The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas

Abstract

Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin's lymphomas that are incurable in the majority of patients with current therapies. Outcomes associated with anthracycline-based therapies are suboptimal, but remain the standard of care for most patients, even though the benefits of this approach remain uncertain. This study retrospectively examined outcomes in a cohort of North American PTCL patients treated with both anthracycline- and nonanthracycline-containing regimens. The incorporation of anthracycline-containing regimens was associated with improved progression-free survival (PFS) and overall survival (OS). Patients treated with nonanthracycline-containing regimens were more likely to have high-risk features and were less likely to undergo high-dose therapy and stem cell transplantation. However, anthracycline use remained an independent predictor of improved PFS and OS when adjusting for these confounding variables. Anthracycline-based regimens and consolidation with high-dose therapy and autologous stem cell transplantation in appropriately selected patients remains a viable option for patients unable to participate in a clinical trial. Long-term disease-free survival is not optimal, highlighting the need for an improved understanding of disease pathogenesis, and the development of novel therapeutic strategies.

Peripheral T-cell lymphoma, not otherwise specified

“…Moreover, anthracycline-treated patients were more prone to receive bone marrow transplantation, either in first or second remission. 39 More intensive chemotherapy regimens have not proven to be more effective than CHOP in historical controls 38 ; moreover, in a phase 3 randomized study by Simon et al, an alternative induction schedule including etoposide, ifosfamide, and cisplatin, alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine did not show any superiority in terms of event-free survival (EFS) over CHOP (given every 21 days), thus confirming CHOP as the reference regimen for PTCL patients. 40 The role of adding etoposide to CHOP (CHOEP) during induction was investigated in depth by the German High-Grade Non-Hodgkin Lymphoma Study Group 41 : CHOEP, given either every 14 or 21 days, improved response and EFS rates in young patients with normal LDH levels (3-year EFS was 70.5% after CHOEP and 51.0% after CHOP, P 5 .004), although 3-year OS did not significantly differ between the 2 groups (81.3% for CHOEP vs 75.2% for CHOP, P 5 .285).…”

Comprehensive serum cytokine analysis identifies IL-1RA and soluble IL-2Rα as predictors of event-free survival in T-cell lymphoma

“…TCL are currently classified by WHO criteria [2,3], with the most common subtypes being peripheral TCL-not otherwise specified (PTCL-NOS), angioimmunoblastic TCL (AITL), anaplastic large cell (ALCL), and the predominant subsets of cutaneous TCL (CTCL), Sézary syndrome (SS) and mycosis fungoides (MF). The long-term outcome of the non-CTCL groups remains poor with ∼30% of patients being cured [4]. Induction therapy is typically with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus etoposide (CHOPE), and eligible patients typically receive autologous stem cell transplant in the first remission [5].…”

The mTORC1 inhibitor everolimus has antitumor activity in vitro and produces tumor responses in patients with relapsed T-cell lymphoma

“…9,30 Despite the recent approval of the histone deacetylase inhibitors romidepsin and belinostat and the antifolate pralatrexate, additional new agents are needed to improve outcome for these patients. In this report, we present promising results with the single-agent mTORC1 inhibitor everolimus for relapsed TCL.…”

“…Despite these advances, the overall prognosis of TCL remains inferior to B-cell NHL with only 30% of patients cured with frontline therapy. 9 The PI3K/Akt/mammalian target of rapamycin (mTOR) pathway has become an important focus for cancer therapeutic interventions with the approval of the PI3Kd inhibitor idelalisib for chronic lymphocytic leukemia and indolent B-cell NHL, 10,11 and the mTORC1 inhibitors temsirolimus and everolimus for solid tumors. We have reported that the PI3K/mTOR pathway is activated in NHL cells 12 and that mTORC1 inhibitors have activity in relapsed B-cell NHL.…”