Autologous Stem Cell Transplantation in First Complete Remission May Not Extend Progression Free Survival in Patients with ALK-Negative Peripheral T Cell Lymphoma
Authors: Yam Clinton , Landsburg Daniel J. , Lin Xinyi , Mato Anthony , Svoboda Jakub , Loren Alison , Frey Noelle , Stadtmauer Edward A. , Porter David , Schuster Stephen J. , Dwivedy Nasta Sunita 
Published: October 2019

Abstract
Background: Peripheral T cell lymphoma (PTCL) is associated with a poor prognosis when treated with conventional front-line chemotherapy. Although consolidative autologous stem cell transplantation (ASCT) has been reported to improve progression free survival (PFS) when compared to historical controls, there is limited data comparing outcomes in PTCL patients undergoing ASCT versus active observation (AO) in first complete remission (CR1) following CHOP-based induction chemotherapy. Here we compare outcomes in this population at a single institution.
Methods: We conducted a retrospective cohort study of PTCL patients treated from 1/1/2007-12/31/2014 and collected data through 7/1/2015. Patients with ALK+ anaplastic large cell lymphoma and cutaneous T cell lymphoma were censored from this analysis. Response to induction chemotherapy was verified through a review of clinical notes and, where available, relevant imaging studies. Therapy was given at the discretion of the treating physician. Our primary outcome measure was PFS, defined as the time from diagnosis to relapse or most recent follow up. Kaplan Meier survival analysis and the log rank test were used to compare outcomes between patients who underwent consolidative ASCT versus those who initiated AO.
Results: We identified 105 PTCL patients who received a CHOP-based regimen as first line therapy. 52.4% (55/105) achieved CR1. Of these, 28 initiated AO, 20 underwent consolidative ASCT, 3 underwent consolidative radiation, 1 initiated weekly methotrexate and 3 were lost to follow up. There were no statistically significant differences in age, distribution of PTCL subtypes, IPI scores, stage, B symptoms, LDH, ECOG performance status and choice of primary therapy between the AO group and the ASCT group (Table 1). 28.6% (8/28) and 30.0% (6/20) of patients received etoposide as part of primary therapy in the AO and ASCT group respectively. After a median follow up duration of 22 months, median PFS for the AO and ASCT groups were 15.8 months (95% CI 7.8-23.7) and 12.8 months (95% CI 0-34.0) respectively (Figure 1, p=0.72).
Conclusion: In this study, consolidative ASCT was not associated with significantly improved PFS as compared to observation alone for PTCL patients achieving CR1 following CHOP-based induction chemotherapy. Our institutional experience highlights the poor prognosis of patients with PTCL despite an excellent initial response to cytotoxic chemotherapy. With that in mind, novel approaches, including the use of non-cytotoxic agents as part of first-line or consolidative therapy, should be considered in the context of a clinical trial.
Table 1. Baseline characteristics and choice of primary therapy AO (n=28) ASCT (n=20) P value Median age - years (range) 61.9 (32.8-78.3) 56.9 (21.4-71.9) 0.07 PTCL subtype PTCL NOS1 - no. (%) 16 (57.1) 6 (30.0) 0.41 AITL2 - no. (%) 5 (17.9) 6 (30.0) ALK- ALCL3 - no. (%) 5 (17.9) 3 (15.0) EATL4 - no. (%) 0 1 (5.0) ATLL5 - no. (%) 1 (3.6) 0 HSTCL6 - no. (%) 1 (3.6) 1 (5.0) Unknown - no. (%) 0 3 (15.0) IPI score at diagnosis 0-1 - no. (%) 5 (17.9) 3 (15.0) 1.00 2-3 - no.(%) 13 (46.4) 10 (50.0) 4-5 - no. (%) 3 (10.7) 2 (10.0) Unknown - no. (%) 7 (25.0) 5 (25.0) Stage at diagnosis I/II - no. (%) 7 (25.0) 4 (20.0) 0.73 III/IV - no. (%) 19 (67.9) 16 (80.0) Unknown - no. (%) 2 (7.1) 0 B symptoms at diagnosis Yes - no. (%) 17 (60.7) 13 (65.0) 1.00 No - no. (%) 9 (32.1) 7 (35.0) Unknown - no. (%) 2 (7.1) 0 LDH at diagnosis Elevated - no. (%) 12 (42.9) 11 (55.0) 0.46 Not elevated - no. (%) 7 (25.0) 3 (15.0) Unknown - no. (%) 9 (32.1) 6 (30.0) ECOG PS at diagnosis 0-1 - no. (%) 17 (60.7) 17 (85.0) 0.26 ≥2 - no. (%) 7 (25.0) 2 (10.0) Unknown - no. (%) 4 (14.3) 1 (5.0) Primary therapy CHOP - no. (%) 18 (64.3) 13 (65.0) 0.82 CHOP/Etoposide - no. (%) 7 (25.0) 6 (30.0) Other - no. (%) 3 (10.7)7 1 (5.0)8 1Peripheral T Cell Lymphoma, Not Otherwise Specified; 2Angioimmunoblastic T Cell Lymphoma; 3ALK negative Anaplastic Large Cell Lymphoma; 4Enteropathy Associated T Cell Lymphoma; 5Adult T Cell Leukemia/Lymphoma; 6Hepatosplenic T Cell Lymphoma; 72 patients received HyperCVAD and 1 patient received HyperCVED; 81 patient received CHOP alternating with DHAP

Disclosures
Mato: AbbVie: Consultancy, Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; Pronai Pharmaceuticals: Research Funding; Genentech: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding. Svoboda:Celgene: Research Funding; Immunomedics: Research Funding; Celldex: Research Funding; Seattle Genetics: Research Funding. Loren:Merck: Research Funding. Frey:Novartis: Research Funding. Porter:Novartis: Other: IP interest, Research Funding; Genentech: Other: Spouse employment. Schuster:Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Hoffman-LaRoche: Research Funding; Janssen: Research Funding; Gilead: Research Funding; Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding.