Novel Drug Has Survival Benefit in Stem Cell Transplant-Related GVHD

The novel cell therapy Orca-Q demonstrated early signals of relapse-free and overall survival benefits, in addition to an acceptable side effect profile, in patients undergoing haploidentical (a half-matched donor) stem cell transplantation without posttransplant cyclophosphamide, as shown in findings from a phase 1 trial.

Results from this trial were presented during the 2023 ASH Annual Meeting.

Results showed that both the graft-versus-host disease (GVHD) relapse-free survival (the time after treatment when a patient with cancer survives without symptoms or signs of the disease) rate and overall survival (the time from the start of treatment that a patient with cancer is alive) rate at one year was 82% with Orca-Q. This is in comparison to historical data with conventional posttransplant cyclophosphamide (a drug used to treat cancer by damaging the cell’s DNA to destroy cancer cells, although it may lower a patient’s immune response) for haploidentical stem cell transplantation, with recent one-year GVHD relapse-free survival rates of 46%.

“These findings show promising safety and efficacy outcomes using Orca-Q cell therapy for haploidentical transplant,” said Samer A. Srour, lead study author and assistant professor in the department of stem cell transplantation at The University of Texas MD Anderson Cancer Center in Houston, in an oral presentation during the meeting. “No safety signals in this haploidentical setting were identified.”

Standard allogeneic stem cell transplantation can be a curative approach for patients across many high-risk hematologic cancers, although access to this therapy was previously limited to those who have a fully matched donor. The introduction of posttransplant cyclophosphamide as prophylaxis (attempting to prevent a disease) for GVHD increased the utility of haploidentical donors; however, it has also increased relapse rates and toxicity issues such as cytokine release syndrome (a condition after some types of immunotherapy, during which cytokines are rapidly released into the blood), delayed engraftment and T-cell reconstitution, mucositis (inflammation of the lining of the digestive system), infections, heart-related events and non-relapse mortality, Srour added.

However, GVHD relapse-free survival rates in this patient population remain low. Through allograft optimization, Orca-Q may improve haploidentical stem cell transplantation.

The trial enrolled patients aged 18 to 65 years with the following high-risk hematologic cancers: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), very high– or high-risk myelodysplastic syndrome or myelofibrosis.

The main goals of the study were to assess side effects that may limit the doses administered to patients and primary graft failure.

Off the 33 patients enrolled onto the study, the median age is 43 years. Their primary disease was ALL (30.3%), AML (63.3%) or chronic myeloid leukemia (6.1%). Additionally, patients had high-/very high­–risk disease (18%) or intermediate-risk disease (79%).

Patients’ disease status at time of transplant encompassed those who achieved their first complete remission (the disappearance of all signs of cancer from treatment; 73%), second complete remission (24%) and CML accelerated phase (when cells grow faster and lead to symptoms like weight loss, fatigue, fever and enlarged spleen; 3%).

Rapid engraftment with Orca-Q was observed in the patients. The median engraftment time with neutrophils (a type of white blood cell) was 12 days and 15.5 days with platelets (pieces of cells that helps blood clot). Two patients experienced secondary graft failure, and mild to moderate cytokine release syndrome occurred in three patients.

Additional data showed a low incidence of moderate (nine patients) and severe or worse (15 patients) infections. There were five events (15%) of acute moderate to life-threatening GVHD and one event of severe acute GVHD. At a median follow-up of 375 days, no patients have developed moderate to severe chronic GVHD. This in comparison to historical cohorts with posttransplant cyclophosphamide, which show one-year chronic GVHD rates of 24% to 33%.

The phase 1 trial is continuing to enroll patients across the United States. Srour stated that there are plans to increase the age criteria to 75 years and provide less-intensive conditioning therapy.

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