Effective Primary Mobilization of Autologous Peripheral Blood Stem Cells with Granulocyte Colony-Stimulating Factor and Plerixafor in Lenalidomide-Treated Patients with Multiple Myeloma

Lenalidomide (LEN) is extensively used in combination with dexamethasone (DEX), with or without bortezomib (BOR), for initial treatment of multiple myeloma (MM). However, several studies have shown that previous exposure to LEN is associated with impaired collection of autologous peripheral blood stem cells (PBSCs) after mobilization with either granulocyte-colony stimulating factor (G-CSF) or chemotherapy plus G-CSF. The effects of previous exposure to LEN on the collection of autologous PBSCs after mobilization with G-CSF plus plerixafor (PLX; Mozobil®) are not well described.

We evaluated the outcomes of autologous PBSC mobilization and collection in 15 consecutive patients (pts) with MM who received previous treatment with at least 2 21-day cycles of LEN in combination with either DEX (10 pts) or DEX and BOR (5 pts) and who underwent initial autologous PBSC mobilization with G-CSF (10 micrograms/kg/dose subcutaneously daily × 4 days) and PLX (0.24 mg/kg/dose subcutaneously, after fourth dose of G-CSF), with additional doses of G-CSF and PLX for subsequent apheresis sessions.

Median age of pts was 58 yr (range, 35–67). Patients received a median of 5 cycles (range, 2–12) of LEN. The median number of apheresis sessions was 1 (range, 1–2). The median level of CD34+ cells in the peripheral blood at day 1 of apheresis was 84.36 per microliter (range, 12.46–167.37), and the median yield of CD34+ cells was 6.52 × 10⁶/kg (range, 1.43–17.11) after day 1 of apheresis and 7.46 × 10⁶/kg (range, 2.32–17.11) after day 2 of apheresis. No LEN-treated pts failed mobilization (defined as collection of less than 2 × 10⁶ CD34+ cells/kg). Eleven pts (73.3%) collected at least 6 × 10⁶/kg CD34+ cells (i.e., sufficient for 2 transplants) after 1 or 2 aphereses, with 8 pts (53.3%) reaching that target after 1 apheresis. Of the 4 pts (26.7%) in whom fewer than 6 × 10⁶/kg CD34+ cells were collected after 2 aphereses, 3 pts collected at least 4 × 10⁶ CD34+ cells/kg, and only 1 pt (who received only 2 cycles of LEN) collected 2.32 × 10⁶/kg CD34+ cells. The number of cycles of LEN did not correlate with concentration of CD34+ cells in peripheral blood on day 1 of apheresis (r²=0.099), yield of CD34+ cells on day 1 of apheresis (r²=0.108), or total yield of CD34+ cells after 2 days of apheresis (r²=0.067). Pts who received 4 or fewer cycles of LEN had higher median circulating CD34+ cells on apheresis day 1, higher median CD34+ cell yield with day 1 apheresis and higher total CD34+ cell yield after 2 aphereses than pts who received more than 4 cycles of LEN (Table). Five of 6 pts who received 4 or fewer cycles of LEN collected at least 6 × 10⁶ CD34+ cells/kg after 1 apheresis, compared with 3 of 9 pts who received more than 4 cycles. However, none of these differences were statistically significant (Table).

Previous treatment with LEN does not impair collection of autologous PBSCs after initial mobilization with G-CSF and PLX. However, there was a trend to more robust autologous PBSC collections and decreased need for second aphereses in pts who received fewer cycles of LEN. These findings are consistent with the recommendation of the International Myeloma Working Group to collect autologous PBSCs from MM pts after 4 or fewer cycles of LEN-containing regimens. As mobilization with G-CSF with or without chemotherapy leads to inconsistent autologous PBSC collection in LEN-treated MM pts, our experience supports the use of G-CSF plus PLX as an upfront mobilization strategy for these pts.

No relevant conflicts of interest to declare.