Treatment Options of Mature, Nodal T-Cell Lymphomas

Special Article - T-Cell Lymphoma

Austin J Cancer Clin Res. 2016; 3(1): 1068.

Treatment Options of Mature, Nodal T-Cell Lymphomas

Illés Á and Miltényi Z*

Department of Hematology, Faculty of Medicine, University of Debrecen, Hungary

*Corresponding author: Zsófia Miltényi, Department of Hematology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98 4032 Debrecen, Hungary

Received: July 06, 2016; Accepted: August 02, 2016; Published: August 04, 2016


T-cell lymphomas represent only 10-15% of non-Hodgkin lymphomas. T cell lymphomas are more agressive, heterogenous diseases and have worse prognosis than B cell lymphomas. A number of new drugs are tested and approved in the therapy of peripherial T cell lymphomas, which hopefully will increase survival. CHOP and CHOP-like protocol are recommended for the first-line treatment, but it is efficacy alone only in ALK+ anaplastic large cell lymphoma. Guidelines recommend front-line autologous hematopoetic stem cell transplantation in the other most frequent subtypes. A number of new drugs are tested and approved in the therapy of peripherial T cell lymphomas, eg. romidepsin, pralatrexate, belinostat, brentuximab vedotin etc., which hopefully will increase survival.

Keywords: T cell lymphoma; Treatment; New drugs


AE: Adverse Event; AHSCT: Autologous Hemopoetic Stem Cell Transplantation; AITL: Angioimmunoblastic T Cell Lymphoma; ALCL: Anaplastic Large Cell Lymphoma; ALK: Anaplastic Lymphoma Kinase; CHOP: Cyclophosphamide, Doxorubicin, Vincristine and Prednisone; CHOEP: CHOP+etoposide; CR: Complete Remission; EFS: Event-Free Survival; FDA: Food and Drug Administration; FFS: Failure-Free Survival; HDAC: Histone Deacetylase; NCCN: National Comprehensive Cancer Network; NHL: Non-Hodgkin Lymphoma; OS: Overall Survival; PFS: Progression-Free Survival; PTCL-NOS: Peripherial T-Cell Lymphoma Not Otherwise Specified; TCL: T Cell Lymphoma; WHO: World Health Organization


Non-Hodgkin lymphomas (NHLs) originate from T lymphocytes and NK cells in 10-15% of cases, while T-cell lymphomas (TCL) represent approximately 25% of NHLs in Asian countries [1]. There are four main groups of T cell lymphomas in the WHO classification: nodal, extranodal, cutan and leukemic group. New provosional entities of T cell lymphomas are introduced in the new WHO 2016 classification, these changes mostly based on the result of genomic studies [2]. Three subtypes are the most frequent in nodal T cell lymphoma group: peripherial T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and systemic anaplastic large cell lymphoma (ALCL), which may be positive or negative for anaplastic lymphoma kinase (ALK) [2]. T cell lymphomas are more agressive, heterogenous diseases and have worse prognosis than B cell lymphomas. Usually patients have advanced stage disease and extranodal involvement at the time of diagnosis. The minority of patients reach durable remissions or cure after first-line treatment. Treatment of TCLs is unmet medical need nowadays. A number of new drugs are tested and approved in the therapy of PTCLs, which hopefully will increase survival.

Current first-line treatment options

Majority of PTCLs, except for ALK+ ALCL, has bad prognosis. The 5-year overall survival (OS) for ALK+ ALCL, ALK-ALCL, PTCL-NOS and AITL was 70%, 49%, 32% and 32% and the 5-year failure-free survival (FFS) was 60%, 36%, 20% and 18% [3]. The frontline treatment in the most frequent PTCL types is combination chemotherapy, usually anthracycline-based regimens, such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), or CHOP+etoposide (CHOEP) with autologous hemopoetic stem cell transplantation (AHSCT) given as consolidation for high risk, selected patients (except ALK+ ALCL) [4,5].

CHOP is the generally recommended and used protocol, but it has moderate efficacy. A retrospective analysis showed 5-year OS was only 37% in 2912 patients, who received CHOP or CHOP-like chemotherapy [6]. The only exception was ALK+ and ALK - ALCL, which has better survival, overall response rate (ORR) >75% and 5-year OS >60% [7]. PTCL-NOS patients who received anthracycline in the initial treatment has no survival benefit than patients who didn’t receive it [3].

There were a lot of trials to improve efficacy of the therapy. Some studies used combination therapy eg. CHOP plus etopozid or alemtuzumab, or another chemotherapy eg. ACVBP, VIP-rABDV, alemtuzumab, denileukin diftitox [8]. VIP/ABVD (etoposide/ ifosfamide/ cisplatin–doxorubicin/ bleomycin/ vinblastine/ dacarbazine), CHOP/ESHAP did not improve the outcome [9- 11]. Hyper-CVAD/MA (hyper-fractionated cyclophosphamide/ doxorubicin/ vincristine/ dexamethasone alternating with methotrexate/ cytarabine) showed higher ORR and progression-free survival (PFS), but not higher OS, than CHOP [12] in a retrospective study, but this regimen associated with greater toxicity.

The German High-Grade Lymphoma Study Group added etoposide to CHOP (CHOEP) [13]. ORR was 82% and complete remission) CR was 63%. Schmitz, et al. reported that CHOEP treatment is more effective than CHOP in young patients’ group, but this treatment was no significantly better in >60 years old patients and it was too toxic in this group [13].

The difference in event-free survival (EFS) for younger patients and ALK+ ALCL treated with CHOP or CHOEP was significant (3- year EFS for CHOEP patients 91.2% vs. 57.1% for patients treated with CHOP, p = 0.012), a statistically not significant difference was seen in the remaining patients when ALK+ ALCL was excluded (3- year EFS for CHOEP patients 60.7% vs. 48.3% for patients treated with CHOP, p = 0.057) [13].

CHOEP was associated with improved PFS in patients younger than 60 years in a Swedish analyzis also [14].

Autologous transplantation is recommended ALK-ALCL patients in first-line treatment, but not in ALK+ALCL patients [5]. D’Amore, et al. showed 5-year OS 70% and PFS 61% in ALK-ALCL patients who were treated 6 cycles CHOEP followed by AHSCT, if they were in CR/ CRu or PR [15]. AHSCT produces better 5-year OS in ALK+ than ALK-patients (82% versus 54%) [16].

Based on these results National Comprehensive Cancer Network (NCCN) guidelines recommend CHOP-21 or CHOEP-21 regimens as the first-line therapy in ALK-positive ALCL and clinical trials and/ or frontline AHSCT for first-line therapy in all other subtypes [5].

New therapeutic options

Only half of the TCL patients reached complete remission (CR) after first line treatment and only half of these patients have durable remission [17]. Majority of T-cell lymphoma patients (about 70%) have refractory disease or relapse after the first line treatment [4]. Relapsed/refractory (R/R) PTCL patients’ overall survival (OS), who did not undergo AHSCT, 5.5 months only [18].

There is no uniform recommendation to the optimal treatment relapsed and refractory patients. A lot of clinical trials was conducted and these showed various efficacy (Table 1,2). Three new drugs was approved by the FDA in the therapy of R/R PTCL patients, pralatrexate, romidepsin and belinostat.