Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies
Methods: Individual patient data for liso-cel from TRANSCEND FL (N = 101 for treated efficacy set, N = 107 for treated set; data cutoff: 27 Jan 2023; median follow-up of 19.3 months) and aggregate data for axi-cel from ZUMA-5 (NCT03105336, N = 86 for updated analysis set, N = 124 for treated set; data cutoff: 14 Sep 2020; median follow-up of 24.4 months) and for tisa‑cel from ELARA (NCT03568461, N = 94 for efficacy set, N = 97 for treated set; data cutoff: 29 Mar 2021; median follow-up of 16.85 months) were used for the MAICs. Efficacy outcomes included response (ORR and CR rate) and time-to-event (PFS and duration of response [DOR]) outcomes. Safety outcomes included cytokine release syndrome (CRS), neurological events (NE), infections, prolonged cytopenia, and use of corticosteroids or tocilizumab for CRS management. Given that TRANSCEND FL had a large proportion of patients with 3L+ R/R FL who received bridging therapy (N = 44 [41%]) versus ZUMA-5 (N = 4 [3%]), the primary analysis excluded liso-cel patients who received bridging therapy. Comparison with tisa-cel included all liso-cel patients, as the proportion of patients who received bridging therapy was similar (tisa‑cel, N = 44 [47%]).
Baseline characteristics and outcome measures in TRANSCEND FL were redefined to align with those reported in ZUMA-5 and ELARA. Data from TRANSCEND FL were weighted using a method-of-moments propensity score model to match the marginal distribution of clinical factors among patients from ZUMA-5 and ELARA, respectively. A panel of clinicians selected clinical factors separately for efficacy and safety endpoints. The key factors adjusted for included FL International Prognostic Index risk factor, bulky disease, age, prior lines of therapy, R/R status, progression of disease ≤ 24 months, ECOG PS, bridging therapy, prior ASCT, lymphoma present in bone marrow, sex, and histology subtype (grade 1, 2, or 3a). Response ratios (RR), hazard ratios (HR), and odds ratios (OR) with corresponding 95% CIs were used to compare response outcomes, time-to-event outcomes, and safety outcomes, respectively.
Results: Compared with axi-cel, liso-cel demonstrated an improved CR rate (RR, 1.25; 95% CI, 1.09–1.45) and a comparable ORR (RR, 1.06; 95% CI, 1.00–1.12), PFS (HR, 1.14; 95% CI, 0.47–2.74), and DOR (HR, 1.26; 95% CI, 0.52–3.05). Liso-cel also exhibited a more favorable safety profile versus axi-cel, with lower odds of any-grade NEs (OR, 0.16; 95% CI, 0.06–0.45), any-grade infections (OR, 0.37; 95% CI, 0.14–0.93), and tocilizumab use for CRS management (OR, 0.30; 95% CI, 0.10–0.91). Trends of reduced odds of any-grade CRS (OR, 0.72; 95% CI, 0.31–1.69), grade ≥ 3 CRS (OR, 0.14; 95% CI, 0.02–1.23), corticosteroid use for CRS management (OR, 0.31; 95% CI, 0.06–1.57), grade ≥ 3 infections (OR, 0.67; 95% CI, 0.17–2.65), and prolonged cytopenia (OR, 0.52; 95% CI, 0.18–1.47) were observed in favor of liso-cel but were not statistically significant.
Compared with tisa-cel, liso-cel demonstrated an improved CR rate (RR, 1.33; 95% CI, 1.06–1.68) and a comparable ORR (RR, 1.09; 95% CI, 0.95–1.25), PFS (HR, 0.62; 95% CI, 0.21–1.87), and DOR (HR, 0.47; 95% CI, 0.14–1.65). For safety outcomes, liso-cel showed a trend towards reduced odds of any-grade NEs (OR, 0.32; 95% CI, 0.10–1.02), grade ≥ 3 NEs (OR, 0.39; 95% CI, 0.06–2.48), any-grade infections (OR, 0.85; 95% CI, 0.25–2.87), and use of corticosteroids (OR, 0.94; 95% CI, 0.11–7.73) or tocilizumab (OR, 0.68; 95% CI, 0.19–2.41) for CRS management.
Conclusions: After adjusting for intertrial differences, liso-cel showed a higher CR rate compared with axi-cel and tisa-cel, respectively, and comparable efficacy for ORR, PFS, and DOR. Liso-cel had a more favorable safety profile compared with axi-cel and a similar safety profile compared with tisa-cel, with a trend favoring liso-cel for reduced medication use in CRS management, any-grade infections, and NEs.
Disclosures: Boardman: Bristol Myers Squibb: Consultancy; Cancer Study Group, LLC: Consultancy; OncLive: Honoraria. Reguera: Kite/Gilead: Consultancy; Amgen: Speakers Bureau; Incyte: Speakers Bureau. Spin: EVERSANA: Current Employment. Wang: Eversana: Consultancy, Current Employment. Almuallem: EVERSANA: Current Employment. Ellis: EVERSANA: Current Employment. Zheng: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Kumar: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Farazi: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Martín García-Sancho: AbbVie: Consultancy, Honoraria; Roche: Honoraria, Other: Travel and Accommodation Support; Incyte: Consultancy, Honoraria; Kyowa Kirin: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria, Other: Travel and Accommodation Support; Lilly: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Genmab: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Takeda: Honoraria; Janssen: Consultancy, Honoraria, Other: Travel and Accommodation Support; IDEOGEN: Consultancy, Honoraria; Miltenyi Biotec: Consultancy, Honoraria; Novartis: Consultancy; EUSA Pharma: Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel and Accommodation Support; BeiGene: Consultancy, Honoraria. Izutsu: Beigene, Yakult, Otsuka: Consultancy, Research Funding; Ono Pharma, Symbio, Takeda: Consultancy, Honoraria; Incyte, Bayer, O Oncology, Regeneron: Research Funding; Pfizer, Janssen, Gilead, Daiichi Sankyo: Honoraria, Research Funding; MSD, AstraZeneca, Genmab, Chugai, BMS, Kyowa Kirin, Novartis, AbbVie: Consultancy, Honoraria, Research Funding; AstraZeneca, Eli Lily, Astellas, Ono Pharmaceuticals, Eisai, Chugai, Janssen, Symbio, Bristol Myers Squibb, Daiichi Sankyo, Otsuka, Abbvie, Takeda, Eli Lilly, Genmab, Kyowa Kirin, MSD, Astellas, Pfizer, MeijiSeika Pharma, Novartis, Nihon Kayaku, Gilead,: Honoraria; MSD, AstraZeneca, Abbvie, Incyte, Bristol Myers Squibb, Novartis, Bayer, Pfizer, Janssen, Yakult, Kyowa Kirin, Daiichi Sankyo, Chugai, Beigene, Genmab, LOXO Oncology, Otsuka, Regeneron, Gilead: Research Funding; AstraZeneca, Zenyaku, Ono Pharmaceuticals, Mitsubishi Tanabe Pharma, Eisai, Chugai, Bristol Myers Squibb, Takeda, Otsuka, Abbvie, Zenyaku, Kyowa Kirin, MSD, Carna Biosciences, Novartis, Yakult, Nihon Shinyaku, Abe Pharma, Eisai,Beigene: Consultancy.