denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Type: Oral
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Treating Refractory Disease-Novel Agents and Quality-of-Life
Hematology Disease Topics & Pathways:
Research, Clinical trials, Lymphoid Leukemias, Combination therapy, Adult, CLL, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, B Cell lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Study Population, Human
Methods: Eligible pts ≥ 18 y of age with CLL/SLL had ≥ 1 of the following: 1) receiving BTKi with PD at entry, 2) high-risk disease and < CR after ≥ 6 mo on BTKi, 3) BTK/PLCγ2 mutation ± ibr PD, 4) prior BTKi with no contraindications to ibr, and 5) (per amendment) PD on BTKi and received prior venetoclax. At enrollment, pts started or continued ibr (420 mg daily or less for toxicity) through leukapheresis and for up to 90 d (or longer per investigator [inv]) after liso‑cel (target dose of 50 × 106 CAR+ T cells [DL1] or DL2). Response was per inv by 2018 iwCLL criteria. Primary endpoint was CR/CRi rate at DL2; secondary endpoints included safety, ORR, duration of response (DOR), duration of CR/CRi (DOCR), time to response, time to CR/CRi, PFS, OS, and undetectable MRD (uMRD) rate in blood. Cellular kinetics was exploratory. Efficacy analyses were at DL2 and safety at DL1 + DL2. Treatment-emergent AEs (TEAE) occurred the latter of ≤ 90 days after liso-cel or ≤ 30 days of ibr completion. Liso-cel–treated pts who completed or withdrew from study could enroll in a separate long-term follow-up (LTFU) study (NCT03435796) for safety and OS ≤ 15 y after liso‑cel.
Results: A total of 65 pts underwent leukapheresis; 56 received ibr + liso-cel (DL1, n = 5; DL2, n = 51). At data cutoff (01/12/2024), 28 of 56 (50%) pts had discontinued the study, 11 (20%) completed the study, and 17 (30%) were ongoing; 5 of 28 (18%) eligible pts enrolled in LTFU. Median (IQR) on-study follow-up (including LTFU) was 24.8 mo (14.2–34.6). Median (range) age was 65 y (44–77); 55 (98%) pts had high-risk cytogenetics, such as del(17p) (n = 25), TP53 mutation (n = 24), and unmutated IGHV (n = 39); 43% had LDH ≥ ULN; and median (range) SPD was 27 cm2 (1–218). Pts had a median (range) of 5 (1–13) prior therapies (≤ 2, n = 13 [23%]). Median (range) time from leukapheresis to liso-cel availability was 25 d (17–79). Median (range) ibr exposure was 34 d (15–188) before and 94.5 d (6–1517) after liso-cel.
At DL2, ORR (95% CI) was 86% (73.7–94.3), median (range) time to first response was 1.0 mo (0.9–6.0), and median (95% CI) DOR was 41.4 mo (23.3–not reached [NR]). CR/CRi rate (95% CI; primary endpoint) was 45% (31.1–59.7), median (range) time to first CR/CRi was 3.1 mo (0.9–12.1), and median (95% CI) DOCR was NR (26.6–NR). Median (95% CI) PFS and OS was 31.4 mo (20.1–NR) and NR (27.5–NR), respectively. uMRD rate (95% CI) in blood and marrow was 86% (73.7–94.3) and 84% (71.4–93.0), respectively.
Grade (gr) ≥ 3 TEAEs occurred in 48 (86%) pts (most commonly neutropenia [52%] and anemia [41%]) with no gr 5 TEAEs. Liso-cel–related gr ≥ 3 TEAEs occurred in 32 (57%) pts and ibr-related gr ≥ 3 TEAEs in 24 (43%) pts including cardiovascular events of hypertension (7%) and atrial fibrillation (2%). Any-gr CRS occurred in 45 (80%) pts (gr ≥ 3, n = 2 [4%]) and any-gr neurological events (NE) in 23 (41%) pts (gr ≥ 3, n = 6 [11%]). Eight (14%) pts had gr ≥ 3 infections and 5 (9%) had second primary malignancies. Twenty-five (45%) pts had prolonged cytopenias (gr ≥ 3 at D30); most recovered to gr ≤ 2 by D90. Sixteen pts died after infusion (PD, n = 6; unknown, n = 6; COVID-19, n = 3; mixed septic/cardiogenic shock, n = 1). Liso‑cel showed rapid expansion (median tmax, 10 d) and was detected up to 42 mo after infusion.
Conclusions: Combined liso-cel + ibr demonstrated substantial efficacy with deep remissions (86% ORR, 45% CR rate, and 86% blood uMRD rate) and manageable safety in pts with R/R CLL/SLL. Though comparisons should be made with caution and there were differences in disease characteristics between cohorts, liso-cel + ibr showed a numerically higher ORR/CR rate and lower gr ≥ 3 CRS/NE rates vs liso-cel monotherapy, supporting the combination as a promising new therapeutic strategy for pts with R/R CLL/SLL.
