Background: Compared to other peripheral T cell lymphomas (PTCLs), patients with AITL have an aggressive clinical course and poor outcomes with conventional chemotherapies. Previous studies reported overall survival (OS) of <40% at 5 years. Furthermore, the prognostic factors of AITL are not well established, particularly because they are derived from the composite of all types of PTCL. In order to elucidate clinical characteristics and biomarkers with prognostic significance in patients with AITL, we conducted a single institution, retrospective study.
Methods: We performed a retrospective chart review for newly diagnosed AITL at our institution between February 1998 to August 2019. Patients with available clinical data were included in the analysis. Endpoints were progression-free survival (PFS) and OS. Other endpoints were to identify prognostic factors associated with survival. Univariate (UVA) and multivariate (MVA) Cox proportional hazards models were fitted to the data to assess the significance of variables at diagnosis on OS. A landmark analysis was conducted using only patients who achieved a complete remission (CR).
Results: A total of 109 patients with a median age of 66 (range, 28-83) years and female predominance (56%) were identified. Patient and disease characteristics are outlined in Table 1. With a median follow up of 42 (range, 1-232) months, the median PFS and OS for all study patients were 16 and 49 months, respectively, with respective 4-year PFS and OS estimates of 26% and 52%. Fifty-nine (54%) of patients died during the study period. All variables listed in Table 1 were assessed in UVA. Among those factors, age<65, achieving CR to frontline therapy, and receipt of upfront stem cell transplantation (SCT) were associated with improved PFS and OS. The respective 4-year PFS for age <65 vs ≥65 for achieving CR to frontline therapy were 39% and 13% (p=0.0165), vs no CR were 34% and 6% (p<0.0001); the PFS for receipt of upfront SCT vs no SCT vs SCT for relapsed AITL were 57%, 19%, and 0% (p<0.0001) (Figure 1A-C). The respective 4-year OS for age <65 vs ≥65 were of 68% and 38% (p=0.0011), for achieving CR to frontline therapy vs no CR were 61% and 37% (p<0.0001), and for receipt of upfront SCT vs no SCT were 85% and 41% (p=0.0137). A subgroup analysis was performed for 73 patients with available data on CD30 staining. We found a trend for improved OS for patients with positive CD30 (4-year OS 60% vs 30% for negative CD30; p=0.07 (Figure 1D). In MVA we included variables with p<0.15 significance in UVA and excluded Stage I-II disease and CD30 status given small number and missing values, respectively. In MVA, age ≥65 (HR 2.563, 95% CI: 1.419-4.628; p=0.0018), not achieving CR (HR 6.113, 95% CI: 3.048-12.258; p<0.0001), not receiving upfront SCT (HR 2.204, 95% CI: 1.125-4.317; p=0.0212) were associated with worse PFS. Similarly, age ≥65 (HR 2.339, 95% CI: 1.214-4.509; p=0.0111), not achieving CR (HR 2.533, 95% CI: 1.24-5.174; p=0.0107), and not receiving upfront SCT (HR 2.395, 95% CI: 1.009-5.688; p=0.0477) were associated with inferior OS in MVA.
Conclusions: Age <65 years, achieving CR to induction treatment, and upfront autologous SCT are strong predictors for improved PFS and OS. Further, we identified the potential prognostic role for CD30 status, for better OS. Upfront consolidation with SCT improves survival, however as majority of patients with AITL may not be transplant-eligible, it is imperative that novel therapies that disrupt the distinct biology be explored. Additional studies exploring additional prognostic markers will be provided at the annual meeting.
Parmar:Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Nastoupil:Pfizer: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Celgene: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Bayer: Honoraria; LAM Therapeutics: Research Funding; Janssen: Honoraria, Research Funding; Gamida Cell: Honoraria; Merck: Research Funding; Novartis: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; Gilead/KITE: Honoraria. Nieto:Affimed: Consultancy, Other: Grant Support; Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support; Secura Bio: Other: Grant Support. Hosing:NKARTA Inc.: Consultancy. Lee:Takeda: Research Funding; Oncternal Therapeutics: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding; Guidepoint Blogal: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Aptitude Health: Speakers Bureau. Westin:Novartis: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Amgen: Consultancy; Janssen: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Curis: Consultancy, Research Funding; 47: Research Funding; Genentech: Consultancy, Research Funding. Champlin:Actinium: Consultancy; Takeda: Patents & Royalties; Johnson and Johnson: Consultancy; Genzyme: Speakers Bureau; Omeros: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Cytonus: Consultancy. Khouri:Bristol Myers Squibb: Research Funding; Pfizer: Research Funding. Wang:Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Nobel Insights: Consultancy; Dava Oncology: Honoraria; Pulse Biosciences: Consultancy; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; Loxo Oncology: Consultancy, Research Funding; Targeted Oncology: Honoraria; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Guidepoint Global: Consultancy; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Juno: Consultancy, Research Funding; BioInvent: Research Funding; VelosBio: Research Funding; Acerta Pharma: Research Funding; InnoCare: Consultancy; Oncternal: Consultancy, Research Funding; Verastem: Research Funding; Molecular Templates: Research Funding; OncLive: Honoraria; Beijing Medical Award Foundation: Honoraria; Lu Daopei Medical Group: Honoraria; OMI: Honoraria, Other: Travel, accommodation, expenses; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding. Vega:NCI: Research Funding. Neelapu:Celgene: Other: personal fees, Research Funding; Novartis: Other: personal fees; Pfizer: Other: personal fees; Bristol-Myers Squibb: Other: personal fees, Research Funding; Legend Biotech: Other; Precision Biosciences: Other: personal fees, Research Funding; Adicet Bio: Other; Calibr: Other; Cell Medica/Kuur: Other: personal fees; Cellectis: Research Funding; Karus Therapeutics: Research Funding; Acerta: Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; N/A: Other; Unum Therapeutics: Other, Research Funding; Poseida: Research Funding; Takeda Pharmaceuticals: Patents & Royalties; Allogene Therapeutics: Other: personal fees, Research Funding; Incyte: Other: personal fees. Flowers:National Cancer Institute: Research Funding; Kite: Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; Eastern Cooperative Oncology Group: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; AbbVie: Consultancy, Research Funding; Bayer: Consultancy; Burroughs Wellcome Fund: Research Funding; TG Therapeutics: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Gilead: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; BeiGene: Consultancy; V Foundation: Research Funding. Iyer:Spectrum: Research Funding; Merck: Research Funding; Target Oncology: Honoraria; Afffimed: Research Funding; Seattle Genetics, Inc.: Research Funding; Rhizen: Research Funding; CRISPR: Research Funding; Trillium: Research Funding; Daiichi Sankyo: Consultancy; Curio Biosciences: Honoraria; Legend Biotech: Consultancy.
