Population-Based Analysis of Elderly Patients (>70 YEARS) with Peripheral T-CELL Lymphoma: A Results from Czech Lymphoma Study Group (CLSG) Registry
Authors: Janikova Andrea , Pytlik Robert , Klener Pavel , Bortlicek Zbynek , Campr Vit , Kopalova Natasa , Benesova Katerina , Hamouzova Michaela , Belada David , Prochazka Vit , Pirnos Jan , Duras Juraj , Mocikova Heidi , Mayer Jiri , Trneny Marek 
Published: October 2019

Abstract
INTRODUCTION:
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with usually poor prognosis. Age was identified as the independent risk factors in many studies. Elderly patients suffer from comorbidities, impaired organ functions, and poor performance status resulting in worse tolerance of therapy and its efficacy. Data on outcome, prognosis and treatment efficacy for elderly patients with PTCLs are sparse.
METHODS:
We used data of 941 newly diagnosed PTCLs registered into CLSG database between January 1999 and March 2015 with last follow-up in February 2016. CLSG database covers approximately 85% of all newly diagnosed NonHodgkin´s lymphomas (NHLs) in Czech Republic. For the analysis, 208 patients with age >70 years at diagnosis were selected.
RESULTS:
Totally, PTCLs accounted for about 8.7% (454/5210) patients of all NHLs in population younger 60 years, but only about 5.8% (208/3561) NHL patients older 70 years. Median age was 76ys (71-91ys), 94 (45%) were women, lactate dehydrogenase (LDH) was elevated in 130/208 (62.5%) pts., ECOG ≥2 had 80 (38%) pts., and advanced clinical stage III-IV presented 132/208 (63.5%) pts. We identified following PTCL subtypes: PTCL-NOS (Peripheral T-cell lymphoma not otherwise specified) 89/208 (43%), Anaplastic large cell lymphoma (ALCL) 34/208 (16.3%), Cutaneous Anaplastic large cell lymphoma (C-ALCL) 10/208 (4.8%), Mycosis fungoides/ Sézary syndrome (MF/SS) together 29/208 (14%), NK/T nasal lymphoma (NK/T) 2/208 (1%), Angioimmunoblastic lymphoma (AITL) 17/208 (8.1%), Cutaneous CD30+ T lymphoproliferative disease 1/208 (0.5%), T-lymphoblastic lymphoma/leukemia (T-LBL) 3/208 (1.4%), T-cell lymphoma without specification (T-NHL) 17/208 (8.1%). Distribution of PTCL subtypes changed significantly with age. There was higher proportion of PTCL-NOS (43% vs. 34%; p.001) and MF/SS (14% vs. 4.8%; p<.001) in elderly patients (>70ys) compared to younger cohort (≤70ys; n=725). Contrary, percentage of ALCL (16.3% vs. 27%; p<.001) with main difference in ALK+ cases (2% vs. 11%; p<.001), and NK/T (1% vs. 5%; p.003) was lower in elderly PTCLs, whereas the incidence of AITL (8.1% vs. 6.6%) or EATL (3.4% vs. 3%) was similar in both age subgroups.
For the whole cohort of PTCLs (>70ys), the 5-year overall survival (OS) was 30% and 5-year progression free survival (PFS) was 21% regardless of subtype or stage. Progression is fatal event in elderly patients with median survival about 8 months only. There were significant survival differences between patients (>70ys vs. ≤70ys) according to PTCL subtype; PTCL-NOS 5 yr-OS 23% vs. 43% (p.00001), ALCL ALK+ 5-yr OS not reached vs. 79% (p.01), ALCL ALK- 5 yr-OS 24% vs. 50% (p.001). Patients with AITL or EATL showed no age-related survival differences.
First-line chemotherapy was administered in majority of cases (67%); CHOP-like regimen was given in 78 (37%) pts., COP-like in 44 (21%) pts., and other chemotherapy in 18 (9%) cases. Local therapy (surgery, radiotherapy) was administered in first line in 17 (8%) pts., no or palliative therapy (corticoids) was given in 34 (17%) pts., initial therapy was unknown in 17 (8%) cases.
We compared two subgroups of patients according to first line chemotherapy CHOP (n=75) vs. COP (n=41). Median age was 74ys (71-84) vs. 79ys (71-89), high IPI was presented in 29% vs. 50% of patients (p.001). Complete response (CR) was achieved in 35/75 (47%) CHOP treated patients, and in 7/41 (17%) patients managed with COP (p.001). Contrary, there were 12/75 (16%) progression in CHOP arm compared to 10/41 (24%) COP treated pts. Five-year OS was 28% vs. 15% better in CHOP group (p.029) and 5-yr PFS 25% vs. 10%, respectively.
CONCLUSIONS: In population-based analysis of adult Caucasian PTCL patients, we identified mild decreasing incidence with age. There were significant age-related distribution differences of PTCL subtypes with shift to preponderance of PTCL-NOS, Mycosis fungoides, and NK/T nasal lymphoma in elderly. Worse survival in elderly PTCLs in comparison to younger patients was evident especially for PTCL-NOS and ALCL subtypes. Despite the baseline differences (COP managed pts. had higher IPI), there is tendency that anthracycline-based chemotherapy (CHOP) brings better results with higher proportion of CR and lower progression/relapse rate projected in longer survival.

Disclosures
Belada: Seattle Genetics: Research Funding. Mayer:AOP Orphan Pharmaceuticals: Research Funding; Novartis: Research Funding.