The risk of infection during induction chemotherapy decreased among patients with acute myeloid leukemia treated with romyelocel-L.
Romyelocel-L helped to lower the incidence of infections, antimicrobial use, and hospitalization in a population of patients with acute myeloid leukemia (AML) who are undergoing induction chemotherapy, according to the results of a phase 2 study (NCT02282215) published in the Journal of Clinical Oncology.
From day 9 to day 28, the mean number of days in febrile episodes was not significantly decreased in the treatment group (6.46 vs 6.86; P = .35). Additionally, no significant decrease in the number of patients who developed febrile neutropenia was identified in either treatment arm. However, significantly fewer days of febrile episodes were observed in the treatment arm from day 15 to day 28 (2.36 vs 3.90; P = .02). There was also a trend towards less microbiologically defined infections and clinically diagnosed infection from day 9 to day 28 in the treatment arm (35.6% vs 47.5%; P = .09); the difference reached statistical significance on day 9 to day 28 (35.6% vs 47.5%; P = .09). This translated to a decrease in use of antibacterial or antifungal treatments for infection within the treatment cohort within that period (44.1% vs 63.9%; P = .01).
Additionally, patients in the treatment arm were in the hospital for 3.2 days less than the control group (25.5 vs 28.7; P = .001). Remission rates and days to absolute neutrophil count recovery were comparable across both groups.
“Infectious complications associated with neutropenia remains the leading cause of morbidity and mortality after AML induction chemotherapy despite an expanded antimicrobial armamentarium. Romyelocel-L was designed to reduce the morbidity and mortality from infections during neutropenia after myeloablative chemotherapy in AML,” the study authors wrote.
To be eligible for the trial, patients needed to be aged 55 years or older with de novo AML and be scheduled to undergo induction chemotherapy. Additionally, an ECOG performance status of 0 to 2 was required, as well as adequate pulmonary, liver, and renal function. The chemotherapy regimen needed to be either 7 plus 3 or a high-dose cytarabine-based combination, including 4 g/m2 or more of cytarabine plus other agents such as purine analogues, anthracyclines, or etoposides. Patients were stratified based on chemotherapy regimen, age, and white blood cell count at the time of screening.
Those who enrolled on the study were randomized 1:1 to receive either a single infusion of romyelocel-L plus granulocyte colony-stimulating factor (G-CSF) or G-CSF alone. Romyelocel-L was administered at a dose of 7.5 x 106 cells/kg within 3 days of day 9 to 11. G-CSF was given once daily starting on day 14 in both cohorts of patients; treatment continued until neutrophil recovery.
The primary end point of the study was mean duration of febrile episode from day 9 to day 28. Key secondary end points included microbiologically documented infections, incidence of clinically documented infections, neutrophil recovery to 500/µL, days of hospitalization from day 0, and platelet reactive antibody measurements.
A total of 163 patients were enrolled throughout 2015 to 2017 from 21 centers in the United States, 120 of whom were evaluable. Fifty-nine and 61 patients from the treatment and control arms were evaluable for response, respectively.
Additional findings from the study indicated that from day 0 to day 42, 50.8% of patients in the treatment arm and 59.0% of patients in the control arm developed clinically documented infections and microbiologically documented infections. During the time from day 21 to day 42, 1 patient in the romyelocel-L plus G-CSF arm and 12 patients in the G-CSF along arm developed a nonminor bacterial or fungal infection. Both the incidence and timings of clinically documented infections and microbiologically documented infections relative to the agents used in the study were notable and consistent with the treatment effects of biologic agents.
“These results provide the foundation for a phase III trial with the primary end point of reduction in infections during intensive induction chemotherapy for adults with AML. Romyelocel-L has great potential not only in reducing infections during induction chemotherapy in AML but also reducing antibiotic resistance, which remains one of the biggest concerns in infection control in immunocompromised patients,” the investigators concluded.
Desai PM, Brown J, Gill S, et al. Open-label phase II prospective, randomized, controlled study of Romyelocel-L myeloid progenitor cells to reduce infection during induction chemotherapy for acute myeloid leukemia. J Clin Oncol. Published online June 22, 2021. doi:10.1200/JCO.20.01739