Survival of Newly Diagnosed T-Cell Lymphoma (TCL) in the Modern Era: Investigation of Prognostic Factors with Critical Examination of Therapy in a Multicenter US Cohort.
Authors: Evens Andrew M. , Feldman Tatyana , Kroll Aimee , Muffly Lori S. , Winer Eric , Flowers Christopher , Lansigan Frederick , Nabhan Chadi , Nastoupil Loretta , Kim Austin , Li Xiuning , Waksmundzki Kathryn , Lam David , Draper Jacqueline Tessa , Meilleur Ashley , Nath Rajneesh , Cygan Peter , Castillo Jorge J , Goy Andre , Woda Bruce , Smith Sonali M. , Rosen Steven T. , Abramson Jeremy S. 
Published: October 2019

Abstract
Abstract 2728

Background:
TCLs are uncommon malignancies consisting of heterogeneous pathologic subtypes and outcomes. Despite development of prognostic models, there is little data of outcomes in large cohorts examining the impact of frontline therapy and the role of consolidative stem cell transplantation (SCT).

Methods:
We performed a multi-center retrospective analysis of a large cohort of newly diagnosed mature TCLs (non-cutaneous) from 2000–2010 across 9 U.S. academic centers. We examined detailed information regarding patient characteristics and treatment(s) received. Further, we determined prognostic factors for associations with survival in univariate analysis and multivariate Cox regression proportional models.

Results:
Among 402 cases of mature TCL, 341 had complete treatment and follow-up data. This included 107 cases of peripheral TCL (PTCL NOS), 89 anaplastic large cell lymphoma (ALCL), 77 angioimmunoblastic TCL (AITL), 23 NK/TCL, 20 acute t-cell leukemia/lymphoma (ATLL), 10 enteropathy-associated TCL (EATCL), 7 subcutaneous panniculitis-like TCL (SCPTCL), 5 hepatosplenic TCL (HSL), and 4 transformed CTCL (t-CTCL) cases. 60% of pts were men and the median age was 62 years (range 18–95). At initial diagnosis, performance status was 2–4 in 36%, B symptoms in 47%, elevated LDH in 55%, anemia in 64%, and hypoalbuminemia in 46% at baseline. 74% of pts had advanced-stage disease, 29% had bone marrow involvement, 52% had other (non-marrow) extranodal sites, and only 9% had bulky disease >7cm. Twenty-three pts received only palliative therapy all of whom survived <3.5 months. Among the remaining 318 pts, CHOP-like therapy was the most common initial regimen (74%; 5% of which included etoposide), 7% hyperCVAD/MA, 3% EPOCH, 2% CMED, 2% gemcitabine-based, 2% ifosfamide-based, and 10% other. 21% received radiation therapy (RT) as part of initial treatment, while 34 pts (11%) received a SCT in 1st remission (85% autologous). Overall response to therapy was 73% (61% complete), while 24% had primary refractory disease. With a median follow-up of 38 months (6–109), 3-year progression-free survival (PFS) and overall survival (OS) for all pts were 32% and 52%, respectively (Figure). Factors predictive of outcome by univariate analysis are detailed in the Table (includes differential survival by WHO subtype and PIT and IPI). On multivariable regression analysis of pre-treatment factors, only Ann Arbor stage I/II remained significant (PFS: HR 0.59 [95%CI 0.38–0.93], p=0.023); and OS: HR 0.46 [95%CI 0.25–0.85], p=0.013). Regarding induction treatment, the only impact based on regimens received were inferior outcomes with CMED or EPOCH therapy; these findings persisted on multivariate analysis. The addition of etoposide to CHOP did not appear to impact outcome, although those numbers were small. Notably, consolidative SCT portended significantly improved survival on multivariate analysis when controlling for gender, LDH, albumin, and stage (PFS: HR 0.46 [95%CI 0.24–0.89], p=0.02; and OS: 0.43 [95%CI 0.19–0.99], p=0.04), but this did not reach significance when adjusting for response to 1st therapy (PFS: HR 0.55 [95%CI 0.28–1.08], p=0.08; OS: HR 0.47 [95%CI 0.17–1.29], p=0.14).

Conclusions:
In this large US cohort of TCL, response, PFS, and OS compared favorably with historical controls. Further, we documented that NK/TCL, AITL, and ALCL (ALK+ and negative) were all associated with improved OS vs PTCL NOS. On multivariable analysis, limited-stage disease was the predominant predictive factor for survival. Additionally, consolidative SCT was associated with improved PFS and OS, however this benefit appeared to be nullified after controlling for initial response.

Disclosures:
No relevant conflicts of interest to declare.