Suboptimal/Reduced Therapy in Older Patients with T-Cell Lymphoma Resulted in Poorer Outcomes: Report from the International T-Cell Project 1.0

Background: Peripheral T-cell lymphomas (PTCLs), rare heterogeneous aggressive non-Hodgkin lymphoma (NHL) subtypes, generally have poor outcomes for all patient age groups. Few data are available on the clinical features and treatment outcomes for older adults with PTCLs. Given this gap in the literature, the purpose of this sub-analysis was to assess the clinical information, therapeutic approaches, and outcome of patients (>65 years old) included in the T-Cell Project 1.0 (clinicaltrials.gov: 01142674) and to investigate potential prognostic factors.

Methods: The TCP 1.0 is a prospective international registry that collected clinical data and biological information of 1553 cases with PTCL at 75 institutions worldwide between 2006-2018. We identified 566 patients aged 65+. Baseline patient characteristics have been summarized with descriptive statistics. Survival analyses were performed using Kaplan-Meier method.

Results: The median age of patients >65 years old was 72 years (range 65-90) with a slight male predominance (56.4%). The majority had ECOG 0-1 (65.8 %) and advanced stage III/IV (62%), and 44.5% of cases had extranodal involvement. The most frequent histological subtypes were PTCL NOS (236 cases, 41.7%), AITL (159, 28.1%), and ALCL ALK neg (69, 12.2%). The median follow-up for living patients was 36 months (2-139 months). Five year overall survival (OS) and progression-free survival (PFS) were 31% and 14%, respectively. B symptoms (p<0.001), weight loss (p<0.001), ECOG >1 (p<0.001), LDH>UNL (p<0.001), IPI 3-5 (p<0.001), beta2 microglobulin (p=0.002), suboptimal/reduced therapy (p<0.001), and age 75+ (p < 0.001) were correlated with lower OS in univariate analysis. Adverse prognostic features for PFS were B symptoms (p<0.001), weight loss >10% (p<0.001), ECOG >1 (p<0.001), advanced stage (p =0.04), LDH>UNL (p<0.001), IPI 3-5 (p=0.002), PIT 3-4 (p<0.001), suboptimal/reduced therapy (p<0.001), and age 75 + (p < 0.001). Interestingly, there were no differences in clinical characteristics between patients 65-74 years old and those 75+. However, optimal therapy was delivered to 89% of patients 65-74 and only to 67% in those aged 75 or more.

Conclusion: In this prospective cohort of patients, we found no differences in clinical presentation between 65-74 and 75+ age groups. It seems they may have biologically similar disease. Older patients with PTCL are frequently treated with suboptimal/reduced therapy and exhibit a poorer outcome compared to those treated with optimal therapy. Based on the obtained results, the inclusion of otherwise fit older patients in ongoing clinical trials of front-line therapies incorporating targeted agents with a better tolerance is warranted.

Vose:Abbvie: Honoraria, Research Funding; GenMab: Honoraria, Research Funding; Novartis: Honoraria; Pfizer: Research Funding. Hitz:Abbvie: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche Pharma: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Kim:Boryong: Research Funding; BeiGene: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Donga: Research Funding; Sanofi: Research Funding; Kyowa-Kirin: Research Funding. Advani:Merck: Other: Steering committee, DSMB/Advisory Boards, Research Funding; Gilead: Research Funding; Autolus: Honoraria, Other: DSMB/Advisory Boards; Regeneron: Research Funding; Cyteir: Research Funding; Seattle Genetics: Research Funding; ADCT: Honoraria, Other: DSMB/Advisory Boards; BeiGene: Honoraria, Other: DSMB/Advisory Boards, Research Funding; Roche/Genentech: Honoraria, Other: Steering committee, DSMB/Advisory Boards, Research Funding. Stelitano:Roche, Novartis, Sandoz,Morphosys, Takeda, Octapharma, Celgene: Other: Investigartor of clinical trials. Porcu:DAIICHI: Consultancy, Honoraria; Innate-Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kiowa Kirin: Honoraria, Research Funding; ONO: Consultancy, Research Funding; SOBI: Consultancy, Honoraria, Speakers Bureau; Teva: Consultancy, Research Funding; Viracta therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.