-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

4483 Outcomes in Older Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) from the ECHELON-3 Study

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical trials, Combination therapy, Elderly, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Diseases, Treatment Considerations, Lymphoid Malignancies, Human, Study Population
Monday, December 9, 2024, 6:00 PM-8:00 PM

Nancy L. Bartlett, MD1, Jeong-A Kim2, Uwe Hahn3*, Isabelle Fleury, MD, MSc4, Kamel Laribi5*, Juan Miguel Bergua Burgues, MD6*, Craig A. Portell7*, Melina Boutin8*, Blanca Sanchez Gonzalez9*, Selay Lam10*, Sung Yong Oh11*, Judit Mészáros Joergensen, MD, PhD12*, Young Rok Do, MD, PhD13, Herve Ghesquieres, MD, PhD14*, Grzegorz S. Nowakowski, MD15, Christopher Yasenchak, MD16, Monica Patterson17*, Linda Ho17*, Evelyn Rustia17*, Michelle Fanale18*, Keenan Fenton17* and Vincent Ribrag, MD19

1Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
2St. Vincent Hospital, The Catholic University of Korea, Suwon, South Korea
3Royal Adelaide Hospital, Adelaide, Australia
4CIUSSS de L'Est de l'lle de Montreal / installation Hopital Maisonneuve-Rosemont, Montreal, QC, Canada
5Hématologie Clinique, CH Le Mans, Le Mans, France
6Hospital San Pedro de Alcántara, Caceres, Spain
7UVA Comprehensive Cancer Center, University of Virginia, Charlottesville, VA
8CISSS de la Monteregie-Centre, Longueuil, QC, CAN
9Hematology Department, Hospital del Mar, Barcelona, Spain
10London Health Sciences Centre - Victoria Hospital, London, Canada
11Dong-A University Hospital, Busan, Korea, Republic of (South)
12Aarhus University Hospital, Aarhus, Ethiopia
13Department of Hemato-Oncology, Dongsan Medical Center, Keimyung University, Daegu, Korea, Republic of (South)
14Department of Hematology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France
15Mayo Clinic, Rochester, MN
16Willamette Valley Cancer Institute and Research Center/US Oncology Research, Eugene, OR
17Pfizer Inc., Bothell, WA
18Pfizer, New York, NY
19Institut Gustave Roussy, Villejuif, France

Introduction

Age correlates with survival in patients (pts) with DLBCL, which has a median age at diagnosis of 67 y. Recent therapeutic advances, including bispecifics and cell therapy, have promising efficacy, but safety and accessibility continue to be limited for older pts. The randomized, global, phase 3 ECHELON-3 study (NCT04404283) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) with brentuximab vedotin (BV) + lenalidomide (Len) + rituximab (R; BV+Len+R) vs placebo+Len+R in pts with R/R DLBCL after ≥ 2 prior systemic therapies who were ineligible for hematopoietic stem cell transplant and/or chimeric antigen receptor (CAR) T-cell therapy. Here, we present safety and efficacy in pts aged ≥65 y.

Methods

In ECHELON-3, pts were randomized 1:1 to receive BV (1.2 mg/kg) or placebo every 3 weeks (q3w), in combination with R (375 mg/m2) q3w and Len (20 mg) once daily. Granulocyte colony-stimulating factor was required in all cycles. Efficacy was assessed by investigators per Lugano 2014 classification. The primary endpoint was OS, with key secondary endpoints of PFS and ORR. Other secondary endpoints included detailed safety and tolerability. This subgroup analysis comprises pts aged ≥65 y. P values are descriptive.

Results

A total of 155 pts aged ≥65 y were enrolled from April 2021 to November 2023 and randomized to BV+Len+R (n=79) or placebo+Len+R (n=76). The median age was 75 y (range, 65-89 y); 54% of pts were male, 59% were White, and 19% were Asian. Twenty-three percent and 54% had Ann Arbor stage III and IV disease, respectively, and 64% had high-intermediate or high International Prognostic Index scores (3-5) at enrollment. The most common DLBCL subtype was DLBCL not otherwise specified (58%). Twenty-nine percent of pts had transformed DLBCL. Approximately half (49%) of pts had primary refractory disease, and 81% had disease refractory to their most recent prior line of therapy. Seventy percent of pts had <1% CD30 expression via IHC; 48% of cases had germinal center B-cell origin. Prior CAR-T was reported in 21.9% of pts.

At a median follow-up of 16.8 mo (95% CI, 14.3-19.5 mo), median OS was 15.9 mo (95% CI, 11.7 mo-not estimable [NE]) with BV+Len+R vs 8.5 mo (95% CI, 5.5-11.5 mo) with placebo+Len+R (hazard ratio [HR], 0.540; 95% CI, 0.351-0.830; P=.0043). Median PFS was 5.7 mo (95% CI, 4.1-12.7 mo) with BV+Len+R vs 2.8 mo (95% CI, 1.9-4.1 mo) with placebo+Len+R (HR, 0.478; 95% CI, 0.318-0.718; P=.0003). ORR was 70.9% (95% CI, 59.6%-80.6%) with BV+Len+R vs 46.1% (95% CI, 34.5%-57.9%) with placebo+Len+R (P=.0020); complete response (CR) rate was 45.6% vs 19.7%, respectively. Median time to CR was 1.61 mo with both BV+Len+R and placebo+Len+R (range, 1.2-7.3 vs 0.7-4.6 mo, respectively). Median duration of CR was 18.9 mo (95% CI, 12.4 mo-NE) with BV+Len+R vs 5.4 mo (95% CI, 2.8 mo-NE) with placebo+Len+R (HR, 0.416; 95% CI, 0.139-1.250).

