In a phase II trial reported in the Journal of Clinical Oncology, Desai et al found that the addition of the myeloid progenitor cell product romyelocel-L to granulocyte colony-stimulating factor (G-CSF) reduced the incidence of infection and antimicrobial use vs G-CSF alone during induction chemotherapy in acute myeloid leukemia (AML).
Romyelocel-L (CLT-008) is a cryopreserved, universal, human allogeneic myeloid progenitor cell product manufactured via ex vivo expansion of CD34 hematopoietic stem cells. Infusion of the agent results in production of neutrophils, which may reduce the risk of infection associated with chemotherapy-induced neutropenia.
Study Details
In the U.S. multicenter trial, 120 evaluable patients with de novo AML enrolled between 2015 and 2017 were randomly assigned on the first day of induction chemotherapy (day 0) to receive a single infusion of romyelocel-L (7.5 × 106 cells/kg) within a 3-day period from days 9 to 11 plus G-CSF (n = 59) or G-CSF alone (n = 61). G-CSF was given once daily starting on day 14 and was continued until neutrophil recovery, defined as ≥ 1 absolute neutrophil count (ANC) of ≥ 500/mL. The anticipated onset of biologic activity of romyelocel-L is at approximately 6 days after infusion Outcome measures included days in febrile episode, infections, and days in the hospital.
Key Findings
From days 9 to 28, the mean days in febrile episode were 6.46 in the romyelocel-L group vs 6.86 in the control group (P = .35). From days 15 to 28, the mean days were 2.36 vs 3.90 (P = .02), consistent with the timing of the onset of biologic activity of romyelocel-L.
The combined incidence of microbiologically defined and clinically diagnosed infection was 35.6% in the romyelocel-L group vs 47.5% in the control group (P = .09) from days 9 to 28, with a significant reduction (6.8% vs 27.9%, P = .002) from days 15 to 28. Reductions in both microbiologically defined (3.4% vs 11.5%, P = .05) and clinically diagnosed infections (3.4% vs 16.4%, P = .01) were observed from days 15 to 28.
From days 9 to 28, 44.1% vs 63.9% of patients received antibacterial or antifungal agents for treatment of infection (P = .01). Empiric antifungal treatment was received by 42.4% vs 63.9% (P = .02) from days 9 to 28 and 42.4% vs 62.3% (P =.02) from days 15 to 28.
The total number of hospital days was 25.5 vs 28.7 (P = .002).
ANC recovery from days 0 to 42 was observed in 80.0% vs 84.5% of patients, with a median time to recovery of 21 days in both groups (P = .48).
Serious adverse events occurred in 12.9% vs 18.3% of patients. Romyelocel-L infusion reactions occurred in six patients (all grade 1). No graft-vs-host disease was observed. Death due to infection occurred in two patients in the control group and none in the romyelocel-L group.
The investigators concluded: “Subjects receiving romyelocel-L showed a decreased incidence of infections, antimicrobial use, and hospitalization, suggesting that romyelocel-L may provide a new option to reduce infections in patients with AML undergoing induction therapy.”
Pinkal M. Desai, MD, MPH, of Weill Cornell Medical College, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by a contract with the U.S. Department of Health and Human Services. For full disclosures of the study authors, visit ascopubs.org.
