No moderate-to-severe chronic graft-versus-host disease (GVHD) occurred in patients with high-risk hematologic malignancies who received Orca-Q, an investigational precision-engineered cell therapy.
Amandeep Salhotra, MD, of the Beckman Research Institute at the City of Hope National Medical Center, and colleagues conducted the study of Orca-Q and presented their findings at the 64th American Society of Hematology Annual Meeting and Exposition.
They conducted the study due to the high rates of GVHD and relapse in patients after allogeneic hematopoietic stem cell transplantation (HSCT) with haploidentical related donors, and the association between post-transplant cyclophosphamide and a high incidence of cytokine release syndrome and infections.
Due to those factors, Orca-Q represents an “alternative strategy, which may be administered with single-agent prophylaxis and does not require [post-transplant cyclophosphamide],” Dr. Salhotra and colleagues wrote.
“The cellular composition of Orca-Q consists of enriched CD34+ stem cells combined with specific T-cell subsets and is intended to reconstitute the blood and immune systems,” Dr. Salhotra and colleagues noted. “Orca-Q is hypothesized to reduce GVHD, relapse, and serious infections.”
The investigators enrolled adults aged 18 to 65 years who had high-risk hematologic malignancies and underwent myeloablative conditioning and allogeneic HSCT between January 2019 and July 2022.
Patients received single-agent tacrolimus on the day before treatment until day 60 after treatment as GVHD prophylaxis. Approximately two-thirds of patients received total body irradiation (TBI)-based myeloablative conditioning regimens, with the remaining patients receiving non-TBI-based myeloablative conditioning. Post-transplant cyclophosphamide was not permitted.
The Orca-Q drug product, which was manufactured centrally from granulocyte-colony-stimulating, factor-mobilized, peripheral blood apheresis, was “successfully manufactured and delivered to all subjects with a vein-to-vein time of less than 72 hours,” according to Dr. Salhotra and colleagues.
The analysis included 21 patients who had at least 30 days of follow-up data. Of the 21 patients, 11 had acute myeloid leukemia, 8 had acute lymphoblastic leukemia, and 2 had chronic myeloid leukemia in blast crisis. All were 4/8 human leukocyte antigen matched. The median patient age was 44 years.
The median neutrophil engraftment time was 13 days, whereas the median platelet engraftment time was 16 days. The 1-year estimated incidence of grade III infections as defined by the Blood and Marrow Transplant Clinical Trials Network was 27%.
The researchers estimated the 6-month incidence of grade II-IV acute GVHD was 14%, which “compares favorably with literature reports of 21%-63% [grade II-IV acute] GVHD in patients undergoing [haploidentical] transplant with [post-transplant cyclophosphamide]-based prophylaxis,” they wrote.
The 1-year GVHD-and-relapse-free survival rate was 71%. Only 1 of the 16 patients with at least 3 months of follow-up developed mild chronic GVHD, and no patients had moderate-to-severe GVHD, which was a “notable improvement compared to historic rates of 24% to 31% for moderate-to-severe [chronic] GVHD with [post-transplant cyclophosphamide], despite the fact that Orca-Q patients receive only single-agent GVHD prophylaxis,” Dr. Salhotra and colleagues wrote.
Only 1 case of grade III acute GVHD was reported, and no cases of grade IV acute GVHD occurred. Disease relapse occurred in 2 patients. There was a total of 5 deaths, 2 of which were due to relapse.
“Initial Orca-Q data demonstrates good clinical outcomes with single agent tacrolimus and no [post-transplant cyclophosphamide] or [mycophenolate mofetil],” Dr. Salhotra and colleagues concluded. “Patients treated with Orca-Q experienced a low adverse event profile, low incidence and severity of both [acute] GVHD and [chronic] GVHD, and improved [GVHD-and-relapse-free survival] rates, offering a potential new treatment option for patients undergoing [haploidentical allogeneic] HSCT. This phase I study of Orca-Q continues to enroll patients with [haploidentical] donors across the US.”
Salhotra A, Srour SA, Hoeg RT, et al. Orca-Q demonstrates favorable GvHD-and-relapse-free survival in haploidentical transplants without post-transplant cyclophosphamide. Abstract #769. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.