Combination Therapy Enhances Stem Cell Mobilization in Patients With Multiple Myeloma

April 16, 2019

A phase III trial evaluated intermediate-dose cytarabine plus granulocyte-colony stimulating factor (G-CSF) vs G-CSF alone prior to autoSCT in multiple myeloma.

Intermediate-dose cytarabine (ID-AraC) in combination with granulocyte-colony stimulating factor (G-CSF) improved stem cell mobilization in patients with multiple myeloma compared with those who received G-CSF alone prior to tandem autologous stem cell transplantation (autoSCT), according to a recent phase III trial published in Biology of Blood and Marrow Transplantation.

The study, conducted by Czerw and colleagues at the Maria Sklodowska-Curie Institute in Poland, aimed to compare the efficacy of chemo-mobilization using ID-AraC plus G-CSF with that of G-CSF alone in patients with multiple myeloma referred for tandem autoSCT. The primary endpoint was the percentage of patients with a stem cell yield of at least 5 × 106 CD34+ cells/kg.

A total of 90 patients were enrolled in the study, 44 to the G-CSF arm and 46 to the ID-AraC arm, between March 2013 and March 2016. The median age of patients in the G-CSF arm was higher (60 years; range, 37–65 years) than in the ID-AraC arm (56 years; range, 33–65 years; P = .04). Patients in the G-CSF arm received 2 x 5 µg/kg filgrastim subcutaneously each day for up to 7 days. Patients in the ID-AraC arm received 0.4 g/m2 of cytarabine as an infusion twice daily every 12 hours on days 1 and 2 and then on day 5, 2 x 5 µg/kg filgrastim was started. Apheresis began when the level of neutrofil recovery from nadir reached at least 10 cells/µL and continued up to 3 days or until the minimum number of CD34+ cells were collected.

For the primary endpoint, 98% and 70% of patients in the ID-AraC arm (43/46) and in the G-CSF arm (32/44), respectively, reached the stem cell yield minimum (P = .0003). The median number of CD34+ cells was 3.4 times higher in the ID-AraC group (20.2 × 106 CD34+ cells/kg than in the G-CSF group (5.9 × 106 CD34+ cells/kg; P < .000001). For 86% of the patients in the ID-AraC arm (37/46) and 41% of those in the G-CSF arm (13/44), a single apheresis sufficed to collect at least 5 × 106 CD34+ cells/kg (P = .00008).

All patients in both groups completed the mobilization stage; however, hospitalization time was shorter in the G-CSF group (9 days; range, 5–15 days) compared with the ID-AraC group (16 days; range, 14–21 days; P = .000001). Patients in the ID-AraC group experienced grade 3 (9%) and 4 (25%) neutropenia and grade 3 (27%) and 4 (48%) thrombocytopenia, whereas those in the G-CSF group did not. While no bleeding episodes occurred, 34% of patients in the ID-AraC group required platelet transfusion compared with only 2% of patients in the G-CSF group.

“ID-AraC is not typically used in most countries to harvest cells from patients with myeloma,” said Amit Patel, PhD, of the Clatterbridge Cancer Centre NHS Foundation Trust and University of Liverpool, in an interview with Cancer Network. “The yield was better with chemotherapy, but 4 million cells per kg is sufficient for two transplants, so the higher yield may not be clinically meaningful.”

While ID-AraC showed an advantage over G-CSF in terms of stem cell mobilization, additional studies are needed to establish how it compares head-to-head with other more common mobilization regimens, such as cyclophosphamide combined with G-CSF. Furthermore, it remains unknown whether, after transplantation, the increased number of cells will translate into improved long-term outcomes for these patients.