Journal Information
Vol. 42. Issue S2.
Pages 279-280 (November 2020)
Share
Share
Download PDF
More article options
Vol. 42. Issue S2.
Pages 279-280 (November 2020)
464
Open Access
UPDATE OF CARTITUDE-1: A PHASE 1B/2 STUDY OF JNJ-68284528 (JNJ-4528), A B-CELL MATURATION ANTIGEN (BCMA)-DIRECTED CHIMERIC ANTIGEN RECEPTOR T (CAR-T) CELL THERAPY, IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (MM)
Visits
2164
J.G. Berdejaa, D. Maddurib, S.Z. Usmanic, I. Singhd, E. Zudaired, T.M. Yehe, A.J. Allredd, Y. Olyslagerf, A. Banerjeed, J.D. Goldberge, J. Schectere, D. Gengg, X. Wug, M.J. Carrasco-Alfonsog, S. Rizvig, F. Fanh, A. Jakubowiaki, S. Jagannathb
a Sarah Cannon Research Institute, Nashville, United States
b Mount Sinai Medical Center, New York, United States
c Levine Cancer Institute-Atrium Health, Charlotte, United States
d Janssen R&D, Spring House, United States
e Janssen R&D, Raritan, United States
f Janssen R&D, Beerse, Belgium
g Legend Biotech USA Inc., Piscataway, United States
h Nanjing Legend Biotech, Nanjing, China
i University of Chicago, Chicago, United States
Ver más
This item has received

Under a Creative Commons license
Article information
Full Text

Goals: JNJ-4528 is a CAR-T cell therapy containing 2 BCMA-targeting single-domain antibodies. We present updated CARTITUDE-1 (NCT03548207) phase 1b results with longer follow-up. Material and methods: Patients had MM per IMWG criteria, measurable disease, received ≥3 prior regimens or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and received an anti-CD38 antibody. Cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 over 3 days were used for lymphodepletion. JNJ-4528 (median: 0.73 ×106 CAR + viable T cells/kg) was given as a single infusion. Cytokine release syndrome (CRS) was graded by Lee et al. 2014 and neurotoxicity by CTCAE v5.0 and ASTCT. Response was assessed by IMWG criteria. Results: As of January 17, 2020 (median follow-up: 9 months [3–17]), phase 1b enrollment was complete (n = 29 treated; median prior lines: 5 (3–18); 76% penta-exposed, 86% triple-refractory, 31% penta-refractory, 97% refractory to last line of therapy). Most frequent adverse events (AEs) were neutropenia (100%), CRS (93%), and thrombocytopenia (93%). Grade ≥3 hematologic AEs were neutropenia (100%), thrombocytopenia (69%), and leukopenia (59%). 27 (93%) patients had CRS: 25 grade 1/2, 1 grade 3, and 1 grade 5 (day 99 subsequent to dose-limiting toxicity of prolonged grade 4 CRS). Median time to CRS onset was 7 days (2–12). 4 patients had treatment-related neurotoxicity: 3 grade 1/2 and 1 grade 3. Overall response rate was 100%, with 22 (76%) stringent complete responses (sCRs), 6 (21%) very good partial responses (VGPRs), and 1 (3%) PR. Median time to ≥CR was 2 months (1–9). 26/29 patients were progression-free, with 6-month progression-free survival rate of 93% and longest response ongoing at 15 months. 1 death due to CRS and 1 to acute myeloid leukemia (not treatment-related) occurred during the study. All 16 patients (14 sCR/2 VGPR) evaluable at 6 months were minimal residual disease-negative at 10-5 or 10-6. JNJ-4528 CAR + T cell expansion peaked at days 10-14. At 6-months’ individual follow-up, 22/28 patients had JNJ-4528 CAR + T cells below the level of quantification (2 cells/μL) in peripheral blood, suggesting CAR-T persistence in peripheral blood did not seem to correlate with deepening of response. At peak expansion, preferential expansion of CD8 + CAR-T cells with central memory phenotype was observed in peripheral blood. Discussion: CRS was manageable in most patients, supporting outpatient dosing. Conclusion: JNJ-4528 treatment yielded responses in all patients. Responses were early, deep, and durable at a low dose of CAR-T cells with 26/29 (90%) patients progression-free at median 9-months’ follow-up.

Idiomas
Hematology, Transfusion and Cell Therapy
Article options
Tools