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470 Real-World (RW) Outcomes of Lisocabtagene Maraleucel (liso-cel) As Second-Line (2L) Therapy in Patients (pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): First Results from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

Program: Oral and Poster Abstracts
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
Sunday, December 8, 2024: 9:45 AM

Maria Silvina Odstrcil Bobillo, MD1*, Swetha Kambhampati, MD2, Dasom Lee3, Bradley D. Hunter, MD, MPH4, Ogechukwu Egini, MD, MS5*, Krish Patel, MD6, Patrick M. Reagan, MD7, David Bernasconi, MSc8*, Soyoung Kim, PhD9*, Charimar Santiago Parrilla, MPH10*, Tracy Krimmel, MSN, DNP11*, Fei Fei Liu, GDCE, MBA11*, Debasmita Roy, PhD11*, Sairah Ahmed, MD12, Jennifer L. Crombie, MD13, Saurabh Dahiya, MD, FACP14,15*, Mehdi Hamadani, MD16, Catherine J. Lee, MD, MSc17, Marcelo C. Pasquini, MD, MS9, Mazyar Shadman, MD, MPH18*, Alex F. Herrera, MD19 and Matthew Frigault, MD, MS20

1University of Utah School of Medicine, Salt Lake City, UT
2City of Hope National Medical Center, Duarte, CA
3Stanford School of Medicine, Stanford, CA
4Intermountain LDS Hospital, Salt Lake City, UT
5Rutgers Cancer Institute, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ
6Swedish Cancer Institute, Center for Blood Disorders and Cellular Therapy, Seattle, WA
7University of Rochester Medical Center, Rochester, NY
8Bristol Myers Squibb, Boudry, Switzerland
9Center for International Blood & Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI
10Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI
11Bristol Myers Squibb, Princeton, NJ
12MD Anderson Cancer Center, Houston, TX
13Dana-Farber Cancer Institute, Boston, MA
14Stanford University School of Medicine, Stanford, CA
15University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD
16BMT & Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, WI
17Fred Hutchinson Cancer Center, University of Washington, Seattle, WA
18Fred Hutch Cancer Center, University of Washington, Seattle, WA
19Duarte Cancer Center, City of Hope Medical Center, Duarte, CA
20Massachusetts General Hospital, Boston, MA

Background: The increasing use of CAR T cell therapies in the 2L setting underscores the need to evaluate outcomes in the context of standard of care (SOC), including in pts ineligible for clinical trials. Liso-cel demonstrated significant efficacy in the TRANSFORM (NCT03575351) and PILOT (NCT03483103) studies in pts with R/R LBCL in the 2L setting, regardless of pts’ transplantation eligibility. Here, we report on the effectiveness and safety of liso-cel as SOC based on CIBMTR data collected as part of a postmarketing study for 2L R/R LBCL.

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: Kambhampati: 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.

*signifies non-member of ASH