Outpatient HSCT feasible for older adults with AML, myelodysplastic syndrome
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Outpatient hematopoietic stem cell transplantation following targeted antibody-based conditioning appeared safe and feasible among older patients with acute myeloid leukemia or myelodysplastic syndrome, according to study results.
The findings, presented at 2023 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, indicated that outpatient HSCT using the anti-CD117 monoclonal antibody JSP191 with a standard nonmyeloablative conditioning regimen could lead to lower hospital resource use and spare hospitals and patients long-term hospitalizations.
Background and methods
“The issue with our older-adult patients is we tend to use lower-intensity conditioning regimens due to the toxicity of high-intensity chemotherapy or radiation therapy. However, when we dial back the intensity of conditioning, tolerability improves but relapse rates go up after transplant,” Lori Muffly, MD, MS, associate professor of medicine at Stanford University School of Medicine, told Healio. “If we had a way of providing conditioning where the toxicity was low but we could improve upon the efficacy against AML and MDS [myelodysplastic syndrome], that would be really important.”
The subanalysis of the phase 1 trial aimed to assess the safety of a conditioning regimen that consisted of JSP191 (Jasper Therapeutics) at a dose of 0.6 mg/kg via IV, followed by 30 mg/m² fludarabine daily for 3 days and 2 Gy to 3 Gy total body irradiation on transplant day.
Researchers examined clinical outcomes and resource utilization during the first 100 days after transplant among 12 patients (median age, 70 years) with AML in morphologic complete remission (n = 4) or MDS (n = 8) who underwent the JSP191-based conditioning and donor cell infusion in the outpatient setting, with discharge from the hospital on the same day.
Primary endpoints included safety, tolerability of the conditioning regimen and pharmacokinetics.
Median follow-up was 6 months.
Findings
Neutrophil recovery among the 12 engrafted patients occurred between day 15 and day 26 after transplant. At day 100, five patients had experienced nine infections.
Half of the patients required no subsequent hospitalization in the first 100 days after transplant (mean length of stay, 4 days). One patient with AML required hospitalization twice, for enterocolitis and recurrence of diverticulitis. However, researchers observed no serious treatment-associated adverse events.
“We have now treated more than 30 patients since baseline, but for the 12 patients included in this current analysis, we found that this platform of conditioning is safe for those who have reached at least 1-year post-transplant follow-up,” Muffly said. “We observed no infusion reactions with the antibody, no serious adverse events related to the antibody, and all patients experienced full donor engraftment.”
Moreover, clearance of the antibody appeared consistent and predictable across all 12 patients, she continued.
“This is a stem cell-targeting antibody that could theoretically kill off donor stem cells,” Muffly said. “The clearance of the antibody will be very helpful for future studies. Here, we performed real-time pharmacokinetic analysis to evaluate clearance, but we believe that the clearance is so predictable that it would not be needed for future studies or future use of this drug.”
Muffly noted that nine patients had measurable residual disease going into transplant.
“Among the nine patients with MRD-positive disease, six patients had cleared their MRD at 1-year post-transplant and one patient died of transplant-related toxicity,” she said.
Results also showed a 1-year relapse-free survival rate of 67% and 1-year OS of 75%, according to Muffly.
“We are very pleased with these results because this is such an older-adult population with high-risk AML and MDS treated with such a tolerable regimen,” she said.
Implications
Researchers now plan to study JSP191 in a randomized phase 3 trial for the older AML and MDS patient population.
“Future research should also include additional assessment of the antibody in combination with additional conditioning regimens,” Muffly said. “The preclinical work done with this antibody showed synergy with radiation therapy, so prioritizing radiation therapy-based conditioning regimens to explore the antibody with is important in other patient populations. Also, next-phase studies are needed to determine the efficacy of the antibody relative to nonantibody approaches.”
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Muffly L, et al. Abstract 86. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, Feb. 15-19, 2023; Orlando.
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