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1591 Patterns of Care and Clinical Outcomes in Peripheral T-Cell Lymphomas: The Lymphoma Epidemiology of Outcomes (LEO) and Molecular Epidemiology Resource (LEO-MER) Prospective Cohort Study

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, adult, epidemiology, Lymphomas, health outcomes research, Clinical Research, T Cell lymphoma, Diseases, real-world evidence, Lymphoid Malignancies, Study Population, Human
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Jia Ruan, MD, PhD1, Melissa C. Larson, MS2*, Zhengming Chen, PhD, MPH1*, N. Nora Nora Bennani, MD3, Pamela B. Allen, MD4, David L. Jaye, MD5, Jonathon B. Cohen, MD, MS6, Dai Chihara, MD7, Francisco Vega, MD, PhD8, Giorgio Inghirami, MD9*, Eric Mou, MD10, Carla Casulo, MD11, Neha Mehta-Shah, MD, MSCI12, Peter Martin, FRCPC, MD, MS13, Matthew J. Maurer, DSc2, Brad S. Kahl, MD12, Izidore S. Lossos, MD14, Christopher R. Flowers, MD7, James R. Cerhan, MD, PhD2 and Andrew L. Feldman, MD15

1Meyer Cancer Center, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY
2Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN
3Division of Hematology, Mayo Clinic, Rochester, MN
4Winship Cancer Institute, Emory University, Atlanta, GA
5Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Dunwoody, GA
6Department of Hematology and Medical Oncology, Emory University, Atlanta, GA
7Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX
8Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
9Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
10Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA
11University of Rochester Medical Center, Rochester, NY
12Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
13Meyer Cancer Center, Weill Cornell Medical College-New York Presbyterian Hospital, New York, NY
14Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL
15Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN

Background

Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous group of non-Hodgkin lymphomas of mature T-cell origin. Systemic PTCL (sPTCL) has mostly poor outcomes with conventional (CHOP-like) chemotherapy. Biomarker-driven, subtype-specific and personalized treatments are promising but unmet needs. Few benchmark studies exist to delineate the contemporary landscape of clinical and pathologic practice in the real-world setting to guide therapeutic development. We report herein the patterns of care and outcomes for PTCL patients enrolled in the LEO-MER multi-center prospective cohort study.

Methods

Patients ≥ 18 years with newly diagnosed PTCL were prospectively enrolled in the University of Iowa/Mayo Clinic MER cohort (2002-2015) and the expanded 8 US center LEO cohort (2015-2020). Clinical, pathology, treatment, and outcome data were abstracted from medical records using a standard protocol. Pathology underwent expert re-review based on WHO criteria, with harmonization between the 2008 and 2016 classifications where appropriate. Overall survival (OS) was calculated from date of diagnosis to date of death or last follow-up. Event-free survival (EFS) was calculated from date of diagnosis to disease progression, initiation of 2nd line therapy, or death from any cause. EFS and OS were evaluated using Cox Model and Kaplan-Meier curves.

Results

1132 PTCL were identified (462 MER and 670 LEO), including 718 sPTCL (281 MER and 437 LEO). sPTCL subtypes included PTCL-NOS (N=252, 35.1%), anaplastic large cell lymphoma (ALCL; N=180, 25.7% [74 ALK+, 106 ALK-]), angioimmunoblastic T-cell lymphoma (AITL, N=162, 22.6%), extranodal NK-TCL (N=50, 7.0%), adult T-cell leukemia/lymphoma (N=32, 4.5%), enteropathy-associated TCL (N=19, 2.6%), and hepatosplenic TCL (N=13, 1.8%). Median age at diagnosis was 60 years. M:F ratio was 1.5. Comparing LEO to MER, nonwhite population was 23.8% vs 8.5%, and Hispanic was 10.1% vs 2.2%. Clinical characteristics were comparable between MER and LEO overall: PS≥2, 21.2%; elevated LDH, 50.4%; stage III-IV, 67.5%; and IPI 2-5, 61.6%.

The most common 1st line chemotherapy regimens were anthracycline-based (N=514, 72.2%), of which 205 (39.9%) included etoposide (50 [24.4%] in MER, 155 [50.2%] in LEO) and 43 (8.4%) included brentuximab vedotin (0 in MER and 43 [13.9%] in LEO). 73 patients (10.3%) underwent consolidative SCT following induction chemotherapy (70 auto and 3 allo), and 64 patients (11.1%) received frontline therapy on clinical trials. At a median follow-up of 9.3 years (95% CI: 8.9-10.8) in MER and 3.2 years (95% CI: 3.1-3.6) in LEO, 177 (MER) and 250 (LEO) events, and 150 (MER) and 183 (LEO) deaths were observed, respectively. The 2-year EFS and 3-year OS estimates for sPTCL were 51.6% (95% CI: 46.0%-57.8%) and 61.3% (95% CI: 55.9%-67.3%) in MER, and 45.6% (95% CI: 41.0%-50.7%) and 58.4%% (95% CI: 53.6%-63.6%) in LEO. EFS and OS correlated with IPI scores and differed by sPTCL subtypes. ALCL has superior survival, with 2-year EFS and 3-year OS of 79.0% (95% CI: 70.0%-89.0%) and 90.5% (95% CI: 84.0%-97.4%) for ALK+ and 69.4% (95% CI: 60.9%-79.0%) and 79.4% (95% CI: 71.7%-87.9%) for ALK-. Non-ALCL subtypes including PTCL-NOS and AITL have inferior outcomes, with 2-year EFS and 3-year OS of 38.9% (95% CI: 33.3%-45.4%) and 47.3% (95% CI: 41.4%-54.0%) for PTCL-NOS, and 36.2% (95% CI: 29.3%-44.7%) and 57.3% for AITL (95% CI: 49.8%-65.9%).

