FDA OKs Regulatory T-Cell Immunotherapy in Hematologic Malignancies

The FDA has approved allogeneic regulatory T-cell–containing immunotherapy with hematopoietic stem and progenitor cell (HSPC) and T cells-vldq (Tregzi; formerly Orca-T) in combination with matched hematopoietic stem cell transplantation (HSCT) and a myeloablative conditioning regimen among adult patients with hematological malignancies, according to a news release from the agency.¹ The agent is intended for hematopoietic and immunologic reconstitution and to improve chornic graft-versus-host disease (GVHD)–free survival (GFS) among patients.

Supporting data for the approval came from the phase 3 Precision-T trial (NCT05316701), which assessed the agent among 187 patients with acute leukemias or myelodysplastic syndromes (MDS). The median chronic GFS was not estimable (NE) (95% CI, NE-NE) in the experimental arm (n = 93) vs 7.3 months (95% CI, 6.3-15.5) in the control arm, in which patients were assigned to receive unmanipulated allograft followed by GVHD prophylaxis with tacrolimus (Prograf) and methotrexate (n = 94; HR, 0.26; 95% CI, 0.14-0.47; P <.00001). Additionally, the estimated 12-month cumulative rates of moderate-to-severe chronic GVHD were 12.6% (95% CI, 5.3%-23.1%) vs 44.0% (95% CI, 31.3%-56.1%) in each respective arm (HR, 0.19; 95% CI, 0.08-0.43; P = .00002).

All patients (100%) in the experimental arm experienced a neutrophil count of 500/mm³ within 4 weeks of infusion, which included 53 (60.2%) with neutrophil counts exceeding 500/mm³ for 3 consecutive days.

Common adverse effects reported in the experimental arm included mucositis, diarrhea, rash, viral infections, infections-pathogen unspecified, abdominal pain, vomiting, nausea, bacterial infections, hemorrhage, and acute GVHD. Additionally, the prescribing information details warnings and precautions for graft failure, GVHD, infusion reactions, secondary malignancies and malignancies of donor origin, and transmission of infectious agents.

The newly approved product consists of 3 sequentially administered components: HSPCs at a minimum of 1.0 x 10⁶ cells/kg plus regulatory T cells at 1.3 x 10⁶ to 3.5 x 10⁶ cells/kg on day 0 followed by conventional T cells at 1.3 x 10⁶ to 6.9 x 10⁶ cells/kg at 2 or 3 days afterwards.

“This is another important step forward in making allogeneic transplant, which is still an incredibly important yet very fraught procedure to potentially cure these very high-risk leukemias, a safer and more effective process,” Wendy Stock, MD, stated in an interview with CancerNetwork^® ahead of the approval. “Given the safety data, the efficacy data, and the promise of this approach for future generations of patients, while potentially even optimizing it more with even more cell-specific therapies, it is a great step forward.”

Stock is the Anjuli Seth Nayak Professor of Medicine, cochair of the Leukemia Committee for the National Cancer Institute–supported Alliance for Clinical Trials in Oncology, and a coleader of the Clinical and Experimental Therapeutics Research Program at the University of Chicago Medicine Comprehensive Cancer Center.

The FDA previously granted priority review to this therapy in October 2025 as a treatment for those with acute myeloid leukemia, acute lymphoblastic leukemia, and MDS undergoing HSCT in October 2025.²

References

1. FDA approves allogeneic regulatory T cell-based immunotherapy with HSPC and T cells-vldq for use in matched donor hematopoietic stem cell transplantation for adults with hematologic malignancies. News release. FDA. June 30, 2026. Accessed June 30, 2026. https://tinyurl.com/38s3wznr
2. Orca Bio announces FDA acceptance and priority review of the biologics license application (BLA) for Orca-T to treat hematological malignancies. News release. Orca Bio. October 6, 2025. Accessed June 30, 2026. https://tinyurl.com/urwb7244