Dr. Amandeep Salhotra on the Efficacy and Safety of Orca-Q in GVHD

Amandeep Salhotra, MD, hematologist-oncologist, associate professor, Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, discusses efficacy data from a phase 1 trial (NCT03802695) of Orca-Q in acute and chronic graft-vs-host disease (GVHD).

In this non-randomized, 3-armed study, the next-generation investigational cell therapy Orca-Q was evaluated in patients with hematologic malignancies who were undergoing myeloablative allogeneic hematopoietic stem cell transplantation (HSCT). Study arms included a matched donor arm, a haploidentical arm, and a non-GVHD prophylactic arm.

In the haploidentical arm, single-agent tacrolimus was administered as prophylaxis in place of posttransplant cyclophosphamide (PTCy), Salhotra notes. Patients who developed acute GVHD were typically treated with a 3 to 5-day course of steroids, he says. The median duration of follow-up was approximately 200 days, with 9 patients experiencing over a year of follow-up.

Results from the haploidentical arm of this study were presented at the 2022 ASH Annual Meeting, showing that Orca-Q reduced the rates of both acute and chronic GVHD, Salhotra says. Additionally, the 1-year GVHD relapse-free survival (GRFS) rate was 75% for the Orca-Q plus tacrolimus arm vs 46% with ASCT plus PTCy. A comparison of GRFS rate vs PTCy therapy shows a 30% increase in composite outcome.

The depletion of specific T-cell subsets during manufacturing of Orca-Q can lead to the development of GVHD in some patients, Salhotra qualifies. However, this unique manufacturing has largely proven effective in reducing both acute and chronic GHVD, and preventing relapse, Salhotra explains. Moreover, no patients had developed moderate to severe chronic GVHD at the time of median follow-up, he emphasizes.

Most patients experienced neutrophil engraftment at 12 days and platelet engraftment at 16 days, Salhotra continues. However, 2 patients experienced engraftment failures, while 1 patient was able to successfully receive subsequent salvage transplant, and the other developed fungal pneumonia and passed, Salhotra notes.

Another important outcome was the low incidence of cytokine release syndrome (CRS), Salhotra says. CRS is often observed following infusion, resulting in treatment with antibiotics, more workup, and occasionally fluid resuscitation or transfer to an intensive care unit, he details. However, CRS greater than grade 2 was infrequently observed and easily managed with antidiuretic medications, Salhotra concludes.