Conclusion

The MER-LEO study is the largest prospective cohort study to date for PTCL in the contemporary era and continues to mature with longitudinal follow-up and ongoing accrual. In comparison to MER, the LEO cohort better reflects the US demographic diversity and begins to incorporate novel agents such as BV in frontline therapy, while most patients in both cohorts continue to receive CHOP-based induction chemotherapy. The overall stability of clinical outcomes within the consecutive MER and LEO cohorts underscores the unmet need of therapeutic breakthrough on a real-world population basis within the past 2 decades, where clinical trials with biomarker-driven targeted approach for non-ALCL frontline treatment are in great need (ClinicalTrials.gov NCT02736357).

Disclosures: Ruan: Pharmacyclics: Research Funding; Kite Pharma: Consultancy; Daiichi Sankyo: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy; AstraZeneca: Research Funding; Genentech: Research Funding. Allen: Kyowa: Consultancy, Honoraria; Daiichi Sanyko: Consultancy, Honoraria. Cohen: Aptitude Health: Consultancy; Lilly Oncology/Eli Lilly: Consultancy, Research Funding; Astrazeneca: Consultancy, Research Funding; Novartis: Research Funding; Takeda: Research Funding; BeiGene: Consultancy, Research Funding; Genentech: Research Funding; HutchMed: Consultancy, Research Funding; Janssen: Consultancy; Kite Pharma/Gilead: Consultancy; BMS/Celgene: Research Funding. Vega: Crisp Therapeutics: Research Funding; Allogene: Research Funding; Geron Corporation: Research Funding. Casulo: Bristol Myers Squibb: Research Funding; Secura Bio: Research Funding; Verastem: Research Funding; Gilead: Research Funding; Genentech: Research Funding. Mehta-Shah: Genetech/Roch: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Corvus Pharmaceuticals: Research Funding; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers-Squibb: Research Funding; Secura Bio: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Hakko Kirin Co., Ltd.: Membership on an entity's Board of Directors or advisory committees; Verastem: Research Funding. Martin: ADCT: Consultancy; AstraZeneca: Consultancy; Beigene: Consultancy; BMS: Consultancy; Daiichi Sankyo: Consultancy; Epizyme: Consultancy; Genentech: Consultancy; Janssen: Consultancy; Regeneron: Consultancy; Takeda: Consultancy. Maurer: Roche/Genentech: Research Funding; Morphosys: Research Funding; GenMab: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Kahl: AcertaPharma: Consultancy; MEI: Consultancy; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Roche: Consultancy; ADT Therapeutics: Consultancy; AstraZeneca: Consultancy, Research Funding; Pharmacyclics: Consultancy; Celgene/BMS: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Kite: Consultancy; Janssen: Consultancy; Incyte: Consultancy; Hutchmed: Consultancy, Research Funding; TG Therapeutics: Consultancy; Genmab: Consultancy; Seattle Genetics: Consultancy; Research To Practice: Speakers Bureau. Lossos: Adaptive: Honoraria; NCI: Research Funding; LRF: Membership on an entity's Board of Directors or advisory committees. Flowers: Xencor: Research Funding; Ziopharm: Research Funding; Adaptimmune: Research Funding; Amgen: Research Funding; Abbvie: Consultancy, Research Funding; Karyopharm: Consultancy; Gilead: Consultancy, Research Funding; Spectrum: Consultancy; 4D: Research Funding; NPower: Current holder of stock options in a privately-held company; Allogene: Research Funding; Sanofi: Research Funding; Kite: Research Funding; Pharmacyclics: Research Funding; Pfizer: Research Funding; Morphosys: Research Funding; Iovance: Research Funding; Janssen Pharmaceutical: Research Funding; Pharmacyclics/Janssen: Consultancy; Acerta: Research Funding; Cellectis: Research Funding; EMD: Research Funding; Guardant: Research Funding; SeaGen: Consultancy; TG Therapeutics: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; Takeda: Research Funding; Genmab: Consultancy; Bayer: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; BeiGene: Consultancy; V Foundation, Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding. Cerhan: NanoString: Research Funding; GenMab: Research Funding; Genentech: Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Protagonist: Membership on an entity's Board of Directors or advisory committees.

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