Background: Peripheral T-cell lymphomas (PTCLs) are uncommon, heterogeneous, and often aggressive subtypes of lymphoma characterized by a high risk of progression even after combination chemotherapy. The phase III, ECHELON-2 trial showed that the combination of brentuximab vedotin with chemotherapy (A+CHP) in patients (pts) with CD30-positive PTCLs improved progression-free survival (PFS) and overall survival (OS) compared to CHOP. In PTCL, positron emission tomography (PET) is a valuable way to assess disease burden and stage at the time of diagnosis and evaluate treatment response. Prior retrospective studies have shown that interim and end of treatment PET may predict outcomes; however, there are no prospective studies confirming their predictive value. In the ECHELON-2 study, PET4 outcomes were prospectively collected, and the objective of this exploratory analysis is to investigate the potential for interim PET scans to predict treatment response and long-term outcomes.

Objective: To evaluate the role of interim 18F-FDG PET imaging (PET4) in predicting end of treatment (EOT) response, progression free survival (PFS), and overall survival (OS) in pts (pts) with CD30+PTCL treated with A+CHP or CHOP in the ECHELON-2 trial.

Methods: The ECHELON-2 trial included prospective 18F-FDG PET scans and assessment of treatment response including long-term PFS per investigator and OS. PET4 status was based on Deauville score by Independent Review Facility (IRF) assessment using scans at the cycle 4 response assessment. Deauville scores 1-3 are considered negative (PET4neg) and 4-5 positive (PET4pos). EOT response is the best response after completion of study treatment and prior to long term follow up per Cheson 2007 by IRF assessment. Kaplan-Meier methods were used to estimate PFS and OS; p-values are based on stratified log-rank tests. All analyses are exploratory, and p-values are descriptive.

Results: In this study, 452 pts were included, with 226 randomized to the A+CHP treatment arm and 226 to the CHOP treatment arm; median follow up was 66.8 months (range 0-90). Of randomized pts, 32 pts in the A+CHP arm and 41 pts in the CHOP arm were not evaluable for PET4. The overall results showed that the PET4neg evaluable subgroup had a higher proportion of pts achieving complete responses (CR) than PET4pos (80% vs. 9%) at EOT (Table 1). In pts assessed for PET4, pts who were PET4neg had improved PFS and OS in both the A+CHP and CHOP treatment arms (Figure 1). For A+CHP pts, those who achieved PET4neg had an improved PFS [HR 0.36, CI-95 (0.19-0.66), p=0.0006] and OS [HR 0.38, CI-95 (0.18-0.78), p=0.0060] compared to those who were PET4pos. Similarly, pts in the CHOP arm who achieved PET4neg had an improved PFS [HR 0.26, CI-95 (0.17-0.41), p<0.0001] and OS [HR 0.24, CI-95 (0.14-0.41), p< 0.0001] compared to those who were PET4pos. Among pts with anaplastic large cell lymphoma (sALCL) (n=316), 19 pts in the A+CHP arm and 32 in the CHOP arm were not evaluable for PET4. The results in this subgroup show that 128/143 (90%) A+CHP pts who had PET4 assessments achieved PET4neg. These pts experienced improved PFS [HR 0.28, CI-95 (0.14-0.60), p=0.0004] and OS [HR 0.38, CI-95 (0.16-0.94), p 0.0292] compared to PET4pos pts. For CHOP pts who had PET4 assessments 98/122 (80%), achieved PET4neg; these pts experienced improved PFS [HR 0.31, CI-95 (0.12-0.55), p<0.0001] and improved OS [HR 0.25, CI-95 (0.12-0.25), p= 0.0002] compared to PET4pos pts.

Conclusion: In an exploratory analysis of interim PET imaging as part of the ECHELON-2 study, PET4neg by Deauville was associated with improved PFS and OS in both the A+CHP and CHOP arms. Our findings support the use of PET4 response in PTCL as a predictor of outcomes in both the A+CHP and CHOP pts. These findings emphasize the potential of PET scans to enhance risk stratification, individualize therapy decisions, and improve pt outcomes in the management of PTCLs. Further analysis will be presented at the meeting.

