Abstract: INTRODUCTION: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of lymphomas classically treated with CHOP or CHOP-like regimens, with poor outcomes. CD30 is universally expressed and is pathognomonic in systemic anaplastic large cell lymphoma (sALCL), with variable expression among non-sALCL PTCL subtypes (40-60%). Recent data of frontline treatment with Brentuximab Vedotin (BV), an anti-CD30 monoclonal antibody, plus CHOP has demonstrated significant improvement in survival (ECHELON-2 clinical trial), becoming the new standard of care for sALCL in Europe. PATIENT AND METHODS: From February 2019 to April 2021, 21 patients with de novo newly diagnosed CD30+ PTCL have been treated with the combination of BV-CHP, in the centers of the Catalan Institute of Oncology in Spain. Survival curves were plotted by the Kaplan-Meier method. RESULTS: Clinical characteristics at diagnosis are shown in the table. Of interest, 5 of the 11 ALK negative ALCL patients were diagnosed of breast implant associated ALCL (BIA-ALCL) with extracapsular involvement. The number of cycles administrated were 108, with a median of 6 cycles per patient (range 1-6), all of them with G-CSF primary prophylaxis. At the time of this report, 1 patient was still on treatment and 2 patients without the final evaluation. Seven cycles (6%) were delayed (3 due to infection, 2 due to neutropenia grade 2, and 2 due to causes not related with chemotherapy).An adverse event was reported in 45 (44%) cycles, being the most frequent peripheral neuropathy in 14, nausea/vomiting in 9 and anemia in 8; all of them grade 1-2. Treatment was discontinued after 1 cycle in 1 patient due to progression. Of the 18 evaluable patients, the overall response rate (ORR) was of 83%, with 72% complete responses and 11% partial responses. Consolidative autologous stem cell transplant (ASCT) was performed in 5 patients. With a median follow-up of 14 months (limits: 1-24), 1-year progression-free survival (PFS) and overall survival (OS) was 68.2% (95% CI 44.6-91.7) and 82.2% (95% CI 63.9-100), respectively. CONCLUSIONS: Brentuximab Vedotin plus CHP is an effective regimen for CD30 positive PTCL, with a high rate of response. This combination presents a manageable safety profile, with the majority of patients completing the planned treatment. The incidence and severity of side effects are low, being peripheral neuropathy and neutropenia the most frequent. Figure 1 Figure 1. Disclosures Eva: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sancho: Roche, Janssen, Celgene-BMS, Gilead, Novartis, Takeda: Honoraria, Speakers Bureau; Roche, Janssen, Celgene-BMS, Gilead, Novartis, Incyte, Beigene: Speakers Bureau. González-Barca: Janssen: Consultancy, Honoraria, Other: Travel; EUSA Pharma: Consultancy, Honoraria; Kyowa Kirin: Consultancy; Roche: Honoraria, Other: Travel; Takeda. Abbvie: Honoraria. Ribera: ARIAD: Consultancy, Research Funding, Speakers Bureau; SHIRE: Consultancy, Speakers Bureau; AMGEN: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; TAKEDA: Consultancy, Research Funding, Speakers Bureau; NOVARTIS: Consultancy, Speakers Bureau. Sureda: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bluebird: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Speakers Bureau; Roche: Other: Support for attending meetings and/or travel; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Mundipharma: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Abstract: The T-cell non-Hodgkin lymphomas continue to be an area of unmet need for new therapies that offer novel mechanisms of action. Tipifarnib is a potent and selective inhibitor of the enzyme farnesyltransferase (FT). Tipifarnib inhibits farnesylation of key regulatory proteins involved in CXCL12 production (Gualberto et al, EHA 2019). CXCL12 is a chemokine that is essential for T-cell homing to lymphoid organs and bone marrow, and for the maintenance of immune cell progenitors via its receptor CXCR4 (Susek et al, Front Immunology, 2018). Angioimmunoblastic T-cell lymphoma (AITL) is associated with high levels of CXCL12 expression, which is also a negative prognostic factor (Witzig et al, Blood, 2019). Additionally, Peripheral T-Cell lymphoma Not Otherwise Specified (PTCL-NOS) patients with the CXCL12 rs2839695 A/A wildtype genotype (PTCL-CXCL12+) have also been found to have elevated levels of CXCL12. Therefore, there is strong rationale for targeting these subsets of PTCL with tipifarnib. This Phase 2 study (NCT02464228) was a multi-institutional, single-arm, open-label trial determining the efficacy, safety, and potential predictive