Type: Oral
Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: 'In with the Old, In with the New': Outcomes of Conventional and Novel Therapeutic Paradigms in Aggressive Lymphoid Malignancies
Hematology Disease Topics & Pathways:
Research, Adult, Lymphomas, Bispecific Antibody Therapy, Clinical Research, Health outcomes research, B Cell lymphoma, Diseases, Real-world evidence, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Study Population, Human
Methods: We performed a retrospective study including 19 US centers evaluating pts with r/r LBCLs receiving commercially available Epco or Glofit between 2023 and 2024. Baseline characteristics and outcomes were extracted from medical records. Efficacy outcomes included overall response rate (ORR), complete and partial response (CR, PR) rates, progression-free survival (PFS) and overall survival (OS), analyzed using the Kaplan Meier method. Key safety outcomes included cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
Results: As of May 31, 2024, a total of 209 pts with r/r LBCLs were treated with Epco (n=139) or Glofit (n=70). Median age at BsAb start was 67 years (interquartile range [IQR] 58-76). Most were male (62.2%), and the most common histology was diffuse large B-cell lymphoma (n=155 [74.2%]). Of pts with molecular testing (n=168), 34 (20.2%) had double/triple hit lymphoma. Most (78.9%) had Ann Arbor stage III-IV disease and 91% had an ECOG performance status of ≤1. Median number of lines of treatment before BsAb was 3 (range 1-12). Of pts with known response assessment following front-line therapy, 54 (32.1%) had primary refractory disease, defined as failure to achieve PR or CR to front-line therapy. Most pts (n=126 [60.3%]) received prior chimeric antigen receptor (CAR) T-cell therapy and 21 (10.0%) received prior autologous hematopoietic progenitor cell transplant. CD20 expression was assessed in 106 biopsies (50.7%) prior to BsAb and was positive in 90 (84.9%). A total of 172 pts were response-evaluable. The best ORR was 50.6%, with CR in 41 (23.8%), PR in 46 (26.7%), stable disease in 10 (5.8%), and progressive disease in 75 (43.6%). The ORR and CR rates were 49% and 23% for Epco, and 53% and 25% for Glofit, respectively. With a median follow-up of 5 months, the median PFS was 2.7 months (95% CI 2.0, 3.9) and median OS was 7.2 months (95% CI 6.1, not reached [NR]). The estimated PFS and OS at six months were 35% (95% CI 29%-43%) and 59% (95% CI 52%-67%), respectively. For pts who relapsed after CAR T-cell therapy, the median PFS and OS were 2.5 (95% CI 1.8, 4.7) and 7.8 (95% CI 6.2, NR) months, respectively. Pts without detectable CD20 expression via immunohistochemistry or flow cytometry prior to BsAb therapy had significantly inferior outcomes (PFS 1.1 vs 3.4 months, P < 0.001 and OS 1.3 vs 13 months, P < 0.001) compared to pts with detectable CD20. CRS of any grade occurred in 82 pts (39.2%), corresponding to 51.1% and 28.6% of pts treated with Epco and Glofit, respectively. Grade ≥3 CRS occurred in 9 (4.3%), all of whom received Epco. CRS was treated with tocilizumab in 43 pts (53.1%). ICANS occurred in 24 (11.5%) pts; any grade ICANS occurred in 13.7% and 7.1% of pts treated with Epco and Glofit, respectively. Grade ≥3 ICANS occurred in 6 pts (2.9%), 5 of which received Epco (3.6%). Of those experiencing ICANS, 66.0% were treated with corticosteroids. Two pts had deaths attributed to ICANS and one to CRS. A total of 122 (58.4%) pts discontinued therapy after a median of 3 cycles (range 0-48), 91 (74.6%) due to disease progression and 31 (25.4%) due to adverse events (15 due to infection, 3 due to ICANS, 2 due to CRS, and 11 for other reasons).
Conclusions: In this heavily pretreated group with adverse disease features and high rate of CAR T exposure, the response rates, PFS, and OS following BsAb therapy were lower compared to pivotal trials. Poor outcomes were observed for those without detectable CD20. Rates of ICANS and grade ≥3 CRS were higher than reported in pivotal trials, as was the rate of discontinuation of therapy due to adverse events. Future efforts to improve outcomes may include intensified dose escalation protocols to more rapidly achieve disease control, combination therapies, and characterization of clinicopathologic factors that predict response to BsAb to identify subgroups of pts who can derive maximal benefit from these agents.