Iyer:Yingli: Consultancy, Research Funding; CRISPR: Consultancy, Research Funding; Innate: Research Funding; Acrotech: Consultancy, Research Funding; Legend: Research Funding; Astra Zeneca: Research Funding; Ono: Research Funding; Pfizer: Research Funding; Salarius: Consultancy; Drenbio: Research Funding; Merck: Research Funding; American Society of Transplant and Cellular Therapy: Speakers Bureau; CuraBio: Speakers Bureau; American Society of Hematology: Speakers Bureau; Seagen: Consultancy, Research Funding. Mehta-Shah:Corvus Pharmaceuticals: Research Funding; Ono Pharmaceuticals: Consultancy; Karyopharm Therapeutics: Consultancy; Secura Bio/Verastem: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Bristol Myers-Squibb: Research Funding; Celgene: Research Funding; C4 Therapeutics: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Genentech: Consultancy; Genentech/Roche: Research Funding; Innate Pharmaceuticals: Research Funding; Kyowa Hakko: Consultancy; Janssen: Consultancy. Advani:Genentech: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; ADCT: Membership on an entity's Board of Directors or advisory committees, Research Funding; Epizyme: Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding; Cyteir: Research Funding; Merck: Research Funding; Gilead: Research Funding; Seagen: Research Funding. Bartlett:ADC Therapeutics, Foresight Diagnostics, Kite, F. Hoffmann-La Roche Ltd / Genentech, Inc., Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics, Autolus, BMS/Celgene, Forty Seven, Gilead/Kite Pharma, Janssen, Merck, Millennium, Pharmacyclics, F. Hoffmann-La Roche Ltd / Genentech, Inc., Seattle Genetics: Research Funding; Washington University School of Medicine: Current Employment. Kim:Boryung: Research Funding; Beigene: Research Funding; Kyowa-Kirin: Research Funding; Roche: Research Funding; Donga: Research Funding; Sanofi: Research Funding. Feldman:Janssen: Research Funding; Takeda: Research Funding; Takeda: Speakers Bureau; Daiichi Sankyo: Research Funding; BMS: Research Funding; Corvus: Research Funding; AstraZeneca: Consultancy; Gilead: Consultancy; Seagen: Consultancy; Genmab: Research Funding; Tessa: Research Funding; Merck: Research Funding; AstraZeneca: Research Funding; Seagen: Research Funding; ADCT: Membership on an entity's Board of Directors or advisory committees; Seagen: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees; Epizyme: Speakers Bureau; Wyeth: Research Funding; Epizyme: Honoraria; KITE: Honoraria; Seagen: Honoraria; ADCT: Honoraria; Genomic Testing Cooperative: Current equity holder in private company; Kymera: Research Funding; Juno: Research Funding; Seagen: Speakers Bureau; ADCT: Consultancy; ADCT: Research Funding; Epizyme: Consultancy; Epizyme: Research Funding; AstraZeneca: Honoraria; Genmab: Consultancy; Genmab: Honoraria; BMS: Consultancy. Zinzani:ASTRAZENECA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SECURA BIO: Membership on an entity's Board of Directors or advisory committees; CELLTRION: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC THERAPEUTICS: Membership on an entity's Board of Directors or advisory committees; TAKEDA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; INCYTE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BEIGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rambaldi:Abbvie: Honoraria. Belada:Genmab: Research Funding; Morphosys: Consultancy; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mayer:BeiGene: Research Funding. Jain:Seagen: Current Employment, Current equity holder in publicly-traded company. Keenan:Seagen: Current Employment, Current equity holder in private company. Fanale:Seagen: Current Employment, Current equity holder in publicly-traded company. Savage:Roche: Research Funding; Seagen: Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Merck: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding. Horwitz:Trillium Therapeutics: Consultancy, Research Funding; ADC Therapeutics: Research Funding; Tubulis: Consultancy; ONO Pharmaceuticals: Consultancy; Auxilius Pharma: Consultancy; Abcuro Inc.: Consultancy; Daiichi Sankyo: Consultancy, Research Funding; Seattle Genetics: Research Funding; Cimieo Therapeutics: Consultancy; Celgene: Research Funding; Crispr Therapeutics: Research Funding; Shoreline Biosciences, Inc.: Consultancy; Kyowa Hakko Kirin: Consultancy, Research Funding; SecuraBio: Consultancy; Takeda: Consultancy, Research Funding; Yingli Pharma Limited: Consultancy; Millenium: Research Funding; Affimed: Research Funding; Verastem/SecuraBio: Research Funding.

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2023
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