Type: Oral
Session: 626. Aggressive Lymphomas: Clinical and Epidemiological: CARs, Bispecifics, and ADCs: Progress and Challenges in Aggressive B Cell Lymphoma
Hematology Disease Topics & Pathways:
Research, Adult, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, B Cell lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Real-world evidence, Treatment Considerations, Biological therapies, Registries, Lymphoid Malignancies, Study Population, Human
Methods: This observational study included pts in the United States who received commercial liso-cel as 2L therapy between 06/2022 and 05/2024 and had ≥ 1 postinfusion safety and response assessment reported in the CIBMTR Registry. Outcomes evaluated included ORR, CR rate, duration of response (DOR), PFS, OS, AEs of special interest (AESI), and nonrelapse mortality (NRM; defined as death before disease progression/relapse). Univariable Logistic Regression was used to assess association between increasing age and early effectiveness outcomes.
Results: At data cutoff (05/07/2024), in 128 eligible pts, median age was 73 y (range, 24–85; ≥ 70 y, 55%; ≥ 75 y, 43%) and 57% were male. Most pts (80%) had DLBCL (germinal center B cell type, 50 pts; activated B-cell type, 39 pts; not otherwise specified, 13 pts), 14% had high-grade B-cell lymphoma, and 6% had other histologies. At the time of infusion, 91% of pts had active disease, 62% had primary refractory disease, and 54.5% (60/110) had extranodal involvement, including 4.5% (5/110) with CNS involvement. In 107 pts with ECOG PS data, 5% had ECOG 2 and none had ECOG 3 or 4. At least 1 comorbidity was reported in 62/105 (59%) pts with available data, with cardiac (24%), pulmonary (13%), and obesity (14%) being the most common (> 10%); 45% (55/123) of pts had elevated LDH at infusion, and ≥ 65% (84 pts) would have been TRANSFORM ineligible mainly due to age and/or comorbidities. Of 121 pts with available data on prior therapies, 91% had received R-CHOP (single regimen, 59%; with other chemotherapy regimens, 41%), and 18% and 21% received intrathecal and radiation therapies, respectively. Most pts (73% [86/118]) received bridging therapy.
At a median (range) follow-up of 6.2 mo (0.3–13.8), ORR and CR rate (95% CI) in the overall cohort were 84% (77–90) and 68% (59–76), respectively. TRANSFORM-ineligible pts (n = 83) had ORR of 82% (72–90) and CR rate of 65% (54–75), while those who might have been eligible (n = 44) had ORR of 89% (75–96) and CR rate of 73% (57–85). Median DOR, PFS, and OS were not reached.
Early-response analysis of the population stratified by age showed that pts < 70 y (n = 57) had ORR and CR rate (95% CI) of 88% (76–95) and 79% (66–89), respectively; pts ≥ 70 y (n = 71) had ORR and CR rate (95% CI) of 81% (70–90) and 59% (46–70). Further, younger age was associated with significantly higher CR rates (P < 0.05). Additional subgroup analyses, such as stratification by PILOT criteria, and multivariable analyses will be included in the presentation.
Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were reported in 45% (grade 1, 37 pts; grade 2, 17 pts; 1 pt each with grade 3, 4, and 5) and 20% (grade 3, 7 pts; none with grades 4 or 5) of pts, respectively. Other reported AESIs were prolonged cytopenia (grade ≥ 4 at Day 30; 9% [11/124]), clinically significant infections (28%), second primary malignancies (2%; none of hematologic origin), and 6 cases of grade 3/4 organ toxicity; no tumor lysis syndrome was reported. The 6-mo cumulative incidence of NRM was 2.7% (95% CI, 0.7–7.1) and that of relapse/progression or death due to primary disease was 40.4% (95% CI, 31.0–49.7). There were 3 deaths ≤ 30 d of infusion; 2 were due to progression of primary disease (including 1 pt with grade 5 CRS noted as a contributing cause) and 1 due to cardiac failure.
Conclusions: Liso-cel continued to demonstrate consistently deep responses in this broad, albeit older, RW pt cohort with 2L R/R LBCL, with early responses being stronger in pts aged < 70 y and those who might have been eligible for TRANSFORM. The safety profile remained predictable; most pts did not experience, or had low-grade CRS, ICANS, prolonged cytopenia, or infections. While longer follow-up in a larger cohort is needed, these results provide additional compelling evidence supporting the use of liso-cel as 2L SOC treatment for pts, young and old alike, with R/R LBCL.