biomarkers for tipifarnib in adult patients with relapsed or refractory (R/R) PTCL. Patients received tipifarnib 300 mg orally twice daily on Days 1-21 of 28-day treatment cycles until progression of disease or unacceptable toxicity. The primary objective of the study was to determine the antitumor activity by overall response rate (ORR) per Lugano Classification. Secondary objectives included safety, duration of response (DoR) and progression-free survival (PFS), and exploratory analyses included overall survival (OS) and identification of potential biomarkers associated with tipifarnib activity. Sixty-five R/R PTCL patients (38 AITL, 14 PTCL-NOS, 11 PTCL-CXCL12+, 2 other (1 ALCL-ALK negative, 1 PTCL-subtype not specified) were treated with tipifarnib. The population was heavily pretreated with a median of 3 prior regimens (range 1-8). All patients had at least one treatment-emergent adverse event (TEAE); most patients (87.7%) had at least one treatment-related TEAE, and 18 (27.7%) patients had at least one treatment-related serious TEAE. The most frequently observed (≥20%) treatment-related TEAEs (all grades) were hematological (neutropenia, thrombocytopenia, anemia,) and gastrointestinal (nausea, diarrhea), as well as fatigue, which is consistent with the known safety profile of tipifarnib. Fifty-eight patients were efficacy evaluable and had an associated ORR of 39.7% (23/58) with most responses observed in the AITL and PTCL-CXCL12+ cohorts. In the 32 patients with AITL, the ORR was 56.3% (18/32), including 9 complete responses (CR) and 9 partial responses (PR). In the 10 patients with PTCL-CXCL12+, the ORR was 40.0% (4/10), including 1 CR and 3 PR. The median OS for patients with AITL was 32.8 months, and the median OS had not been reached for patients with PTCL-CXCL12+. Previously, a strong association between KIR3DL2 C336R/Q386E mutation and the activity of tipifarnib was observed and reported in AITL patients (Witzig et al, EHA 2020). Extensive gene expression and gene variant analyses of samples from the study population is currently ongoing to evaluate this correlation and explore other potential predictors of response. Final data will be presented at the time of the conference. Overall, the results from this Phase 2 study with tipifarnib demonstrated very encouraging efficacy in patients with CXCL12-expressing subtypes of PTCL (AITL and PTCL-CXCL12+) and showed a tolerable safety profile. Disclosures Witzig: Karyopharm Therapeutics, Abbvie/Genentech, Seattle Genetics, Celgene/BMS, Incyte, Epizyme, Cellectar, Tessa Therapeutics, Portola Pharmaceuticals, MorphoSys, ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Sokol: Dren Bio: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees. Kim: IGM Biosciences: Research Funding; Kyowa Kirin: Research Funding; Roche: Research Funding; Sanofi: Research Funding; Celltrion: Research Funding; Dong-A Pharmaceutical: Research Funding; Johnson & Johnson: Research Funding; Eisai: Research Funding. de la Cruz Vicente: 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; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Advani: Astellas/Agensys: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees; Cell Medica: Membership on an entity's Board of Directors or advisory committees; Forty Seven: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceutical: Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Kyowa: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Millenium: Research Funding; Pharmacyclics: Consultancy, Research Funding; Portola Pharmaceuticals: Consultancy; Regeneron: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees. Marin Niebla: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kiowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, 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; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau. Terol: BMS: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Hospital Clinico Valencia: Current Employment; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Roche: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding. Eva: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bendris: Kura Oncology: Current Employment, Current equity holder in publicly-traded company. Ahsan: Gilead: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Kura Oncology: Current Employment, Current equity holder in publicly-traded company. Leoni: Kura Oncology: Current Employment. Foss: Daiichi Sankyo: Honoraria; Mallinckrodt: Honoraria; Acrotech: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Kyowa: Honoraria; Kura: Honoraria.

