Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster III
Hematology Disease Topics & Pathways:
Clinical trials, Research, Clinical Research
Select baseline characteristics between trials (FH9952 vs FH9762) were as follows: age (median 66 vs 64 yrs), ECOG 2+ performance status (12% vs 5.6%), presence of a high risk chromosomal abnormality (HRCA: 56% vs 72%; del17p, t4;14, t14;16, t14;20), ISS stage (median 2.5 vs 2.5), prior lines of therapy (median 9.5 vs 8.0), time from diagnosis to CAR-T infusion (median 5.5 vs 5.1 yrs), BMPC % at screening (45% vs 60%), EMD+ (28% vs 44%), baseline tumor BCMA level (median 620 vs 620 ABCs), prior autologous (89% vs 80%) or allogeneic stem cell transplant (HCT; 11% vs 20%), and prior anti-BCMA exposure status (39% vs 12%).
With a median follow-up of 4.8 yrs for the combined cohort (n=53), the OS and PFS were 2.7 and 1.1 years, respectively. Median OS and PFS were shorter for pts with plasma cell leukemia (PCL; OS: 1.0 vs 2.8 yrs, p=.019; PFS: 0.5 vs 1.3 yrs, p=.064), extramedullary disease (EMD; OS: 1.4 vs 4.2 yrs, p=.002; PFS: 0.5 vs 1.7 yrs, p=.045), and prior BCMA exposure (OS: 1.0 vs 3.5 yrs, p=.005; PFS: 0.5 vs 1.7 yrs, p=.0001); but not for pts with a HRCA (OS: 2.7 vs 2.3 yrs, p=.81; PFS: 1.5 vs 1.0 yrs, p=.72).
For FH9952 vs FH9762, the median OS (3.1 vs 2.6 yrs, p=.48) and PFS (0.9 vs 1.3 yrs, p=.72) were similar. In univariate (UV) Cox regression, factors associated with OS included prior BCMA exposure (HR 3.02, 95% CI 1.35-6.79, p=.007), EMD (HR 3.06, 95% CI 1.44-6.50, p=.004), BMPC % (HR 1.19, 95% CI 1.03-1.37, p=.015), PCL (HR 5.10, 95% CI 1.12-23.2, p=.035), and soluble BCMA at day +60 (HR 1.52, 95% CI 1.22-1.90, p<.001); and factors associated with PFS included prior BCMA exposure (HR 4.20, 95% CI 1.89-9.36, p<.001), EMD (HR 1.93, 95% CI 1.00-3.72, p=.049), BMPC % (HR 1.26, 95% CI 1.09-1.45, p=.001), and day +60 soluble BCMA (HR 1.69, 95% CI 1.27-2.25, p<.001).
Among BCMA-naïve pts (n=33), the median OS was significantly longer for FH9952 vs FH9762 (NR vs 2.3 yrs, p=.033), though PFS differences did not achieve statistical significance (2.6 vs 1.4 yrs, p=.11); 2-yr point estimates were 64% vs 36% for PFS and 91% vs 59% for OS. In UV Cox regression restricted to BCMA-naïve pts, FH9952 was associated with lower hazard of OS (ref: FH9762; HR 0.32, 95% CI 0.11-0.96, p=.043), but not PFS (ref: FH9762; HR 0.64, 95% CI 0.30-1.39, p=.3). In an exploratory multivariate analysis that included the receipt of GSI and screening BCMA levels (modeled as a restricted cubic spline) with an interaction term, we observed increasing HRs of PFS and OS at low BCMA densities (<760 ABC) in pts who did not receive a GSI.
Rates of ASTCT defined CRS (G1+: 94% vs 84%, p=.4; G3+: 11% vs 4%, p=.6) and ICANS (G1+: 39% vs 20%, p=.2; G3+: 11% vs 0%, p=.2) did not achieve statistical significance, but were numerically higher for FH9952 compared to FH9762.