Disclosures: Wierda: GSK: Research Funding; F. Hoffmann-La Roche Ltd.: Research Funding; AstraZeneca: Research Funding; Cyclacel Pharmaceuticals Inc: Research Funding; BMS: Research Funding; Janssen: Research Funding; Juno Therapeutics: Research Funding; Gilead Sciences: Research Funding; Oncternal Therapeutics: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Nurix Therapeutics: Research Funding; Loxo Oncology: Research Funding; Eli Lilly: Research Funding; Numab Therapeutics: Research Funding; Accutar Biotechnology: Research Funding; Novartis: Research Funding; Oncternal Therapeutics: Research Funding; National Comprehensive Care Center (NCCN): Other: Financial relationship (Chair, CLL); Kite: Research Funding; Acerta Pharma: Research Funding; Genentech, Inc.: Research Funding; AbbVie: Research Funding. Dorritie: Janssen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Kite-Gilead: Research Funding; Hoffman La-Roche: Research Funding; Genmab: Research Funding. Gauthier: Century Therapeutics: Other: Independent Data Review Committee; Sobi, Juno Therapeutics (a BMS company), Celgene (a BMS company), Angiocrine Bioscience, Faron Pharmaceuticals, CARGO therapeutics: Research Funding; Sobi, Legend Biotech, Janssen, Kite Pharma, MorphoSys: Honoraria. Kipps: Abbvie/Janssen/Pharmacyclics/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lymphoma and Leukemia Society: Research Funding; Oncternal Therapeutics: Current equity holder in private company. Riedell: Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fate Therapeutics: Research Funding; Calibr: Research Funding; Cargo Therapeutics: Research Funding; Tessa Therapeutics: Research Funding; Sana Biotechnology: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Intellia Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics: Research Funding; Xencor: Research Funding; CVS Caremark: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Adaptive Biotechnologies: Honoraria. Eradat: AbbVie/Pharmacyclics, BeiGene, Genentech, Incyte, MorphoSys: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca, Atara, BMS, Gilead/Kite, Juno: Research Funding. Kenderian: Novartis, Kite/Gilead, Juno/BMS, Capstan, Humanigen, Carisma: Membership on an entity's Board of Directors or advisory committees; Novartis, Kite/Gilead, Juno/BMS, Lentigen, Humanigen, Morphosys, Tolero, LeahLabs, InCyte, Viracta: Research Funding; Novartis, Humanigen, MustangBio,: Patents & Royalties; Kite/Gilead, Novartis, Carisma, Juno/BMS, Humanigen, Luminary: Consultancy. Kharfan-Dabaja: Kite Pharma: Honoraria; Pharmacyclics: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Research Funding. Shah: Miltenyi Biomedicine, Lilly Oncology: Research Funding; Gilead-Kite, BMS-Juno, Miltenyi, Lilly Onclogy, Novartis, Seattle Genetics, Janssen, Abbvie, Cargo, Beigene, Galapagos, AstraZeneca: Consultancy, Honoraria; Tundra Therapeutics: Current holder of stock options in a privately-held company. Ermann: AstraZeneca: Speakers Bureau; Beigene, ADC therapeutics: Consultancy. Arnason: BMS: Other: Speaker fees; Regeneron Pharmaceuticals, Inc.: Other: Speaker fees. Deol: Janssen: Consultancy; Kite, a Gilead Company: Consultancy; Adicet Biotherapeutics: Consultancy. Feldman: Seagen: Consultancy, Speakers Bureau; AbbVie, AstraZeneca, Epizyme, Genmab, Gilead/Kite, Karyopharm, Takeda: Consultancy. Andreadis: Roche: Research Funding; Genmab: Research Funding; Seattle Genetics: Consultancy; Merck: Research Funding; BMS: Consultancy; Gilead/Kite: Consultancy; Abbvie: Consultancy; Astra Zeneca: Consultancy; Novartis: Research Funding. Ghosh: Cargo: Consultancy; BMS: Consultancy; Kite/Gilead: Research Funding; Novartis: Research Funding; Cabaletta Bio: Consultancy, Research Funding. Ma: AstraZeneca: Consultancy, Research Funding, Speakers Bureau; BeiGene: Consultancy, Research Funding, Speakers Bureau; Lilly: Research Funding, Speakers Bureau; Janssen: Consultancy; Juno: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Gergis: Moderna: Current equity holder in publicly-traded company; Biontech: Current equity holder in publicly-traded company; Jazz: Other: Travel Support, Speakers Bureau; Autolus: Consultancy; Astellas: Other: Travel Support, Speakers Bureau; Kite: Other: Travel Support, Speakers Bureau; Incyte: Other: Travel Support, Speakers Bureau; Iovance: Current equity holder in publicly-traded company; VOR: Consultancy. Vose: Novartis: Honoraria; Abbvie: Honoraria, Research Funding; GenMab: Honoraria, Research Funding; Pfizer: Research Funding. Soumerai: Moderna: Research Funding; LOXO@Lilly: Consultancy; Roche/Genentech: Consultancy, Research Funding; BostonGene: Research Funding; Beigene: Consultancy, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Adaptive Biotechnologies: Research Funding; Bristol Myers Squibb: Consultancy; GlaxoSmithKline: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding. van Besien: Morphosys: Consultancy; Intellia: Consultancy; ADC Therapeutics: Consultancy; Autolus: Consultancy; Avertix: Current equity holder in private company; Hemogenyx: Consultancy, Current equity holder in publicly-traded company; Realta: Consultancy; Astra Zeneca: Consultancy; Adbio: Consultancy; INCYTE: Consultancy; SNIPR Microbiome: Consultancy. Tuazon: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Perna: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Ou: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Rane: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Papp: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Chen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Siddiqi: Gilead: Other: Ad board; Abbvie: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Speakers Bureau.
OffLabel Disclosure: Yes, lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed CAR T cell product approved for the treatment of several B-cell malignancies, including adult patients with R/R CLL/SLL who have received at least 2 prior lines of therapy including a Bruton tyrosine kinase inhibitor (BTKi) and a B-cell lymphoma 2 inhibitor. The current abstract describes a clinical study evaluating use of liso-cel concurrent with the BTKi ibrutinib in patients who have received at least 1 prior line of therapy.