Disclosures: Thiruvengadam: ADC-Therapeutics: Research Funding; Abbvie: Consultancy; Genmab: Consultancy, Research Funding; Genentech: Research Funding; Ipsen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Hunter: Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Notable Labs: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; In8 Bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Patel: Morphosys: Consultancy; Merck: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; Loxo Oncology: Consultancy, Research Funding; Kite: Consultancy, Research Funding, Speakers Bureau; Genentech/Roche: Consultancy, Research Funding; Fate Therapeutics: Research Funding; Epizyme: Consultancy, Research Funding; Curis, Inc: Research Funding; CRISPR Therapeutics: Research Funding; Caribou Biosciences: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding, Speakers Bureau; BeiGene: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Research Funding; ADC Therapeutics: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Nurix: Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; Sunesis Pharmaceuticals: Consultancy, Research Funding; TG Therapeutics: Consultancy, Speakers Bureau; Trillium Therapeutics/Pfizer: Consultancy, Research Funding; Xencor: Consultancy, Research Funding. Reagan: Caribou Biosciences: Consultancy; Seagen: Research Funding; Genentech: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria. Bernasconi: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Krimmel: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Liu: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Roy: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Ahmed: Bristol Myers Squibb: Research Funding; Merck: Research Funding; Xencor: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Nektar: Research Funding; Myeloid Therapeutics: Consultancy; Janssen: Research Funding; ADC Therapeutics: Consultancy. Crombie: Abbvie: Research Funding; Bayer: Research Funding; Genentech/Roche: Research Funding; Merck: Research Funding; Genentech: Consultancy; Genmab/Abbvie: Consultancy; Seagen: Consultancy; Regeneron Pharmaceuticals, Inc.: Consultancy; ADCT: Consultancy. Dahiya: Bristol Myers Squibb: Consultancy; Kite-Pharma-Gilead: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy. Hamadani: AstraZeneca: Speakers Bureau; Byondis: Consultancy; BeiGene: Speakers Bureau; Autolus: Consultancy; CRISPR: Speakers Bureau; Caribou: Consultancy; AbbVie: Consultancy; Takeda: Research Funding; Sanofi Genzyme: Speakers Bureau; Forte Biosciences: Consultancy; DMC, Inc: Speakers Bureau; Genentech: Speakers Bureau; Myeloid Therapeutics: Speakers Bureau; CRISPR: Consultancy; Allovir: Consultancy; Genmab: Consultancy; BMS: Consultancy; Omeros: Consultancy; Astellas Pharma: Research Funding; Kite Pharma: Consultancy, Speakers Bureau; Spectrum Pharmaceuticals: Research Funding; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau. Lee: ScientiaCME: Consultancy; Aptitude Health: Consultancy; Sanofi: Consultancy, Honoraria, Speakers Bureau; SEI: Consultancy; Incyte: Consultancy, Honoraria, Research Funding. Pasquini: Kite, a Gilead Company: Honoraria, Research Funding; Janssen: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Shadman: Mustang Bio, Genentech, AbbVie/Pharmacyclics, Beigene, AstraZeneca, Genmab, Morphosys/Incyte, Vincerx, BMS, TG Therapeutics: Research Funding; Atara Biotherapeutic: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Adaptimmune: Consultancy; Epizyme: Consultancy; Adaptive Biotechnologies: Consultancy; Lilly: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; BMS: Other: Current employment of spouse; AbbVie/Pharmacyclics, Genentech, AstraZeneca, Genmab, Janssen, Beigene, Bristol Myers Squibb, Morphosys/Incyte, Kite Pharma, Eli Lilly, Fate Therapeutics, Nurix, Merck, ADC Therapeutics, MEI Pharma, MustangBio, Regeneron: Consultancy; Koi Biotherapeutics: Current holder of stock options in a privately-held company; Fate Therapeutics: Consultancy; Genentech: Consultancy, Research Funding; Innate Pharma: Consultancy; Kite, a Gilead Company: Consultancy; MEI Pharma: Consultancy; Merck: Consultancy; MorphoSys/Incyte: Consultancy, Research Funding; Mustang Bio: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Regeneron: Consultancy; Sound Biologics: Consultancy; TG Therapeutics: Consultancy, Research Funding; Celgene: Research Funding; Genmab: Research Funding; Gilead Sciences: Research Funding; Sunesis: Research Funding. Herrera: Caribou Biosciences: Consultancy; Allogene Therapeutics: Consultancy; Pfizer: Consultancy; AbbVie: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Adicet Bio: Consultancy; Takeda: Consultancy; Tubulis: Consultancy; Merck: Consultancy, Research Funding; Roche/Genentech: Consultancy, Research Funding; Regeneron: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Genmab: Consultancy; Seattle Genetics: Consultancy, Research Funding; Gilead Sciences: Research Funding; KiTE Pharma: Research Funding; Karyopharm: Consultancy. Frigault: Novartis: Consultancy; SOBI: Research Funding; Iovance: Consultancy; Cytoagents: Consultancy; JNJ/Legend: Consultancy; Bristol Meyers Squibb: Consultancy; Kite, a Gilead Company: Consultancy.