Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Adult, Lymphomas, Non-Hodgkin lymphoma, Bispecific Antibody Therapy, Clinical Research, B Cell lymphoma, Diseases, Aggressive lymphoma, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Study Population, Human
Methods: Adult pts with R/R CD20+ LBCL (including diffuse LBCL [DLBCL], high‑grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and FL grade 3B) and ≥2 prior lines of systemic antilymphoma therapy were treated with epcoritamab SC (2 step-up doses followed by 48-mg full doses) in 28‑d cycles. Pts were treated QW, cycles 1–3; Q2W, cycles 4–9; and Q4W, cycles ≥10, until progressive disease or unacceptable toxicity. Corticosteroid prophylaxis was used during cycle 1. The primary endpoint was ORR per Lugano criteria. Minimal residual disease (MRD) was evaluated using the clonoSEQ® (Adaptive Biotechnologies) ctDNA assay.
Results: A total of 96 CAR T–naive pts with R/R LBCL were treated with epcoritamab. Median age was 69 y (range, 31–83 [median age in the total R/R LBCL population (N=157), 64 y]) and 60% were male. The median number of prior lines of therapy was 3 (range, 2–11), and 50 pts (52%) had ≥3 prior lines. At data cutoff (May 3, 2024), 13 pts (14%) remained on epcoritamab; the most common reasons for treatment discontinuation were progressive disease in 52 pts (54%) and adverse events in 22 pts (23%). The ORR and CR rate per investigators were 61% and 45% (median study follow-up, 37.3 mo [range, 0.3+ to 45.5]). Median duration of response was 18.4 mo (95% CI, 9.7–30.4). Median duration of CR was 28.6 mo (95% CI, 15.8 to not reached [NR]) and an estimated 46% remained in CR at 36 mo. Median progression-free survival (PFS) was 4.3 mo (95% CI, 3.4–10.9) overall and 33.3 mo (95% CI, 19.4–NR) among complete responders. Median overall survival (OS) was 15.4 mo (95% CI, 11.0–27.8) overall and NR (95% CI, 27.8–NR) among complete responders. At 36 mo, an estimated 40% of pts overall and 83% of complete responders had not initiated their next antilymphoma therapy. Among 35 pts who received subsequent antilymphoma therapy, 10/35 (29%) received CAR T; 6 of these 10 pts remain alive at data cutoff. Of 74 MRD-evaluable pts, 33 (45%) were MRD negative. In a cycle 3 day 1 landmark analysis, estimated 36-mo rates of PFS/OS were 42%/52% among MRD-negative pts and 16%/31% among MRD-positive pts. The most common treatment‑emergent AEs (TEAEs) were cytokine release syndrome (CRS; 60%), diarrhea (24%), pyrexia (23%), fatigue (22%), neutropenia (22%), and injection-site reaction (21%). Fatal TEAEs were reported in 18 pts; 9 of 18 events were related to COVID‑19. TEAEs led to treatment discontinuation in 22 pts (23%) and were most commonly COVID-19 pneumonia (8%), COVID-19 (3%), and pneumonia (2%). CRS events were mostly grade 1 (33%) or grade 2 (23%); 4% of pts had grade 3 CRS. CRS was most common following the first full (cycle 1 day 15) dose (median time to onset, 20 h). CRS resolved in all but 2 pts and led to treatment discontinuation in 1 pt. ICANS occurred in 7 pts (7%; grade 1, 6%; grade 5, 1%). Clinical tumor lysis syndrome occurred in 2 pts (2%; each grade 3). Immunoglobulin G levels decreased by a median of ~20% after the start of epcoritamab treatment (baseline median: 653.0 mg/dL) and remained stable over time.
Conclusions: With over 3 years of follow-up, single-agent epcoritamab demonstrated deep and durable responses and manageable side effects in CAR T–naive pts with R/R LBCL, as demonstrated by this subgroup analysis. Results were consistent with those seen in the overall EPCORE NHL-1 LBCL population, considering differences in baseline characteristics, and show that epcoritamab can be administered safely and effectively before or after CAR T for the treatment of R/R LBCL.
Disclosures: Karimi: AstraZeneca: Research Funding; Lilly/Loxo: Research Funding; Merck: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria; Xencor: Research Funding; Roche/Genentech: Other: Travel Expenses, Research Funding. Clausen: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria, Other: Travel Expenses; Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses; Incyte: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: Travel Expenses; Pfizer: Other: Travel Expenses. Lewis: Janssen, Lilly, Roche, BeiGene, Kite, Astrazeneca: Consultancy, Honoraria. Jurczak: Janssen Cilag: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Merck: Research Funding; Roche: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; MSD: Research Funding; Lilly: Consultancy, Research Funding; Regeneron: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding. Kim: Takeda: Consultancy, Honoraria; Regeneron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Samsung Bioepis: Consultancy; Amgen: Consultancy, Honoraria; Daiichi Sankyo, HK inno.N, F. Hoffmann-La Roche Ltd/Genentech, Yuhan: Consultancy; Yuhan: Consultancy; BeiGene: Membership on an entity's Board of Directors or advisory committees; Roche/Genetech: Consultancy; IMBDx. Inc.: Consultancy, Honoraria; Novartis: Consultancy; Janssen: Consultancy, Honoraria; Boryung: Consultancy; AstraZeneca/MedImmune: Consultancy. Lugtenburg: Y-mAbs Therapeutics: Other: Consultancy Honoraria; BMS, Roche, Takeda, Genmab, AbbVie, Incyte, Regeneron, Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda, Servier: Research Funding. Conte: AbbVie: Current Employment. Soong: Genmab: Current Employment, Current equity holder in publicly-traded company. D'Angelo Månsson: Genmab: Current Employment. Li: Genmab: Current Employment. Eskelund: Genmab: Current Employment. Hutchings: BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Incyte: Research Funding; Janssen/J&J: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding.
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