Abstract
5 min readIntroduction: TRANSCEND FL, a phase 2, single-arm study (NCT04245839), demonstrated the efficacy of the CD19-directed CAR T cell product liso-cel in patients (pts) with 3L+ R/R FL, with an ORR of 97% and CR rate of 94% (Morschhauser F, et al. Nat Med 2024). The current study compared efficacy outcomes of liso-cel from TRANSCEND FL with standard of care (SOC) in pts with 3L+ R/R FL from routine practice. Methods: An ECA cohort applying key TRANSCEND FL eligibility criteria was constructed using historical clinical trials (AUGMENT [NCT01938001] and MAGNIFY [NCT01996865]) and observational real-world (RW) data from the United States (COTA database) and 6 European countries (clinicians/hospital sites). AUGMENT and MAGNIFY evaluated lenalidomide plus rituximab (R2) in pts with second-line or later R/R FL. R2 is used in the 3L+ RW setting, making pts with 3L+ FL from these studies who met TRANSCEND FL eligibility criteria appropriate for the ECA cohort. Propensity score methodologies balanced the ECA to the TRANSCEND FL cohorts by prespecified baseline characteristics and prognostic factors. Balancing was performed using trimmed, stabilized inverse probability of treatment weighting (IPTW). The primary analysis cohort from TRANSCEND FL was the liso-cel–treated efficacy analysis cohort (n = 103). A sensitivity analysis was conducted using the leukapheresed cohort (n = 114). Subgroup analyses included restricting the ECA cohort to RW pts. The primary endpoint was ORR. Secondary endpoints included CR rate, PFS, time to next treatment (TTNT), OS, and duration of response (DOR). Response data were by investigator assessment. Generalized linear models were used to estimate relative risk for ORR and CR rate, and Cox proportional hazards models were used to estimate HR for PFS, TTNT, OS, and DOR. Results: A total of 531 pts were included in the ECA cohort (n = 231 from AUGMENT and MAGNIFY and n = 300 RW pts). The most common treatments in the ECA cohort were R2 (n = 272 [51%]), rituximab (n = 54 [10%]), bendamustine + rituximab (BR) or bendamustine + obinutuzumab (BO) (n = 62 [12%]), idelalisib (n = 19 [4%]), and zanubrutinib + obinutuzumab (ZO) (n = 19 [4%]). In the RW cohort, the most common treatments were R2 (n = 91 [30%]), BR or BO (n = 62 [21%]), idelalisib (n = 19 [6%]), and ZO (n = 19 [6%]). After balancing using trimmed, stabilized IPTW, statistically significantly better outcomes were observed with liso-cel for all measured endpoints (ORR, CR rate, PFS, TTNT, OS, and DOR) compared with SOC treatments in the ECA cohort (Table). Results of the sensitivity and subgroup analyses were consistent with the primary analysis. Conclusion: Liso-cel demonstrated statistically significantly better efficacy than SOC therapies for pts with 3L+ R/R FL, representing an important treatment option to improve pt outcomes in this setting. Research funding declaration: This study was funded by Bristol Myers Squibb. All authors contributed to and approved the abstract; writing and editorial assistance were provided by Robert Schupp, PharmD, CMPP, of The Lockwood Group (Stamford, CT, USA), funded by Bristol Myers Squibb. Keywords: non-Hodgkin; Cellular therapies; indolent non-Hodgkin lymphoma Potential sources of conflict of interest: L. J. Nastoupil Consultant or advisory role: Research support and honorarium for advisory committee participation: BMS Stock ownership: Research support Honorarium: Daiichi Sankyo, Genentech, Gilead/Kite, Janssen, Incyte, Novartis, Takeda; Honorarium: AstraZeneca, Regeneron, Merck A. M. García-Sancho Employment or leadership position: GELTAMO Foundation Consultant or advisory role: Consulting fees: Abbvie, AstraZeneca, BMS, Genmab, Gilead/Kite, GSK, Ideogen, Incyte, Janssen, Lilly, Miltenyi, Regeneron, Roche, Sobi; Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca, BMS, Regeneron Honoraria: Abbvie, AstraZeneca, BeiGene, BMS, Gilead/Kite, Ideogen, Incyte, Janssen, Kyowa Kirin, Lilly, Roche, Sobi, Takeda Educational grants: Roche, Abbvie, Gilead/Kite, BMS, Lilly K. Izutsu Consultant or advisory role: MSD, AstraZeneca, Abbvie, Bristol Myers Squibb, Novartis, Yakult, Kyowa Kirin, Chugai, Beigene, Genmab, Otsuka, Ono Pharma, Mitsubishi Tanabe Pharmaceutical, Eisai, Symbio, Taked, Zenyakua, Carna Biosciences, Nihon Shinyaku Honoraria: AstraZeneca, Abbvie, Bristol Myers Squibb, Novartis, Pfizer, Janssen, Kyowa Kirin, Daiichi Sankyo, Chugai, Genmab, Gilead, Ono Pharmac, Nihon Kayakueutical, Symbio, Takeda, Lilly, Astellas, Meiji Seika Pharma Other remuneration: Research funding: MSD, AstraZeneca, Abbvie, Incyte, Bristol Myers Squibb, Novartis, Bayer, Pfizer, Janssen, Yakult, Kyowa Kirin, Daiichi Sankyo, Chugai, Beigene, Genmab, LOXO Oncology, Otsuka, Regeneron, Gilead G. Cartron Consultant or advisory role: BMS, Roche, Onwards Therapeutics, MabQi Honoraria: Jansen, Takeda, Abbvie, Jansen, NOvartis Educational grants: Roche, Jansen A. P. Skarbnik Consultant or advisory role: AstraZeneca, Abbvie, Alexion, Bristol-Myers-Squibb, Celgene, Epizyme, Genentech, GenMab, Jazz Pharmaceuticals, Kite Pharma, Lilly, Janssen, MorphoSys, Novartis, SeaGen, Beigene Honoraria: AstraZeneca, Abbvie, Bristol Myers Squibb, Genentech, GenMab, Jazz Pharmaceuticals, ADC Therapeutics, Kite Pharma, Lilly, Janssen, Seagen J. L. Reguera Ortega Consultant or advisory role: Johnson and Johnson, Kite Educational grants: Johnson and Johnson Other remuneration: Speakers' Bureau: Kite, BMS, Amgen, Johnson and Johnson H. Goto Honoraria: Abbvie, BMS, Novartis, Gilead, Chugai, Kyowa Kirin, Takeda, Meiji, MSD Other remuneration: Research Funding: Sanofi, BMS, Gilead, Kyowa Kirin, Symbio P. Borchmann Consultant or advisory role: Takeda Oncology BMS Roche Miltenyi Biotec Gilead MSD (personal) Honoraria: Takeda Oncology BMS Roche MSD Miltenyi Biotec Gilead Abbvie Incyte Beigene AstraZeneca (personal) Educational grants: Takeda Oncology Roche Miltenyi Biotec Gilead Incyte BMS (personal) Other remuneration: Grants or Contracts: Takeda Oncology, MSD, Incyte, Miltenyi Biotec (institution) T. Farazi Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb M. Bar Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb M. del Rosario Olivera Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb J. Kumar Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb M. De Benedetti Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb F. Gu Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb D. Stein Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb J. Han Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb M. L. Palomba Consultant or advisory role: Synthekine, Kite, Novartis, Bristol Myers Squibb
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