A phase II trial with the combination of plinabulin (plin) pegfilgrastim (peg): Evaluation of the reversal of peg’s immune-suppressive potential by the addition of plin to peg.

Abstract

4 Background: Peg is a long-acting G-CSF used for prevention of Chemotherapy Induced Neutropenia (CIN). Peg stimulates granulopoiesis in bone marrow and causes a temporary overshoot in absolute neutrophil count (ANC). High NLR is a negative prognostic marker in esophageal, renal cancer and melanoma (Zhou, Nature 2016; Ma, Nature 2018). Decreased Lymphocyte-to Monocyte Ratio (LMR) is another negative prognostic marker (Sierzega; Ann Surg Onc 2017). Peg single agent (SA), but not Plin SA, increased NLR, and decreased LMR (Blayney ESMO 2018) after Docetaxel (Doc). We analyzed whether Plin added to Peg would reverse Peg’s immune-suppressive potential by analyzing NLR and LMR with Peg SA and with Plin+Peg. Methods: NLR and LMR were calculated in cycle 1 of Ph2 study BPI-2358-106 with either Peg SA (6 mg; n = 22), Plin SA (20 mg/m2; n = 15) or Peg 6 mg and Plin 20 mg/m2 (Peg+Plin; n = 21). NLR and LMR were calculated after day (D) 8, since Peg increases leukocytes after D8, and were performed through D15. Plin was given D1 of chemotherapy (Doc, Doxorubicin, Cyclophosphamide) in Breast Cancer patients (pts); Peg was given D2. Results: The percentage (%) of pts with grade 4 neutropenia was lowered from 59% with Peg SA to 38% by adding Plin to Peg. The % of pts with an ANC exceeding upper limit of normal (8x10E9/L) was lowered from 50% with Peg SA to 31%, by adding Plin to Peg. The table summarizes the % of patients with NLR ≥ 5 and LMR ≤3.2 over time with Peg SA, Plin SA and Peg+Plin. Peg-induced immune-suppressive NLR and or LMR levels occurred in 50% or more of pts, and in a significantly lower % of pts by adding Plin to Peg (p < 0.0076 for NLR and p < 0.073 for LMR on D13). Conclusions: Peg, but not Plin generates a potentially deleterious NLR and LMR which was significantly reversed by the addition of Plin to Peg. The Peg+Plin combination improves efficacy for CIN and reversed Peg’s potentially immune-suppressive NLR and MLR phenotype. Clinical trial information: NCT03294577. [Table: see text]