A comparison of CD34+ mobilization effects of standard dose pegfilgrastim (Peg) versus low-dose peg combined with plinabulin (Plin).
e20000 Background: Plin is a novel, small molecule immune-enhancing agent with in vitro anticancer activity currently in Phase (Ph) 3 clinical trials for NSCLC treatment and Chemotherapy (Chemo)-Induced Neutropenia (CIN). Single agent (SA) Plin is equally effective as Peg for the prevention of CIN, however does not cause bone pain and is given on the same day of Chemo by 30 min IV infusion, 30 min after Chemo (Blayney ASH 2018). SA Plin also mobilizes CD34+ cells to clinically relevant levels (Blayney ASH 2019). Plin has been administered to > 600 patients (pts) and has a favorable safety/tolerability profile. In clinical practice, Peg dose is often reduced to 3 mg in patients (pts) experiencing side effects with standard dose (6 mg) Peg, such as bone pain, myalgia and leucocytosis (Kim ASCO 2010; Goodman Oncology Times 2008; Lacovelli JHOP 2012; Lower Cancer Chemother Pharmacol 2018). We evaluated CD34+ cell counts and adverse events (AE) with low dose Peg combined with Plin vs full dose Peg. Methods: In a subset of Breast Cancer pts in the CIN Ph 2 trial BPI-2358-106 (NCT0329457) receiving TAC (taxotere (75), doxorubicin (50 ) and cyclophosphamide (500) mg/m2, pts also received either Peg 6mg (n = 7) or low dose peg ( n = 9, of which 7pts received 3mg and 2 pts 1.5 mg Peg) combined with Plin (20 mg/m2). CD34+ counts were obtained by central laboratory FACS analysis (Covance) at screening (SC), Day (D) 6,8 and 21 cycle 1 (see table below) and AE frequency was collected. Results: Clinical trial information: NCT0329457 . Frequency of bone pain, myalgia and leukocytosis was numerically lower with low dose Peg/Plin vs 6mg Peg. Conclusions: Under highly myelosuppressive TAC Chemo conditions, CD34+ counts increased significantly (p < 0.03) vs predose SC in cycle 1 in the low dose Peg/Plin goup. CD34+ counts were not different for full dose Peg vs low dose Peg/Plin in cycle 1. Adverse Events were fewer with the low dose Peg/Plin. The Peg/Plin combination is worthy of test in hematopoietic stem cell mobilization regimens. [Table: see text]