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

• Published in: Cancer 2015-10, Vol.121 (19), p.3465-3471
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; bortezomib; Bortezomib - administration & dosage; Bortezomib - therapeutic use; clinical trial; Disease-Free Survival; Female; Humans; Incidence; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - mortality; Male; non‐Hodgkin lymphoma; phase 2; Sirolimus - administration & dosage; Sirolimus - analogs & derivatives; Sirolimus - therapeutic use; temsirolimus; Wisconsin
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.29502

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. The combination of bortezomib and temsirolimus demonstrates activity in patients with previously treated relapsed/ refractory B‐cell non‐Hodgkin lymphoma. An overall response rate of 31% was seen, including complete remissions in two heavily pre‐treated patients with diffuse large B‐cell lymphoma.