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New Data Shows Addition of BeyondSpring’s Plinabulin Reverses Neulasta’s Potential Immune-Suppressive Phenotype in Treating Chemotherapy-Induced Neutropenia
Neulasta, a long-acting G-CSF and the current standard of care for CIN, is believed to activate the bone marrow, resulting in an overproduction of neutrophils, many of which are immature. Immature neutrophils can make their way to the tumor tissue and make the microenvironment immune-suppressive. Established markers for immune-suppression are high Neutrophil-to Lymphocyte Ratio (NLR>5) and low Monocyte-to-Lymphocyte Ratio (MLR<3.2), which are associated with low survival outcomes in cancer patients. Previously,
In its Study 106 (using TAC, or Taxotere, Doxorubicin and Cyclophosphamide, as an example of high-risk chemotherapy),
The Plinabulin and Neulasta combination data shows better efficacy for the treatment of CIN, versus Neulasta alone, while preventing neutrophil overproduction. The percentage of patients with grade 4 neutropenia was lowered from 59 percent with Neulasta alone to 38 percent with the combination, and the percentage of patients with an absolute neutrophil count (ANC) exceeding the upper limit of what is considered normal was lowered from 50 percent with Neulasta alone to 31 percent with Neulasta and Plinabulin. Additionally, immune-suppressive NLR levels were lower (<25 percent of patients) in the Plinabulin / Neulasta combination, versus Neulasta alone (>50 percent of patients; p<0.0007 in the cycle). The MLR data showed a similar trend as well.
“These new results from our poster presentation at this year’s ASCO-SITC Symposium, which marks BeyondSpring’s first abstract for Phase 2 of Study 106, provide additional rationale for developing Plinabulin in combination with Neulasta,” said Dr. Blayney. “This combination provides immense clinical benefit and reinforces earlier data from our studies with Plinabulin.”
“The cancer treatment landscape is increasingly moving toward immunotherapy / chemotherapy combinations that also cause CIN,” added Dr.
About Chemotherapy-Induced Neutropenia
As many as 90 percent of patients on high-risk chemotherapy and G-CSF monotherapy may still experience grade 3 or 4 neutropenia (Lee et al., Annals of Surgical treatment and research 94(5): 223-228 (2018)). Patients with grade 4 (severe) neutropenia have an abnormally low concentration of neutrophils, making these patients more susceptible to bacterial and fungal infections and sepsis, which can require hospitalization and be fatal. Grade 4 CIN can have an adverse effect on chemotherapy administration and is usually considered a significant predictor of low relative dose intensity (RDI), dose delays and dose reductions (Lalami Y, Critical Reviews in Oncology / Hematology, 120: 163 – 179 (2017)). A reduction in dose of as little as 15 percent can reduce long-term survival by as much as 50 percent (Bonadonna, Med Oncol 29:1495–1501 (2012)).
As many as 70 percent of patients using G-CSF monotherapy experience bone pain while on G-CSF monotherapy (Moore et al., Annals of Pharmacotherapy 51(9): 797-803 (2017)). Additionally, 25 percent of patients report that the pain is severe. NCCN guidelines require that patients with grade 3/4 neutropenia decrease chemotherapy dose intensity, delay chemotherapy cycle timing or discontinue chemotherapy, each of which can have a negative effect on the long-term outcomes of cancer care (Lalami et al., Critical Reviews in Oncology / Hematology 120: 163-179 (2017)).
Cautionary Note Regarding Forward-Looking Statements
Neulasta® is a registered trademark of Amgen, Inc.