Abstract: Introduction. Patients with relapsed/refractory classical Hodgkin's lymphoma (RRHL) still represent a therapeutic challenge. Consolidation with autologous stem cell transplantation (auto-HCT) is the standard of care in this setting. The achievement of a metabolic complete remission (mCR) with salvage chemotherapy (CT) improves long-term outcome after auto-HCT. The introduction of new drugs has significantly changed the landscape of RRHL. Our cooperative group (GELTAMO) has already demonstrated that brentuximab vedotin (BV) + ESHAP (BRESHAP, García-Sanz R et al, Ann Oncol 2019) is able to achieve a mCR rate of 70% before auto-HCT in patients with RRHL. Nevertheless, the superiority of BV + CT vs CT alone has never been tested in prospective randomized clinical trials. Additionally, it is unknown if consolidation treatment with BV could eventually spare auto-HCT in a good risk group of RRHL patients. Objectives. We have conducted a phase IIb prospective clinical trial (BRESELIBET, ClinicalTrials.gov ID: NCT04378647) that evaluates the efficacy of salvage therapy with BRESHAP vs ESHAP in patients with RRHL, followed by BV consolidation (instead of auto-HCT) in those who attained a mCR after salvage therapy. Methods. 150 adult patients with classical RRHL after one line of therapy were to be included and randomized 1:1 in an open label design to receive either BRESHAP [BV (1.8 mg/m 2 iv, D1), etoposide (40 mg/m 2/day iv, D1-4), Solumedrol (250 mg/day iv, D1-4), Ara-C (2 g/m 2 iv, D5) and cisplatin (25 mg/m 2/day iv, D1-4)] (x3 cycles) or ESHAP (x3 cycles). Primary efficacy endpoint of the trial was mCR [Deauville Score (DS) of 1-2] . Those patients in mCR went on to receive up to a 16 doses of BV (1.8 mg/kg iv every 3 weeks) unless unacceptable toxicity or disease progression. Patients not achieving a mCR went off the trial. Herein we are reporting preliminary results of the first 43 patients treated within the trial. Results. As of June 2021, 47 patients have been enrolled; 3 of them have been screening failures and one patient is still under screening. Among the remaining 43 patients [28 males, age at inclusion of 42 (18-64) years, median (range)] , 15 were primary refractory, 15 had an early relapse (1 st CR & lt;12 months) and 13 a late relapse (1 st CR ≥12 months). Twenty-two patients were randomized into the BRESHAP arm and 21 into the ESHAP arm. There were no significant clinical differences at inclusion between both arms. Twenty-nine patients have completed salvage therapy and have had their disease status evaluated, 1 patient was discontinued from the trial because of an adverse event (AE) during second line therapy (BRESHAP arm), 2 patients progressed under therapy (both of them assigned to the BRESHAP arm) and 11 patients are still under treatment. Twelve patients (5 BRESHAP; 7 ESHAP) achieved a mCR as defined in the trial (41.3%, NS between both arms). All of them have started consolidation with BV; after a median of 4 (1-12) cycles, only one patient assigned to the BRESHAP arm has relapsed after the 3 rd cycle. 17 patients' disease did not achieve a mCR and discontinued treatment on the trial: 6 were DS3, 2 DS4 and 9 DS5. All patients with DS3 after salvage treatment were subsequently consolidated with auto-HCT off trial and are in continuous CR. Nine severe AEs were reported in 7 patients [fever (n=3), sepsis (n=2), pneumonia (n=1), pericardial effusion (n=1), diarrhea (n=1), vomiting (n=1)]. Grade 3-4 hematological toxicity was seen in 13 cases: neutropenia (n=9), thrombocytopenia (n=8) and anemia (n=7) with only 4 cases of grade 3-4 infectious episodes. Grade 3-4 non-hematological AE (≥5% of cases) were hypomagnesemia (n=2) and non-neutropenia fever (n=1). No treatment related deaths have been reported. Conclusions. BRESELIBET trial is a randomized trial that tries to demonstrate the superiority of BRESHAP vs ESHAP in RRHL as well as the feasibility of a non-transplant option in patients achieving a stringent CR assessed by PET-CT. These initial results provide safety data as possible support for these two hypotheses and the trial enrollment continues. Disclosures Sureda: Takeda: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Honoraria; Mundipharma: Consultancy. Núñez: Tekada: Consultancy; Incyte: Consultancy. De la Cruz: Abbvie: 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; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; JANSSEN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirkin: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Eva: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Terol: Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Roche: Consultancy; BMS: Consultancy; Hospital Clinico Valencia: Current Employment. Cordoba: ADCTherapeutics: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees; AbbVie: 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; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: 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; Incyte: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding. Greil: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Daiichi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Sandoz: Honoraria, Research Funding. Romero: Takeda: Honoraria; Alexion: Honoraria.

