Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, Biological therapies, epidemiology, Clinical Research, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, registries, Lymphoid Malignancies
Methods: RI was defined as creatinine clearance (CrCl) < 50 ml/min at the time of CAR-T therapy. CrCl of < 30 ml/min or being on dialysis was defined as severe RI. Dosing of lymphodepletion chemotherapy and grading/management of toxicities was per institutional guidelines, while responses were graded based on the IMWG response criteria.
Results: The study cohort includes 211 patients receiving ide-cel from 11 medical centers, of which 28 (13%) patients had RI at the time of CAR-T therapy with CrCl < 50 ml/min. Among these, 11 (39%) patients had severe RI including one patient on dialysis. Table 1 describes baseline and treatment characteristics of patients with and without RI. Patients with RI were older (69 vs 63 years, p=0.003) and more likely to be female (68% vs 35%, p=0.001). They had lower albumin, higher beta-2-microglobulin (B2M) and higher likelihood of having revised ISS stage 3 disease, driven primarily by high B2M levels. Median prior lines of therapy in patients with and without RI was 8 vs 6, respectively. Fludarabine was dose reduced in 82% patients with RI and amongst this group 61% of patients had > 20% dose reduction. There was no difference in CAR-T cell dose infused (median: 416 vs 408 million cells).
Cytokine release syndrome (CRS) was seen in 89% vs 84%, p=0.7 of patients with and without RI, including grade ≥ 2 CRS in 14% vs 20%, p=0.6 of patients, respectively. Neurotoxicity was observed in 21% vs 19%, p=0.7 of patients, respectively. Patients with RI had a longer hospital stay (median 13 vs 9 days, p=0.05), although ICU admission rates were similar (14% vs 7%, p=0.3). Infections were seen in 43% vs 32%, p=0.2 of patients, respectively. At one month, any ≥ grade 3 cytopenia was more common in patients with RI (86% vs 55%, p=0.001), including grade ≥ 3 neutropenia (54% vs 33%, p=0.04) and grade ≥ 3 thrombocytopenia (75% vs 41%, p<0.001). By 90 days post CAR-T, there was no difference in > grade 3 cytopenias amongst the 2 groups. Renal function did not significantly change after CAR-T in most patients. Amongst patients with paired baseline and day 30 data, no patient with CrCl 30-49 ml/min experienced worsening of CrCl to < 30 ml/min at day 30. Amongst 10 patients with CrCl < 30 ml/min, 3 patients experienced improvement in CrCl to 30-49 ml/min, while 7 patients had similar CrCl at day 30. New need for dialysis post CAR-T was observed in two patients, both with baseline CrCl > 50 ml/min; in one patient at 1 week post CAR-T in the setting of critical illness/severe CRS and in another patient 8 months post CAR-T in the setting of salvage therapy for relapse and critical illness. 34 patients have died by last follow-up, of which 8 were due to CAR-T related toxicities including infections (1 patient with RI, 7 without RI, p=0.9).
189 patients were evaluable for response. Patients with RI had an overall response rate of 96% comparted to 83% in patients without RI, p=0.045. Complete response (58% vs 65%, p=0.1) and very good partial response rates (77% vs 65%, p=0.2) were similar. At a median follow-up of 6 months, the median progression-free survival (PFS) in the two groups was 6.5 vs 8.1 months, p=0.6 (Fig 1). On multivariable analysis incorporating RI, age, cytogenetics and prior BCMA-directed therapy, RI was not an independent predictor for PFS (HR 1.4, 95% CI: 0.7-2.7, p=0.4), while high-risk disease, prior BCMA therapy, and age < 65 years were independent adverse prognostic factors.
Conclusions: This multicenter retrospective study supports the feasibility of ide-cel CAR-T cell therapy in RRMM patients with RI. CRS, neurotoxicity and non-relapse mortality were comparable in patients with or without RI, although patients with RI had a longer hospital stay and were more likely to experience short-term high-grade cytopenias. Importantly, patients with RI experienced similar benefit in terms of response rates and PFS.
S.S & L.P: co-first authors. L.S, K.K.P & D.K.H: joint senior authors
Disclosures: Sidana: Oncopeptides: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Allogene: Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy; Prothena: Honoraria; Magenta Therapeutics: Consultancy, Research Funding. Hashmi: Sanofi: Consultancy, Speakers Bureau; GSK: Speakers Bureau; BMS: Consultancy; KARYOPHARM: Speakers Bureau; JANSSEN: Consultancy. Ferreri: Sanofi: Membership on an entity's Board of Directors or advisory committees; Affimed: Current equity holder in publicly-traded company. Atrash: GSK: Honoraria, Research Funding; Celgene: Honoraria, Speakers Bureau; Takeda: Honoraria; Sanofi: Honoraria, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Research Funding. Simmons: Kite/Gilead: Speakers Bureau. Arai: Kadmon: Membership on an entity's Board of Directors or advisory committees. Miklos: Bristol Meyers Squibb: Consultancy; Allogene: Research Funding; Fosun Kite: Consultancy, Honoraria; Pharmacyclics: Patents & Royalties: cGVHD Ibrutinib patent ; Novartis: Consultancy; Kite, a Gilead Company: Research Funding; Adaptive Biotech: Consultancy; Janssen: Consultancy, Honoraria. Wagner: Abbvie Inc.: Other: Partner is currently employed as a Medical Science Liaison . Sborov: GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Bioline: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Sanofi: Consultancy. Alsina: BMS: Research Funding; BMS, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Locke: Daiichi Sankyo: Consultancy; Takeda: Consultancy; Sana: Consultancy; CERo Therapeutics: Research Funding; ), National Cancer Institute: Research Funding; Leukemia and Lymphoma Society: Research Funding; Aptitude Health: Other: Education or editorial activity; ASH: Other: Education or editorial activity; BioPharm Communications: Other: Education or editorial activity; CAREducation: Other: Education or editorial activity; Clinical Care Options Oncology: Other: Education or editorial activity; Imedex: Other: Education or editorial activity; Society for Immunotherapy of Cancer: Other: Education or editorial activity; BMS: Research Funding; A2: Consultancy; Celgene: Consultancy; Other: Patents & Royalties: patents, royalties, other intellectual property from several patents held by the institution in my name (unlicensed) in the field of cellular immunotherapy.; Wugen: Consultancy; Umoja: Consultancy; Novartis: Consultancy, Research Funding; Legend Biotech: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Janssen: Consultancy; Iovance: Consultancy; GammaDelta Therapeutics: Consultancy; Emerging Therapy Solutions Gerson Lehrman Group: Consultancy; EcoR1: Consultancy; Cowen: Consultancy; Calibr: Consultancy; Cellular Biomedicine Group: Consultancy; Bristol Myers Squibb/Celgene: Consultancy; Bluebird Bio: Consultancy, Research Funding; Allogene: Consultancy, Research Funding; Amgen: Consultancy. McGuirk: In8bio, Inc.: Other: IIT Clinical Trial; Sana: Honoraria; Juno Therapeutics: Consultancy, Honoraria, Research Funding; CRISPR Therapeutics: Consultancy; Orca Bio: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Allovir: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Nextar: Consultancy, Honoraria. Patel: Legend, Pfizer, Celgene, Merck, Poseida, PrecisionBi Arcellx, Caribou, Nektar, oncopeptides: Consultancy. Hansen: BMS IMW Ide-Cel Academic Advisory Board: Membership on an entity's Board of Directors or advisory committees, Research Funding; Survivorship: Honoraria; OncLive: Honoraria.
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