Posted: Tuesday, February 16, 2021
At the 2021 Transplantation & Cellular Therapy Meetings (TCT), Lori Muffly, MD, of the Stanford University School of Medicine, California, and colleagues presented their study data on JSP191, a first-in-class monoclonal antibody that targets and depletes hematopoietic stem cells initiating acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Their results concluded that JSP191, in conjunction with low-dose irradiation and fludarabine, is well tolerated and effective in clearing measurable residual disease in patients undergoing nonmyeloablative allogeneic hematopoietic cell transplantation (Abstract LBA5).
“JSP191 acts by inhibiting stem cell factor binding to CD117 present on hematopoietic stem cells,” the investigators stated. “We and others showed in preclinical models that hematopoietic stem cell depletion can be enhanced by combining [an] anti-CD117 monoclonal antibody with low-dose total-body radiation.”
The investigators analyzed three patients with AML or MDS who were 60 years or older. Patients had measurable residual disease detected by next-generation sequencing, cytogenetics, or difference from normal flow cytometry. Participants were administered 0.6 mg/kg of JSP191 intravenously, 30 mg/m2 daily of fludarabine for 3 days, and total-body radiation of 200 cGy on the day of transplantation.
On the day of transplantation, which was 10 to 13 days after JSP191 infusion, cryopreserved peripheral blood grafts from matched donors were administered to each patient. Graft-versus-host disease prophylaxis included sirolimus, mycophenolate mofetil, and tacrolimus. Between 22 and 26 days after transplant, all subjects underwent engraftment with neutrophil recovery. By day 28 after transplantation, all individuals achieved complete donor CD15 myeloid chimerism in the peripheral blood. Additionally, on day 28 after transplantation, all patients demonstrated a reduction in or elimination of measurable residual disease.
Disclosure: For full disclosures of the study authors, visit tct.confex.com.