Journal
ANNALS OF ONCOLOGY
Volume 27, Issue 4, Pages 712-718Publisher
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdv624
Keywords
everolimus; CHOP; T-cell lymphoma
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Funding
- Novartis
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI)
- Ministry of Health & Welfare, Republic of Korea [HI14C2223]
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Everolimus plus CHOP is effective for newly diagnosed, chemotherapy-naive peripheral T-cell lymphoma patients with acceptable toxicity.Everolimus, an oral mTOR inhibitor, has single-agent activity against relapsed lymphomas. Thus, we carried out a phase II study of everolimus in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) as a first-line treatment for patients with peripheral T-cell lymphoma (PTCL) based on our phase I study results. Participants (n = 30) received CHOP with 5 mg everolimus per day from day 1 to 14 every 21 days for a total of six cycles. The primary end point was the overall response rate (ORR), which included complete response (CR) and partial response (PR) to this regimen. Immunohistochemistry was used to evaluate the expression of phosphatase and tensin homology (PTEN) and phosphorylated S6 kinase (pS6K) as a response. The objective response rate was 90% with CR (n = 17) and PR (n = 10). The CR rate was different among subtypes; angioimmunoblastic T-cell lymphoma (AITL, n = 3) had a CR whereas PTCL-not-otherwise specified and ALK-negative anaplastic large-cell lymphoma (ALCL) patients showed 63% (12/19) and 29% (2/7) of CR rate, respectively. This difference in CR rate among subtypes was associated with PTEN loss because PTEN loss was not seen in AITL but 33% of ALCL patients. The most common toxicity was hematological, with 80% of patients experiencing at least one event of grade 3/4 neutropenia, and 60% of patients had grade 3/4 thrombocytopenia. The everolimus plus CHOP was effective for PTCL patients, and its efficacy might be related with the preservation of PTEN.
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