Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Gastric cancer
Treatment is Neulasta
The insurer denied coverage for Neulasta
The denial is overturned

The patient was diagnosed with signet ring gastric cancer. The patient is status post gastrectomy. The patient is being treated with adjuvant FOLFOX every two weeks for six months. The patient had an absolute neutrophil count (ANC) of 1.76. 

The insurer has denied coverage for Neulasta as not medically necessary. In their Final Adverse Determination letter, they write that the patient has gastric cancer and is receiving a chemotherapy regimen known to cause low white blood cells. However, the records do not show that the patient has a risk factor.

In an appeal email her doctor writes that after chemotherapy cycle (C) #2, the patient developed severe neutropenia (ANC 0.03) on cycle two day (D) one (C2D1). Given the patient's severe neutropenia, C3# FOLFOX was held. The patient was given samples of Zarxio injections; the patient's ANC improved to 8.73 on (C2D22). The patient presented for C3 with a three-week delay.

Neulasta is considered medically necessary for this patient.

Although the patient's ANC of 1.76 did not meet the definition of significant neutropenia, which is ANC 1.5, it was very close. Neutropenia can occur in the subsequent cycles of chemotherapy, and secondary prophylactic treatment would be appropriate. The patient had neutropenia in a previous course of similar chemotherapy and is thus expected to do so again. Subsequent courses hold greater risk than the first one of producing neutropenia. Nuelasta is appropriate and medically necessary.

"INDICATIONS AND USAGE: Neulasta is a leukocyte growth factor indicated to:
- Decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
- Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome)." (Neulasta Package Insert).


Per Brekkan, A., Lopez-Lazaro, L., Plan, E. L., Nyberg, J., Kankanwadi, S., & Karlsson, M. O. (2019), "Neutropenia and febrile neutropenia (FN) are serious side
effects of cytotoxic chemotherapy which may be alleviated with the administration of recombinant granulocyte colony-stimulating factor (GCSF) derivatives, such as pegfilgrastim (PG) which increases absolute neutrophil count (ANC). In this work, a population pharmacokinetic-pharmacodynamic (PKPD) model was developed based on data obtained from healthy volunteers receiving multiple administrations of PG. The developed model was a bidirectional PKPD model, where PG stimulated the proliferation, maturation, and margination of neutrophils and where circulating neutrophils in turn increased the elimination of PG. Simulations from the developed model show disproportionate changes in response with changes in dose. A dose increase of 10% from the 6 mg (milligram) therapeutic dose taken as a reference leads to area under the curve (AUC) increases of ~50 and ~5% for PK (pharmacokinetic) and PD (pharmacodynamic), respectively. A full random effects covariate model showed that little of the parameter variability could be explained by sex, age, body size, and race. As a consequence, little of the secondary parameter variability (Cmax and AUC of PG and ANC) could be explained by these covariates." (Brekken, A., et al. 2018).                                                         

The insurer's denial of coverage for Neulasta is overturned. Medical Necessity is substantiated.