Early Complete Remission By Functional Imaging and Intensified Frontline Therapy Are Associated with an Improved Clinical Outcome in Patients with Newly Diagnosed T-Cell Lymphoma- a Single Center Experience
Authors: Sundaram Suchitra , Gravina Matthew , Torka Pallawi , Attwood Kristopher , Hernandez-Ilizaliturri Francisco J. 
Published: November 2019

Objectives: T-cell lymphomas (TCL) pose a significant therapeutic challenge due to their aggressive behavior and poor response to treatment. Significant controversy exists regarding the benefit of intensification of therapy in the frontline and relapse settings due the lack of randomized studies in this rare and heterogenous population. We performed a retrospective analysis of survival outcomes in our cohort of TCL patients (pts) to assess the impact of intensification of therapy and other baseline disease, treatment and response characteristics.
Methods: Adult pts with TCL diagnosed between January 2001 to December 2018 at Roswell Park Comprehensive Cancer Center were included in this single institution, retrospective chart review. Pts were classified according to the 2008 WHO classification of lymphomas. Demographics, pathology and treatment data were collected across all subtypes. Survival outcomes were summarized by treatment type using standard Kaplan-Meier methods. Comparisons were made using the log-rank test. All other statistics were descriptive.
Results:
Eighty-seven pts were included in our study. Histological subtypes of TCL included: 27 (31%) peripheral TCL-unspecified (PTCL-U), 15 (17%) Angioimmunoblastic TCL (AITL), 30 (34.5%) anaplastic large cell lymphoma (ALCL), out of which 10/30(33%) were ALK+ ALCL, 11(12.6%) NK TCL, 4(4.6%) enteropathy associated TCL (EATCL). Median age at diagnosis was 62 yrs (range, 20-92), 39 pts (68%) had stage IV disease, 11 pts (12.6%) had ECOG performance status >2, 21 (24%) with IPI risk of 3-4. Fourteen pts (18.6%) received Hyper-CVAD, 54 pts (72%) received CHOP and 7 pts (9.3%) received CHOEP. Others were treated with either less intensive chemotherapy (n=10), SMILE (n=1) or CMED (n=1). With a median follow up of 94 months (mo), the median OS for the entire cohort was 79 mo (95% CI 45.9-127.4). Complete remission (CR) on interim PET (after 2 cycles of therapy) was seen in 29 pts (53.7%) and this was associated with significantly higher CR rates at the end of treatment as well as improved PFS and OS (NR vs 6.7 mo; p=0.001; NR vs 48 mo; p=0.003) (Figure 1). Impact of frontline therapy was assessed in PTCL pts excluding NK TCL and EATCL (Total n=67). Pts treated with Hyper CVAD or those with CHOP/CHOEP followed by high dose chemotherapy and autologous stem cell transplant (HDC-ASCT) were grouped into the Intensive upfront therapy (IUT) group and compared with less intensive upfront therapy (LIUT) that included CHOP/CHOEP or other chemotherapy (Table 1). IUT (n=17; 25.4%) as compared to LIUT (n=50; 74.6%) had improved PFS (5yr PFS 64 mo vs 33 mo, p=0.037), although OS did not reach statistical significance (5yr OS 70 mo vs 48 mo, p=0.24). (Figure 2).
A total of 48 pts (55%) in the entire cohort had relapse/progression(R/P). Pts with early relapse (ER) <12 mo from diagnosis compared to late relapse (LR) > 12 mo were associated with a significantly lower 5 yr OS (18%; 95% CI 7-33; vs 53%; 95 % CI 29-72). For pts with ER, median OS after progression was only 2.4 mo, as compared to those with LR (14.2 mo). Notably, among pts who received IUT, 4 pts had ER (23.5%); whereas 23 pts (46%) with LIUT had ER. While, this did not meet statistical significance, our cohort may be underpowered to find a true effect. At R/P, 20 pts (41.7%) received multiagent salvage (mostly ICE/CHOP or cytarabine based), 18 pts (37.5%) received single agent therapy (mostly romidepsin), while 10 pts (20.8%) were placed on hospice. As compared to single agent therapy, multiagent salvage was associated with improved median PFS2 and OS2 (calculated from time of R/P to second progression or death) [mPFS 10.4 vs 3.4 mo; p= 0.01; mOS 14.2 vs 5.8 mo; p= 0.004] (Figure 3).
Conclusions:
While the ideal front-line therapy for TCL continues to be a subject of debate, the use of intensified front-line chemotherapy and/or early HDC-ASCT appears to be associated with better PFS in our cohort of TCL. Attaining an early CR by functional imaging was associated with improved survival. Pts with early relapse of disease or refractoriness to frontline therapy had a dismal overall survival. Use of multiagent intensive salvage therapy over single agent therapy at the time of relapse may improve outcomes. Further analysis on factors influencing choice of salvage treatment strategy at relapse would be important to study.

Disclosures
No relevant conflicts of interest to declare.