Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Biological therapies, clinical trials, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Clinical Research, Diseases, Therapies, Lymphoid Malignancies
Methods: Eligible patients had MM, received 1 prior line of therapy (proteasome inhibitor and immunomodulatory drug required), had early disease progression (≤12 mo after ASCT or ≤12 mo after start of anti-myeloma therapy for patients who did not undergo ASCT), and were treatment-naive to CAR-T/anti-B-cell maturation antigen (BCMA) therapies. Bridging therapy was allowed between apheresis and CAR-T cell infusion. A single cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg) was given post lymphodepletion. Safety and efficacy were assessed. The primary endpoint was minimal residual disease (MRD) negativity by next generation sequencing at 10-5. Management strategies were implemented to minimize risk of movement/neurocognitive treatment-emergent adverse events (MNTs)/parkinsonism. Pharmacokinetics, CAR-T cell phenotype, and cytokine profiles are also being investigated.
Results: As of June 1, 2022, 19 patients (median age 58 years [range 44–67]; 74% male; 16% high-risk cytogenetics, 63.2% standard risk, 21.1% unknown) received cilta-cel and 16 remained on study. Median follow-up was 17.8 months (range 5.2–26.3). 79% of patients received prior ASCT. Overall response rate was 100%, with 100% achieving very good partial response or better, and 90% achieving complete response or better (Figure). Median time to first response and best response were 0.95 months (range 0.9 – 9.7) and 5.1 months (range 0.9 – 11.8), respectively. Of patients who were MRD-evaluable (n= 15), 14 (93 %) achieved MRD 10-5 negativity during the study. Median DOR was not reached and 12-month event-free rate was 84%. The 12-month progression-free survival rate was 90%. Most common treatment-emergent AEs were hematologic (grade 3/4: neutropenia, 90%; lymphopenia, 42%; thrombocytopenia, 26%; leukopenia, 26%). Median time from cilta-cel infusion to onset of cytokine release syndrome (CRS) was 8 days (range 5–11) and occurred in 16 (84.2%) patients (grade 4, n=1). CRS resolved in all patients. Immune effector cell-associated neurotoxicity syndrome (grade 1) occurred in 1 patient and Movement and neurocognitive TEAEs/parkinsonism (grade 3) occurred in 1 patient (previously reported). Three patients died post cilta-cel at days 158, 417, and 451 due to progressive disease. Levels of interleukin (IL)-6, interferon gamma, IL-2Rα, and IL-10 increased post infusion, peaked at days 7–14, coincident with the timing of CRS, and returned to baseline levels within 2–3 months post infusion.
Conclusions: In this functionally high-risk patient population, all of whom relapsed within a year of treatment with standard of care upfront therapy (including 79% with ASCT), 90% remained progression-free at 1 year post cilta-cel infusion. Results at this longer (18 months) follow-up show durability and deepening of response to cilta-cel and maintenance of PFS rate. This represents a potentially significant advancement in a population with high unmet need.
Disclosures: Van De Donk: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Agha: GenCART Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Cohen: Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Ichnos, Janssen Oncology, Oncopeptides, Pfizer, Seattle Genetics, Genentech/Roche, AstraZeneca, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline and Novartis: Research Funding; Novartis: Patents & Royalties: CAR T-cells and biomarkers of cytokine-release syndrome. Cohen: Medison: Honoraria; GSK: Honoraria; Takeda: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Amgen: Honoraria, Research Funding; Neopharm: Honoraria. Roeloffzen: Amgen: Honoraria; Sanofi: Honoraria; Bristol Myers Squibb: Honoraria; Janssen: Honoraria. Madduri: Janssen: Current Employment; Amgen, Allogene, BMS, Celgene: Research Funding; BMS, Takeda, GSK, Kinevant, Legend, Sanofi, Celgene: Consultancy. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. De Braganca: Janssen R&D: Current Employment. Jackson: Janssen R&D: Current Employment. Varsos: Janssen: Current Employment. Roccia: Janssen: Current Employment, Current equity holder in publicly-traded company. Li: Janssen R&D, a Johnson and Johnson company: Current Employment, Current equity holder in publicly-traded company. Zudaire: Janssen R&D, Johnson and Johnson: Current Employment. Corsale: Janssen R&D: Current Employment. Geng: Legend Biotech USA: Current Employment. Pacaud: Legend Biotech USA: Current Employment. Sonneveld: Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Zweegman: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding.
OffLabel Disclosure: Cilta-cel is a CAR-T therapy approved for patients with relapsed/refractory multiple myeloma after 4 or more lines of therapy.