Plinabulin (Plin) combined with half-dose pegfilgrastim (Peg) compared with full-dose peg alone for chemotherapy- induced-neutropenia (CIN): Neutrophil, bone pain, and immunosuppressive effects.

Abstract

e12017 Background: Peg is used for CIN prevention. Plin, a novel, non-G-CSF agent is in Phase (Ph) 3 trials for CIN prevention and as an anticancer (NSCLC) agent. In contrast to Peg, Plin does not cause bone pain and maintains absolute neutrophil counts (ANC) within the normal range. Furthermore, Peg, but not Plin, increases Neutrophil-to-Lymphocyte Ratio (NLR) and Lymphocyte-to-Monocyte Ratio (LMR) to immune suppressive values; i.e. NLR>5 and LMR<3.2 (Blayney, ASCO 2018, ESMO 2018, ASCO-SITC 2018). We tested the effects on CIN, bone pain and immune-suppressive profile (i.e. NLR> 5 and LMR<3.2), comparing Plin+half Peg dose to full dose Peg alone (the current CIN standard of care). Methods: Early stage Breast Cancer patients (pts) received high febrile neutropenia (FN) risk TAC (docetaxel, doxorubicin, cyclophosphamide) and either full dose Peg 6 mg (Peg6; n=22) or Peg 3 mg (half dose) + Plin 20 mg/m2 (Peg3/Plin; n = 21) in a Ph 2 trial (NCT03294577). Peg was given ~24 hrs after TAC, and Plin ~30 min after TAC. Blood was drawn for ANC, NLR, MLR daily on Day (D) 0 to D15 in cycle 1. Validated bone pain assessments were done at predose D1, 2,3,4,6,7 and 8 in cycle 1. NLR and LMR were calculated from D6 on (ANC effects with Peg or Plin occur after D6). Results: Grade 4 and Grade 3/4 Neutropenia occurred in 59.1% and 81.2% of pts in the Peg6 arm vs 52.4% and 57.1% in the Peg3/Plin arm. Peg3/Plin was well-tolerated and non-inferior to Peg6 for duration of severe neutropenia (P<0.05). FN occurred in 1 pt each in Peg6 and Peg3/Plin. Bone pain with Peg3/Plin was less vs Peg6: frequency of pts with at least 1,3 or 5 days of bone pain was 90.9%, 36.7% and 18.2 % with Peg6, whereas 33.3%, 14.3% and 4.76% with Peg3/Plin (p<0.0001 for at least 1 day). Frequency of NLR≥5 and LMR≤3.2 was higher with Peg6 vs Peg3/Plin (p<0.045 to P<0.0004 between D8 to D15). Clinical trial information: NCT03294577. Conclusions: Half dose Peg combined with Plin is equally effective against CIN as full dose Peg, but with much less bone pain and immune-suppressive potential.[Table: see text]