Orca-T Shows Promise in Intermediate-/High-Risk MDS

Orca-T, a type of blood cancer therapy that is made of donor stem and immune cells, led to promising rates of relapse-free survival (RFS; time after treatment when a patient does not experience relapse), overall survival (OS; time from treatment until death of any cause), and graft-vs-host disease RFS (GRFS; time when a patient does not experience relapse or graft-versus-host disease) at one year, as well as a low incidence of GVHD in patients with intermediate- to high-risk myelodysplastic syndrome (MDS), according to data of a phase 1b study that were presented at the 2023 American Society of Hematology Annual Meeting.

At a median follow-up of 19.1 months (range, 6.3-32.2), results showed that the one-year RFS rate with Orca-T was 94%, the one-year modified GRFS was 75%, the one-year non-relapse mortality rate was 0% and the one-year OS rate was 94%.

Additionally, Orca-T was distributed and infused throughout the United States in under a 72-hour vein-to-vein time.

“Orca-T demonstrated promising results in this high-risk MDS patient population, including high RFS, low incidence of GVHD and very high OS at one year,” Dr. Arpita Gandhi, assistant professor of medicine, Division of Hematology/Medical Oncology, School of Medicine, Oregon Health and Science University, and coinvestigators wrote in the poster presented at the meeting.

Allogeneic hematopoietic cell transplant (alloHCT) is theorized to be a curative therapeutic approach for patients with MDS. At one year, the OS rate and RFS rate are approximately 65% and 69% in patients with MDS who underwent myeloablative conditioning, as seen in the RIMAC study.

However, investigational treatments, such as the allogeneic, high-precision cell therapy Orca-T, could potentially reduce alloHCT-related toxicities, which could ultimately help improve outcomes for this patient population. Orca-T comprises both stem and immune cells derived from allogenic donors; its mechanism involves leveraging highly purified, polyclonal donor regulatory T cells in order to control alloreactive immune responses.

In the phase 1b trial, investigators explored the efficacy and safety of Orca-T in patients with intermediate- to high-risk MDS who were eligible for transplant, as per the 2017 International Expert Panel recommendations.

Regarding baseline characteristics in the 16 patients, the median age was 59 years (range, 43-65) and 56% of patients were female. Patients either had a low (6%), moderate low (6%) moderate high (19%), high (44%), or very high (25%) Molecular International Prognostic Scoring System (IPSS-M) prognostic score. The baseline Hematopoietic Cell Transplantation-Specific Comorbidity Index was 0 (38%), 1 (19%), 2 (13%), 3 (19%) or 4 (13%). More than half of patients had an unrelated 8/8 HLA-matched donor relationship (56%).

Further findings showed that, at 1 year, no patients experienced grade 3 or higher acute graft-vs-host disease (GVHD). Two patients had moderate to severe chronic GVHD.

The authors noted that 1 patient who harbored a TP53 mutation and complex karyotype remained in complete response and had no active signs of acute or chronic GVHD at 500 days following alloHCT.

The multicenter, controlled, randomized, phase 3 trial is comparing Orca-T with standard of care in patients with MDS, acute myeloid leukemia, and acute lymphoblastic leukemia.

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