oct 01;121(19):3465-71

Date

06/17/2015

Pubmed ID

26079295

DOI

10.1002/cncr.29502

Scopus ID

2-s2.0-84941940489 (requires institutional sign-in at Scopus site)   37 Citations

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.

Author List

Fenske TS, Shah NM, Kim KM, Saha S, Zhang C, Baim AE, Farnen JP, Onitilo AA, Blank JH, Ahuja H, Wassenaar T, Qamar R, Mansky P, Traynor AM, Mattison RJ, Kahl BS

Author

Jules H. Blank MD Adjunct Assistant Professor in the Medical School Regional Campuses department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Antineoplastic Combined Chemotherapy Protocols
Bortezomib
Disease-Free Survival
Female
Humans
Incidence
Lymphoma, Non-Hodgkin
Male
Sirolimus
Wisconsin