Evaluation of Romyelocel-L Myeloid Progenitor Cells to Decrease Infections in De Novo AML Patients Receiving High-Dose Ara-C-Based Induction Therapy

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.1407-1407
• Main Authors: Ravandi, Farhad, Abboud, Camille N, Akard, Luke Paul, Gill, Saar I., Hsu, Jack W., Kambhampati, Suman, Khan, Irum, Liu, Delong, Stock, Wendy, Brown, Janice W, Bashey, Asad, Borthakur, Gautam, DiNardo, Courtney D., Holland, H. Kent, Kadia, Tapan M., Kantarjian, Hagop M., Morris, Lawrence E, Solomon, Scott R, Mamelok, Richard David, Panuganti, Swapna, Van Syoc, Rod, Wong, Alicia, Zimmerman, Deborah, Solh, Melhem
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-117231

Background: Induction chemotherapy (7+3) or high-dose ara-C-based (HIDAC) for AML results in prolonged neutropenia with a high risk of serious infection and attendant morbidity, and prolonged hospitalization. Romyelocel-L is a human off-the-shelf allogeneic myeloid progenitor cell (MPC) preparation manufactured by ex vivo culture expansion of CD34+ cells. Following infusion, MPCs are expected to home to bone marrow (BM) and produce neutrophils. In a randomized, open-label, controlled Phase 2 trial, the effect of romyelocel-L was studied in de novo patients receiving HIDAC or 7+3 induction therapy for reduction of fever and infection. The results from pooled and 7+3 cohorts, were previously presented, showing decrease in infections and days in hospital. The results from cohorts receiving HIDAC chemotherapy are presented here. Methods: 53 subjects with de novo AML (age ≥55) and receiving HIDAC induction were randomized on Day 0 (first day of induction) to receive either romyelocel-L (7.5x106 cells/kg) on Day 9 + GCSF qd starting on Day 14 (treatment) or GCSF alone starting on Day 14 (control) qd until ANC recovery to 500/µL. Of the 53 subjects, 42 were considered evaluable (20 in treatment and 22 in control) which meant that they received romyelocel-L + GCSF or GCSF alone, were in study ≥ 28 days and did not receive additional chemotherapy before Day 28. Subjects routinely received corticosteroids concurrently with HIDAC induction. Most patients received prophylactic antibacterial (74%) and antifungal (86%) agents. Endpoints assessed from Day 9 to Day 28 included days in a Febrile Episode (DFE, primary endpoint) and microbiologically defined bacterial or fungal infections (MDI, defined as an infection when a specific pathogen is identified)/clinically diagnosed infections (CDI, defined when there is supporting clinical, laboratory, and/or radiologic data that is sufficient to indicate an infection and no specific pathogen is identified). MDIs and CDIs were adjudicated by a blinded independent committee. The number of days in hospital was assessed through Day 42. Data are reported for 2 periods: from infusion of romyelocel-L (Day 9-28) and from 6 days after infusion of romyelocel-L (1 day after start of GCSF) - Day 28 (denoted as Day 15-28; the period when romyelocel-L derived neutrophils are likely to be circulating.). One-sided p-values are reported. Results: The baseline characteristics, including median age, mean WBC, and ECOG status were balanced between