Abstract: Introduction The phase 3 ECHELON-2 study (NCT01777152) compared frontline treatment with brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for patients (pts) with systemic anaplastic large cell lymphoma (sALCL) or other CD30+ peripheral T-cell lymphomas (PTCL). At 5 years, A+CHP continues to provide clinically meaningful improvement in progression-free survival (PFS) (hazard ratio [HR] 0.70 [95% confidence interval {CI}: 0.53, 0.91] , P=0.0077) and overall survival (OS) (HR 0.72 [95% CI: 0.53, 0.99], P=0.0424) vs CHOP. Ongoing remission was observed in ~60% of pts with sALCL, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy (Horwitz S, et al. ASH 2020). Due to the rarity of this disease and lack of data on prospective, uniformly treated pts, ECHELON-2 provides a large and unique prospective data set with potential utility in informing future studies of PTCL. Herein, we report a series of exploratory analyses in prespecified subgroups based on age, gender, and histology to supplement the data from the full 5-year analysis. Methods ECHELON-2 (N=452) is a randomized, double-blind, double-dummy, placebo-controlled, multicenter study. Eligible pts with previously untreated CD30+ PTCL were randomized 1:1 to A+CHP or CHOP for 6 or 8 cycles. Randomization was stratified by histological subtype and international prognostic index (IPI) score. The primary endpoint of PFS was assessed per blinded independent central review in the primary analysis and per investigator in this exploratory subgroup analysis. Outcomes by age & lt;60 and ≥60 years, gender, and PTCL subtype (PTCL-not otherwise specified [NOS], angioimmunoblastic T-cell lymphoma [AITL] , and sALCL by IPI categories) were assessed. ECHELON-2 was not powered or designed to compare efficacy of therapy within individual histologic subtypes other than sALCL or other baseline characteristics. Results Among all pts & lt;60, the median PFS was not reached versus vs 17.48 months among all pts ≥60. When assessing by treatment, PFS favored A+CHP vs CHOP for both age groups (Table 1). PFS outcomes in the & lt;60 subgroup were superior vs the ≥60 subgroup in both arms (Table 2). In addition, the median OS for those & lt;60 was not reached vs 60.4 months for those ≥60. OS was also longer in those treated with A+CHP regardless of age ( & lt;60, HR 0.66 [95% CI: 0.38, 1.15], P=0.1402; ≥60, HR 0.73 [95% CI: 0.49, 1.07] , P=0.1054).Within each arm, OS was superior in the & lt;60 vs ≥60 age group (A+CHP, HR 0.54 [95% CI: 0.31, 0.93], P=0.0252; CHOP, HR 0.44 [95% CI: 0.27, 0.72] , P=0.0008). The potential association of gender with PFS outcomes varied within each treatment arm: males on the CHOP arm had higher PFS than females while females had higher PFS than males on the A+CHP arm (Table 2). In addition, the OS benefit of A+CHP vs CHOP was consistent for both genders (female, HR 0.68 [95% CI: 0.40, 1.16], P=0.1597; male, HR 0.73 [95% CI: 0.49, 1.08] , P=0.1148). Females and males had similar OS within each arm (A+CHP, female vs male: HR 1.00 [95% CI: 0.61, 1.64], P=0.9966; CHOP, female vs male: HR 1.03 [95% CI: 0.66, 1.60] , P=0. 