The BCMA CAR-T product, FCARH143, demonstrated clinical activity and manageable toxicity in two heavily pretreated R/R MM cohorts. Pts with known high-risk features (i.e., PCL, EMD, prior BCMA exposure) and increasing day +60 soluble BCMA experienced worse long-term outcomes. Among BMCA-naïve pts, those who received a GSI experienced significantly longer OS compared to those who received FCARH143 alone. Receipt of GSI may have the largest effect on PFS/OS in patients with low baseline BCMA tumor density levels. Limitations of this study include a small sample size and retrospective analysis. A randomized prospective study is needed to confirm a survival benefit of incorporating a GSI into treatment with FCARH143, or other BCMA CAR-T products.
Disclosures: Tuazon: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Pont: Lyell Immunopharma: Current equity holder in publicly-traded company; Galapagos: Current Employment, Current holder of stock options in a privately-held company. Cole: Galapagos BV, the Netherlands: Current Employment. Wood: Amgen: Consultancy; Cellnomics LLC: Current equity holder in private company. Blake: Sonoma Biotherapeutics: Current Employment. Works: Shape Therapeutics: Current Employment. Shadman: Koi Biotherapeutics: Current holder of stock options in a privately-held company; Bristol Myers Squibb (spouse): Current Employment; Merck: Consultancy; Nurix: Consultancy; Fate therapeutics: Consultancy; Eli Lilly: Consultancy; Kite Pharma: Consultancy; Morphosys/Incyte: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; BeiGene: Consultancy, Research Funding; Janssen: Consultancy; Genmab: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Mustang Bio: Research Funding; Vincerx: Research Funding. Turtle: Caribou Biosciences: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; eGlint: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Eureka Therapeutics: Current holder of stock options in a privately-held company; Abbvie: Consultancy; IGM Biosciences: Consultancy; Myeloid Therapeutics: Current holder of stock options in a privately-held company; T-CURX: Membership on an entity's Board of Directors or advisory committees; Kyverna: Membership on an entity's Board of Directors or advisory committees; Juno Therapuetics, a BMS company: Research Funding; Cargo Therapeutics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Differentia Bio: Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Research Funding; ArsenalBio: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Boxer Capital: Consultancy; Advesya: Membership on an entity's Board of Directors or advisory committees; Prescient Therapeutics: Consultancy; ArsenalBio: Current holder of stock options in a privately-held company; Century Therapeutics: Consultancy; Myeloid Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene, a BMS company: Membership on an entity's Board of Directors or advisory committees. Till: Mustang Bio: Consultancy, Patents & Royalties, Research Funding; Bristol Myers Squibb: Research Funding; Proteios Technology: Consultancy, Honoraria. Maloney: Celgene: Research Funding; Juno Therapeutics: Patents & Royalties: rights to royalties from Fred Hutch for patents licensed to Juno, Research Funding; Novartis: Honoraria; Navan Technologies: Current equity holder in private company, Honoraria; Lyell Immunopharma: Honoraria; Interius: Honoraria; ImmPACT Bio: Honoraria; Gilead Sciences: Honoraria; Chimeric Therapeutics: Honoraria; Kite, a Gilead Company: Consultancy, Research Funding; Janssen: Consultancy; Genentech: Consultancy, Honoraria; Caribou Biosciences: Consultancy; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Legend Biotech: Research Funding; A2 Biotherapeutics: Current holder of stock options in a privately-held company. Riddell: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Nohla: Membership on an entity's Board of Directors or advisory committees; Lyell Immunopharma: Current equity holder in publicly-traded company; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Outpace: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Cowan: Caelum: Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; Juno/Celgene: Research Funding; HopeAI: Consultancy, Current holder of stock options in a privately-held company; Abbvie: Research Funding; Harpoon: Research Funding; Nektar: Research Funding; IgM biosciences: Research Funding; Regeneron: Research Funding; Sanofi: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sebia: Consultancy. Green: Janssen Pharmaceuticals: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Ensoma: Consultancy; SpringWorks Therapeutics: Research Funding; Juno Therapeutics, A Bristol Myers-Squibb Company: Patents & Royalties, Research Funding.