A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B-cell non-Hodgkin lymphoma: A Wisconsin Oncology Network study

Timothy S. Fenske, Namrata M. Shah, Kyung Mann Kim, Sandeep Saha, Chong Zhang, Arielle E. Baim, John P. Farnen, Adedayo A. Onitilo, Jules H. Blank, Harish Ahuja, Tim Wassenaar, Rubina Qamar, Patrick Mansky, Anne M. Traynor, Ryan J. Mattison, Brad S. Kahl

Research output: Contribution to journalArticlepeer-review

33 Scopus 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.

Original languageEnglish
Pages (from-to)3465-3471
Number of pages7
JournalCancer
Volume121
Issue number19
DOIs
StatePublished - Oct 1 2015

Keywords

  • bortezomib
  • clinical trial
  • non-Hodgkin lymphoma
  • phase 2
  • temsirolimus

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