Disclosures: Landsburg: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GenMab: Honoraria; Calithera: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Wang: InnoCare, AbbVie: Consultancy; Kite: Honoraria; Eli Lilly, LOXO Oncology, TG Therapeutics, Incyte, InnoCare, Kite, Jansen, BeiGene, AstraZeneca, Genmab, AbbVie: Other: Advisory Board; Incyte, InnoCare, LOXO Oncology, Eli Lilly, MorphoSys, Novartis, Genentech, Genmab, AbbVie, BeiGene, Merck: Research Funding. Major: Roche/Genentech: Consultancy; Incyte: Research Funding. Ghosh: Bristol Myers Squibb: Consultancy, Research Funding, Speakers Bureau; ADC Therapeutics: Consultancy; BeiGene: Consultancy; Abbvie: Consultancy, Speakers Bureau; Adaptive Biotech: Consultancy; Genmab: Consultancy; Gilead/Kite: Consultancy, Speakers Bureau; Incyte: Consultancy; Janssen: Consultancy, Speakers Bureau; Lava Therapeutics: Consultancy. Grover: Ono Pharma: Honoraria; Genentech: Honoraria; Cabaletta: Research Funding; Janssen: Honoraria; Kite: Honoraria; Sangamo: Current holder of stock options in a privately-held company; Caribou: Honoraria; BMS: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Regeneron: Honoraria, Research Funding; Novartis: Honoraria; Seagen: Honoraria; Poseida: Research Funding. Khan: ABBVIE INC.: Consultancy, Speakers Bureau; Genentech USA, Inc.: Consultancy, Speakers Bureau; Pharmacyclics LLC, An AbbVie Company: Speakers Bureau; Genmab U.S., Inc.: Consultancy. Narkhede: Beigene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genmab: Consultancy, Honoraria, Research Funding; EUSA/Recordati Disease: Research Funding; Lilly Oncology: Speakers Bureau; Natera: Research Funding; Genentech-Roche: Speakers Bureau; Adaptive Biotechnologies: Speakers Bureau; Abbvie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Cullinan Oncology: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding. Smith: Bayer: Research Funding; Beigene: Consultancy, Research Funding; Coherus Biosciences (spouse): Consultancy; AstraZeneca: Consultancy, Research Funding; ADC therapeutics: Consultancy, Research Funding; abbvie: Consultancy; Enterome: Research Funding; BMS (spouse): Research Funding; De Novo Biopharma: Research Funding; Genentech: Consultancy, Research Funding; Epizyme: Consultancy; Incyte: Consultancy, Research Funding; Karyopharm: Consultancy; KITE pharma: Consultancy; Kymera Therapeutics: Research Funding; Lumanity: Consultancy; Millenium/Takeda: Consultancy; Ignyta (spouse): Research Funding; Merck Sharp and Dohme Corp: Research Funding. Kline: Curio Science: Honoraria; Merck: Research Funding; Gilead Sciences: Consultancy; BMS: Consultancy; BeiGene: Consultancy; Abbvie: Consultancy; Genmab: Consultancy; Seagen: Consultancy; Targeted Oncology: Honoraria. Hu: ImmPACT Bio, Caribou Biosciences, Genentech, CRISPR Therapeutics, Morphosys AG, Repare Therapeutics, Artiva Biosciences, Newave, Astrazeneca: Research Funding; Eli Lilly, Genmab, ADC Therapeutics, ImmPACT Bio, SeaGen, Regeneron, Caribou Biosciences, Abbvie, Kite Pharma, Bristol-Myers Squibb: Consultancy, Honoraria. Pophali: Marker Therapeutics: Research Funding; Fate Therapeutics: Research Funding; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Karimi: ADC Therapeutics: Consultancy, Honoraria; AstraZeneca: Research Funding; Xencor: Research Funding; Lilly/Loxo: Research Funding; Merck: Research Funding; Roche/Genentech: Other: Travel Expenses, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Hernandez-Ilizaliturri: Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Dava Oncology: Consultancy; Epizyme: Consultancy; Gilead: Consultancy; Ipsen: Honoraria; Morphosys: Consultancy; Kite Pharmaceuticals: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Honoraria; Novartis: Consultancy; Pharmacyclics: Consultancy; BioGene: Consultancy; AbbVie: Consultancy; ADC Therapeutics: Consultancy; AbbVie: Consultancy, Research Funding; Cellectar Biosciences: Consultancy, Research Funding. Munoz: Kyowa: Consultancy; Alexion: Consultancy; Pfizer: Consultancy; Fosunkite: Consultancy; Karyopharm: Consultancy; Aurobindo: Consultancy; Verastem: Consultancy, Research Funding; Genmab: Consultancy; Genzyme: Consultancy; Genentech/Roche: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Epizyme: Consultancy; Novartis: Consultancy, Research Funding; Morphosys/Incyte: Consultancy, Research Funding; MEI: Consultancy; TG Therapeutics: Consultancy; AstraZeneca: Consultancy; Eli Lilly: Consultancy; Bayer: Consultancy, Research Funding; Merck: Research Funding; Portola: Research Funding; Curio: Honoraria; OncView: Honoraria; Physicians' Education Resource: Honoraria; Targeted Oncology: Honoraria; Alexion: Consultancy; BeiGene: Consultancy; Pharmacyclics/Abbvie, Bayer, Gilead/Kite, Beigene, Pfizer, Janssen, Celgene/Bristol Myers Squibb, Kyowa, Alexion, Fosunkite, Seattle Genetics, Karyopharm, Aurobindo, Verastem, Genmab, Genzyme, Genentech/Roche, ADC Therapeutics, Epizyme, Beigene, Novartis,: Consultancy; Celgene/Bristol Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Bayer, Gilead/Kite, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium, Novartis, Beigene.: Research Funding; Targeted Oncology, OncView, Curio, Genzyme, and Physicians' Education Resource.: Honoraria; Gilead/Kite: Consultancy, Research Funding; Pharmacyclics/Abbvie: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Research Funding. Alhaj Moustafa: AbbVie: Consultancy. Caimi: Recordati: Honoraria, Research Funding; Abcon: Research Funding; Abbvie: Honoraria, Research Funding; BMS: Other: Avisory Board, Research Funding; Novartis: Other: Advisory Board; Genentech: Other: Advisory Board, Research Funding; Sobi: Honoraria; Synthekine: Other: Advisory Board, Research Funding; Luminary Therapeutics: Other: Scientific Advisory Board, Research Funding; Genmab: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Profound Bio: Research Funding; Arvinas: Honoraria, Research Funding. Hill: Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Consultancy, Honoraria, Research Funding.