In total, 154 pts were evaluable for safety analysis (75 pts in placebo+Len+R group). The median number of cycles was 5 (range, 1-34) vs 3 (range, 1-31) in the BV+Len+R and placebo+Len+R groups, respectively. The percentage of pts with any treatment-emergent adverse event (TEAE) was similar between groups (97% with BV+Len+R and 99% with placebo+Len+R); grade ≥3 TEAEs occurred in 89% of pts in the BV+Len+R group and 76% in the placebo+Len+R group. Serious TEAEs and TEAEs leading to death were reported more frequently in the BV+Len+R group (62% and 13%, respectively) than the placebo+Len+R group (47% and 8%, respectively). More pts discontinued study treatment due to TEAEs in the BV+Len+R group than the placebo+Len+R group (20% vs 8%). In total, 39% of pts on BV+Len+R had a peripheral neuropathy event vs 27% of pts on placebo+Len+R; however, the majority of cases were grade 1 (22% and 17%, respectively). Additional information on older pts will be presented.

Conclusions

BV+Len+R demonstrated a clinically meaningful improvement in all key efficacy outcomes in pts aged ≥65 y, which is consistent with the overall ECHELON-3 population (median age 74 y; 70.5% of pts aged ≥65 y in BV+Len+R group). Differences in some safety endpoints are likely attributable to longer duration of treatment in the BV+Len+R group. No clinically meaningful safety trends in pts aged ≥65 y were identified. These results suggest that BV+Len+R may be an effective treatment option in older pts with R/R DLBCL.

Disclosures: Bartlett: Genmab: Membership on an entity's Board of Directors or advisory committees, Research Funding; Foresight Diagnostics: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Millennium: Research Funding; Janssen: Research Funding; Kite Pharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Forty Seven: Research Funding; Celegne: Research Funding; BMS: Research Funding; Autolus: Research Funding; ADC Therapeutics: Research Funding; Washington University School of Medicine: Current Employment. Kim: St. Vincent’s Hospital, The Catholic University of Korea, Suwon, South Korea: Current Employment; Ministry of Science and Technology of Korea: Research Funding. Fleury: Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Consultancy, 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; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Laribi: Abbvie: Honoraria, Research Funding; AstraZeneca: Honoraria; BeiGene: Honoraria; Takeda: Honoraria; Jansen: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria, Research Funding; Amgen: Honoraria. Portell: Merck, Prelude, BeiGene, AstraZeneca, SeaGen/Pfizer, Infinity, Genentech/Roche, Kite: Research Funding; Merck, BeiGene, Jansen, AstraZeneca, AbbVie: Consultancy. Boutin: CISSS Montérégie-Centre: Current Employment; BMS, Merck, Roche, Amgen, Beigene, Abbvie, Incyte: Consultancy; BMS, Merck, Roche, Amgen, Beigene, Abbvie, Incyte, Pfizer, Amgen, Taiho, Ipsen, AAA: Honoraria; Roche, Pfizer, Incyte: Research Funding. Lam: AbbVie, Amgen, AstraZeneca, Beigene, Bristol-Myers Squibb, Forus, Gilead, Hoffman-Roche, Incyte, Janssen, Novartis, Pfizer, Johnson & Johnson, Sanofi: Honoraria. Joergensen: Sobi: Consultancy; Novo Nordisk: Current holder of stock options in a privately-held company; Abbvie: Consultancy; Roche: Consultancy; Caribou: Consultancy; Incyte: Consultancy; Kite/Gilead: Consultancy. Ghesquieres: Gilead, Roche, BMS, Abbvie, Takeda: Honoraria; Roche, BMS, Takeda: Consultancy. Nowakowski: Blueprint Medicines Corporation: Consultancy; Ryvu Therapeutics: Consultancy; Incyte Corporation: Consultancy; F. Hoffmann-La Roche Limited: Consultancy; MorphoSys AG: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Fate Therapeutics: Consultancy; Genentech: Consultancy; Selvita Inc: Consultancy; Karyopharm Therapeutics: Consultancy; AbbVie Inc.: Consultancy; Debiopharm: Consultancy; Zai Laboratory: Consultancy; MEI Pharma: Consultancy; Curis: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; Constellation Pharmaceuticals: Consultancy; Segen: Consultancy; Bantam Pharmaceutical, LLC: Consultancy; TG Therapeutics Inc: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Kymera Therapeutics: Consultancy. Yasenchak: Pfizer: Consultancy; Beigene: Speakers Bureau. Patterson: Scorpion Therapeutics, Inc.: Ended employment in the past 24 months; Pfizer: Current Employment. Ho: Pfizer Inc.: Current Employment. Rustia: Pfizer Inc, Gilead Inc: Current equity holder in publicly-traded company; Seagen Inc: Divested equity in a private or publicly-traded company in the past 24 months; Gilead Inc: Ended employment in the past 24 months; Pfizer Inc (former Seagen Inc employee acquired by Pfizer): Current Employment. Fanale: Seagen: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; Pfizer: Current Employment, Current holder of stock options in a privately-held company. Fenton: Pfizer: Current Employment; Seagen: Ended employment in the past 24 months. Ribrag: Employment: Ended employment in the past 24 months; AstraZeneca: Honoraria; AstraZeneca, Lilly: Membership on an entity's Board of Directors or advisory committees; Astex, GSK: Research Funding; Abbvie, Ipsen: Speakers Bureau; Belgene: Speakers Bureau; Pegascy: Current Employment.

OffLabel Disclosure: Brentuximab vedotin is not approved for use in DLBCL. The ECHELON-3 clinical trial is exploring brentuximab vedotin in combination with lenalidomide and rituximab

*signifies non-member of ASH