9054). Among all pts with PTCL-NOS, the median PFS and OS were 13.57 months and 46.4 months. When assessing by treatment arm, the PFS (Table 1) and OS (HR 0.75 [95% CI: 0.37, 1.48], P=0.4003) HRs were similar to the intent-to-treat (ITT) population. Among all pts with AITL, the median PFS was 23.75 months and the median OS was not reached. When assessing by treatment arm, the PFS (Table 1) favored CHOP and OS was similar (HR 1.01 [95% CI: 0.40, 2.55] , P=0.9855). In the sALCL subgroup, PFS was superior in those treated with A+CHP overall and across IPI subgroups: 0-1, 2-3, 4-5 (Table 1). OS was also longer in the A+CHP arm (HR 0.66 [95% CI: 0.43, 1.01] , P=0.0529) overall and across IPI subgroups: 0-1 (HR 0.73 [95% CI: 0.20, 2.73], P=0.6411), 2-3 (HR 0.57 [95% CI: 0.32, 1.01] , P=0.0496), and 4-5 (HR 0.89 [95% CI: 0.42, 1.89], P=0.7606). Conclusions ECHELON-2 results at 5 years demonstrate a generally consistent benefit of A+CHP over CHOP across subgroups and for the ITT population. Furthermore, this large prospective dataset of pts with PTCL has redefined efficacy outcomes for this population and provides important benchmark data to inform future studies. Figure 1 Figure 1. Disclosures Horwitz: Affimed: Research Funding; Acrotech Biopharma, Affimed, ADC Therapeutics, Astex, Merck, Portola Pharma, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle Genetics, Shoreline Biosciences, Inc, Takeda, Trillium Th: Consultancy; ADC Therapeutics, Affimed, Aileron, Celgene, Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium /Takeda, Seattle Genetics, Trillium Therapeutics, and Verastem/SecuraBio.: Consultancy, Research Funding; Aileron: Research Funding; Celgene: Research Funding; C4 Therapeutics: Consultancy; Crispr Therapeutics: Research Funding; Daiichi Sankyo: Research Funding; Forty Seven, Inc.: Research Funding; Kura Oncology: Consultancy; Kyowa Hakko Kirin: Consultancy, Research Funding; Millennium/Takeda: Research Funding; Myeloid Therapeutics: Consultancy; ONO Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Research Funding; Secura Bio: Consultancy; Shoreline Biosciences, Inc.: Consultancy; Takeda: Consultancy; Trillium Therapeutics: Consultancy, Research Funding; Tubulis: Consultancy; Verastem/Securabio: Research Funding. Savage: Astra-Zeneca: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Takeda: Other: Institutional clinical trial funding; AbbVie: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Seattle Genetics: Consultancy, Honoraria; Roche: Research Funding; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding. Illidge: Seagen Inc.: Research Funding. Advani: Astellas/Agensys: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees; Cell Medica: Membership on an entity's Board of Directors or advisory committees; Forty Seven: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceutical: Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Kyowa: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Millenium: Research Funding; Pharmacyclics: Consultancy, Research Funding; Portola Pharmaceuticals: Consultancy; Regeneron: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees. Shustov: Seagen Inc.: Research Funding. Bartlett: Pharmacyclics: Research Funding; Millennium: Research Funding; Merck: Research Funding; Kite, a Gilead Company: Research Funding; Janssen: Research Funding; Genentech: Research Funding; Forty Seven: Research Funding; Celgene: Research Funding; Bristol Myers Squibb: Research Funding; Autolus: Research Funding; Seagen: Consultancy, Research Funding; Roche/Genentech: Consultancy; ADC Therapeutics: Consultancy, Research Funding. Jacobsen: Takeda: Consultancy; Syros: Consultancy; Janssen: Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding. Koch: Seagen Inc.: Research Funding. Eva: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Fanale: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Fenton: Seagen Inc.: Current Employment, Current equity holder in publicly-traded company. Campana: Seagen Inc.: Research Funding. Dong: Seagen Inc.: Research Funding. Truemper: Seagen Inc.: Research Funding.