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.