P-162: Adding Plinabulin to pegfilgrastim to shorten neutropenia and improve quality of life peri-autologous hematopoietic cell transplant for multiple myeloma

Introduction: High dose melphalan with autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma is effective for disease control, but has a period of obligate neutropenia. With a mechanism of action distinct to G-CSF, plinabulin, a selective immunomodulating microtubule-binding agent, prevents chemotherapy-induced neutropenia (CIN) and may have anti-tumor activity in solid tumors. In this pilot study (NCT05130827), plinabulin was incorporated with the intent to shorten the duration of neutropenia after AHCT, thereby limiting the toxicities at count nadir.

Methods: On Day 0, 40mg of intravenous plinabulin was given 1-3 hours after stem cell infusion with pegfilgrastim on Day +1. Plinabulin pharmacokinetic profiling (end of infusion, 30min, 4hr, 24hr, and 48hr), toxicities of the combination, engraftment, disease response, progression free and overall survival, and patient reported outcome (PRO) assessment of symptom burden were secondary endpoints. Eleven concurrent standard-of-care (SOC) patients had similar assessments for comparison.

Results: Between January 2022 and February 2023, 15 patients (median age 64 (range 54-74), 67% female, 73% melphalan 200mg/m2) received plinabulin. Median CD34+ cells/kg infused was 4.12 x 10^6 (range 2.18 – 7.85). Half the patients had hypertension (HTN) immediately after the plinabulin infusion, which is a known toxicity and resolved within a few hours. Median plinabulin serum AUC was 1249.5mg*h/L (range 192.6 -5092.5). Median WBC on Day 0, 1, and 2 was 7.67 (3.6 – 11.5), 5.2 (3.2 – 13.6), and 17.1 (5.1-59.1), respectively. Median time to ANC >0.5 x 10^9 cell/L was 11 days (range 8-16) with median days from AHCT to ANC < 0.5 of 5 days (range 5-6). Median number of days of ANC < 0.1 and < 0.5 were 2 (range 1-5) and 5 days (range 3-9), respectively. Median time to fever was 8 days from AHCT (n = 8, range 7-12), and all except one were attributed to engraftment syndrome. Median length of stay was 18 days (range 15-21). Median pRBC and platelet transfusions were 0 (range 0-3) and 2 (range 0-11), respectively. For the SOC patients, engraftment timing was similar, but 2 had HTN, 3/7 with fever had non-engraftment neutropenic fevers (NENF), and median pRBC and platelet transfusions were 1 (range 0-8) and 4 (range 1-14), respectively.

Conclusions: The addition of plinabulin to pegfilgrastim did not add major toxicities after AHCT. Patients had elevated WBC on Day +2, low rates of NENF, and potentially less need for transfusion support. Plinabulin PK, quality of life data, and PROs will be presented. Adjusting the schedule of plinabulin to Day 3 may allow stem cells to reach the bone marrow niche prior exposure to plinabulin and thereby use the novel mechanism of action to shorten the duration of neutropenia.