Anti-Monocyte + Granulocyte monoclonal antibody, clone 86-34-27

Importance Plinabulin is a novel, non-granulocyte colony-stimulating factor (GCSF) small molecule with both anticancer and neutropenia-prevention effects. Objective To assess the efficacy and safety of plinabulin compared with pegfilgrastim for the prevention of chemotherapy-induced neutropenia following docetaxel chemotherapy in patients with non-small lung cancer. Design, Setting, and Participants This was a randomized, open-label, phase 2 clinical trial of 4 treatment arms that was conducted in 19 cancer treatment centers in the United States, China, Russia, and Ukraine. Participants were adult patients with non-small cell lung cancer whose cancer had progressed after platinum-based chemotherapy. Data were collected from April 2017 through March 2018 and analyzed from August 2019 through February 2020. Interventions All patients received docetaxel 75 mg/m(2)on day 1 and were randomly assigned to 1 of 3 doses of plinabulin (5, 10, or 20 mg/m(2)) on day 1 or to pegfilgrastim 6 mg on day 2. Patients were treated every 21 days for 4 chemotherapy cycles. Main Outcomes and Measures The primary end point was the determination of the recommended phase 3 dose of plinabulin based on the days of severe neutropenia during chemotherapy cycle 1. Daily complete blood cell counts and absolute neutrophil counts were drawn during times of anticipated neutropenia during cycle 1. Results Of the 55 patients randomized and evaluated, the mean (SD) age was 61.3 (10.2) years, and 38 (69.1%) were men. With each escalation of the plinabulin dose, the incidence of any grade of neutropenia decreased. There were no significant differences in mean (SD) days of severe neutropenia among those treated with pegfilgrastim (0.15 [0.38] days) when dosed at day 2 vs plinabulin 20 mg/m(2)(0.36 [0.93] days;P = .76) when dosed at day 1, and no safety signals were detected. Conclusions and Relevance Single dose-per-cycle plinabulin has a similar neutropenia protection benefit as pegfilgrastim. Plinabulin 40 mg fixed dose, which is pharmacologically equivalent to 20 mg/m(2), will be compared with pegfilgrastim 6 mg in the phase 3 portion of this trial. Noninferior days of severe neutropenia will be the primary end point, and bone pain reduction, thrombocytopenia reduction, and quality of life maintenance will be secondary end points.

Severe neutropenia is defined as an absolute neutrophil count (ANC) of less than 0.5 x 10(9)/L. Severe congenital neutropenia (SCN) is an inborn disorder with maturation arrest of granulocytes due to various genetic abnormalities, which may lead to immunodeficiency. Among several associated genetic mutations, the variants or heterozygous mutations of the ELANE gene coding neutrophil elastase comprise approximately 50% of the genetic causes of SCN. We present a newborn (male) with severe neutropenia due to a novel ELANE gene mutation. The newborn was born at 38(6/7)weeks gestation to a 25-year-old mother with hypertension and morbid obesity. Pregnancy and delivery were uncomplicated but the baby obtained a complete blood count (CBC) on day of life 2 for a work up of hyperbilirubinemia. He was noted to initially have an ANC of 0.2 x 10(9)/L and 0 on subsequent blood counts. A bone marrow biopsy showed a left shift and consistent with myeloid maturation arrest. In direct DNA sequencing analysis, we found an ELANE gene mutation (Val119Glu, V119E), which may be a new gene mutation to cause SCN. The diagnosis of SCN in newborns is usually based on neutropenia identified on a routine CBC. Sufficient awareness and high suspicion of this rare disease can prevent missed or delayed diagnosis of SCN. Our analysis also suggests a new pathological mutation in the ELANE gene and supports the important role of molecular testing in SCN.