Allogeneic BCMA CAR T-Cell Therapy CT0596 Elicits 100% ORR in R/R Myeloma and Plasma Cell Leukemia

The allogeneic BCMA-directed CAR T-cell therapy CT0596 elicited an objective response rate (ORR) of 100% (95% CI, 63.1%-100%) in patients with relapsed/refractory multiple myeloma or primary plasma cell leukemia (pPCL), according to data from a first-in-human phase 1 study (NCT06718270) presented at the 2026 EHA Congress.¹

At the recommended dose level of 4.5 x 10⁸ CAR-positive T cells (n = 8), the best overall response was stringent complete response (sCR) in 6 patients (75.0%), very good partial response (VGPR) in 1 patient (12.5%), and partial response (PR) in 1 patient (12.5%); the CR/sCR rate was 75.0%, and the VGPR-or-better rate was 87.5%. All 8 patients achieved minimal residual disease (MRD) negativity at a sensitivity of 10^–6 at 4 weeks after effective infusion. At a median follow-up of 6.97 months, 6 patients maintained ongoing responses.

“At the recommended dose level, CT0596 demonstrated a manageable safety profile with no unexpected toxicities and promising efficacy in heavily pretreated patients with relapsed/refractory multiple myeloma and pPCL,” lead study author Juan Du, MD, PhD, and coauthors wrote in the poster.

Du is a member of the Department of Hematology, Myeloma & Lymphoma Center at Shanghai Changzheng Hospital, Naval Medical University, and the Department of Hematology at Renji Hospital, Shanghai Jiao Tong University School of Medicine, in China.

How was the first-in-human study of CT0596 designed?

CT0596 is an allogeneic BCMA-directed CAR T-cell product that also targets the NKG2A receptor to resist host natural killer cell rejection. The therapy is engineered with triple gene knockout of TRAC, B2M, and NKG2A to mitigate graft-vs-host disease (GVHD), reduce host immune rejection, and enhance antitumor activity, respectively. According to study authors, this universal approach is intended to address the high cost, lengthy manufacturing, and risk of manufacturing failure associated with autologous CAR T-cell therapy.

The first-in-human, dose-escalation study enrolled patients at least 18 years of age with relapsed/refractory multiple myeloma who had received at least 3 prior lines of therapy, and patients with relapsed/refractory pPCL who had received at least 1 prior line of therapy.^1,2 All patients were required to have measurable disease.

Using an i3+3 escalation scheme, the study evaluated CT0596 at doses of 1.5 x 10⁸, 3.0 x 10⁸, 4.5 x 10⁸, and 6.0 x 10⁸ CAR-positive T cells, and only the 8 patients treated at the recommended 4.5 x 10⁸ dose were included in this analysis.¹ Lymphodepletion consisted of fludarabine at 30 mg/m² and cyclophosphamide at 500 mg/m² for 3 consecutive days.

The median patient age was 64.5 years (range, 49-70), and 87.5% of patients were male. Six patients (75.0%) had multiple myeloma, and 2 (25.0%) had pPCL. High-risk cytogenetics were present in 62.5% of patients, 62.5% had International Staging System stage III disease, and 12.5% had extramedullary disease. Patients had received a median of 3.5 prior lines of therapy (range, 2-6), and 37.5% had undergone prior autologous stem cell transplant.

What additional efficacy and pharmacokinetic data were reported?

Among the 6 patients with multiple myeloma, 4 achieved sCR, 1 achieved VGPR, and 1 achieved PR; both patients with pPCL achieved sCR. Following the initial 4.5 x 10⁸ infusion, 5 patients experienced sCR, and 1 achieved VGPR.

One patient with R/R MM (PT01) achieved a PR with extramedullary disease and had an ongoing response at month 10 after retreatment with 4.5 x 10⁸ cells, following failure of an initial 3.0 x 10⁸ infusion. One patient with pPCL (PT04) who weighed 102 kg and received reduced-intensity lymphodepletion progressed after the initial 4.5 x 10⁸ infusion but achieved sCR after retreatment with a full lymphodepletion dose and 6.0 x 10⁸ cells.

Pharmacokinetic data demonstrated robust in vivo expansion of CT0596 with a median maximum concentration of 100,078 copies/µg of genomic DNA (gDNA; range, 262-389,586). The median time to maximum concentration was 10.5 days (range, 5-21), and the median area under the curve from time zero to the last measurable concentration was 732,105 day x copies/µg gDNA (range, 2136-4,705,799).

What did the safety analysis show?

All 8 patients experienced a treatment-emergent adverse effect (TEAE). Cytokine release syndrome (CRS) occurred in 7 patients (87.5%), all of which were grade 1 or 2, with no grade 3 or higher events reported. One patient (12.5%) developed grade 3 immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), which resolved after treatment. No cases of immune effector cell–associated neurotoxicity syndrome (ICANS) or GVHD were observed.

Grade 3 or higher hematologic treatment-related AEs occurred in all patients, including leukopenia, lymphopenia, and neutropenia (100% each), thrombocytopenia (75.0%), and anemia (37.5%). Grade 3 or higher treatment-related infections were reported in 1 patient (12.5%). Treatment-emergent serious AEs (SAEs) occurred in 4 patients (50.0%), and treatment-related SAEs occurred in 3 patients (37.5%). No patients discontinued treatment or died because of a TEAE.

References

1. Du J, Qiang W, Jin L, et al. First-in-human study of CT0596, an allogeneic BCMA CAR T in relapsed/refractory multiple myeloma and primary plasma cell leukemia: safety, efficacy, and pharmacokinetic at recommended dose. Presented at: 2026 EHA Congress; June 11-14, 2026; Stockholm, Sweden. Abstract PF784.
2. A study of CT0596 in relapsed/​refractory multiple myeloma and relapsed/​refractory plasma cell leukemia. ClinicalTrials.gov. Updated December 12, 2024. Accessed June 23, 2026. https://clinicaltrials.gov/study/NCT06718270