72171-0501-XX Gamifant 10 mg/2 mL SOLN (Novimmune SA)
72171-0501-XX Gamifant 10 mg/2 mL SOLN (Novimmune SA)
Emapalumab-lzsg is an interferon gamma (IFNγ) blocking monoclonal antibody that binds to and neutralizes interferon gamma (IFNγ). Nonclinical data suggest that IFNγ plays a pivotal role in the pathogenesis of hemophagocytic lymphohistiocytosis (HLH) by being hypersecreted. Emapalumab-lzsg reduces the plasma concentrations of CXCL9, a chemokine induced by IFNγ. Emapalumab-lzsg is produced in Chinese Hamster Ovary cells by recombinant DNA technology.
Emapalumab-lzsg for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Emapalumab-lzsg for the treatment of other conditions/diseases is considered investigational.
Emapalumab-lzsg is considered medically appropriate if ALL of the following:
Individual has been evaluated and screened for the presence of latent TB infection prior to initiating treatment
Individual will receive prophylaxis for Herpes Zoster, Pneumocystis Jirovecii, and fungal infections
Individual does not have an active infection, including clinically important localized infections that are favored by interferon-gamma (e.g., infections caused by mycobacterium, histoplasma, etc)
Must not be administered concurrently with live vaccines
Individual has a definitive diagnosis of Hemophagocytic lymphohistiocytosis (HLH) as indicated by ANY ONE of the following:
Individual diagnosis of primary HLH based on identification of biallelic pathogenic gene variants from molecular genetic testing (e.g., PRF1, UNC13D, STX11, or STXBP2) or a family history consistent with primary HLH
Individual has at least FIVE of the following eight documented criteria:
Prolonged fever (> 7 days)
Cytopenias affecting 2 of 3 lineages in the peripheral blood (hemoglobin < 9 g/dL , platelets <100 x 109/L, neutrophils <1 x 109/L
Hypertriglyceridemia (fasting triglycerides >3 mmol/L or ≥265 mg/dL) and/or hypofibrinogenemia (≤1.5 g/L)
Hemophagocytosis in bone marrow, spleen, or lymph nodes with no evidence of malignancy
Low or absent NK-cell activity
Ferritin ≥ 500 mcg/L
Soluble CD25 (aka soluble IL-2Rα receptor) ≥ 2400 U/mL.
Individual has active, primary disease that is refractory, recurrent, or progressive during, or were intolerant to, conventional HLH therapy (e.g., dexamethasone, etoposide, cyclosporine A, anti-thymocyte globulin, etc.)
Individual has NOT received hematopoietic stem cell transplant (HSCT)*
Used in combination with dexamethasone (patients currently on oral cyclosporine A, or intrathecal methotrexate and/or glucocorticoids may continue on therapy while treated with emapalumab-lzsg)
Emapalumab-lzsg is considered medically appropriate for renewal if ALL of the following criteria are met:
Individual continues to meet initial approval criteria
Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following: serious infections, severe infusion reactions, etc.
Individual is receiving ongoing monitoring for presence of TB or other active infections AND monitoring every 2 weeks for adenovirus, EBV, and CMV viruses and as clinically indicated
Individual continues to require therapy for treatment of HLH
Individual experienced a disease improvement in HLH abnormalities as evidenced by ANY ONE of the following:
Complete response defined as normalization of all HLH abnormalities (i.e., no fever, no splenomegaly, neutrophils > 1x109/L, platelets > 100x109/L, ferritin < 2,000 μg/L, fibrinogen > 1.50 g/L, D-dimer < 500 μg/L, normal CNS symptoms, no worsening of sCD25 > 2-fold baseline)
Partial response defined as normalization of ≥ 3 HLH abnormalities
HLH improvement defined as ≥ 3 HLH abnormalities improved by at least 50% from baseline
Dose escalation requests (up to the maximum dose and frequency specified below) based on clinical and laboratory parameters being interpreted as an unsatisfactory response are defined as at least ONE of the following:
Fever (persistence or recurrence)
If baseline < 50,000/mm3 and no improvement to >50,000/mm3
If baseline > 50,000/mm3 and less than 30% improvement
If baseline > 100,000/mm3 any decrease to < 100,000/mm3
If baseline < 500/mm3 and no improvement to > 500/mm3
If baseline > 500 -1000/mm3 and decrease to < 500/mm3
If baseline 1000-1500/mm3 and decrease to < 1000/ mm3
If baseline ≥ 3000 ng/mL and < 20% decrease
If baseline < 3000 ng/mL and any increase to > 3000 ng/mL
Splenomegaly – any worsening
Coagulopathy (both D-dimer and fibrinogen must apply)
If abnormal at baseline and no improvement
If baseline levels ≤ 100 mg/dL and no improvement
If baseline levels > 100 mg/dL and any decrease to < 100 mg/dL
*Patients should be evaluated for HSCT when a high-risk of relapse and a high-risk of mortality exists (e.g., homozygous or compound heterozygous HLH mutations exists, lack of response to initial HLH therapy, central nervous system involvement, and incurable hematologic malignancy).
DOSAGE & ADMINISTRATION
Administer initial doses of 1 mg/kg, intravenously over one hour, twice weekly. Titrate
doses up to 10 mg/kg as follows:
· On day 3, if an unsatisfactory improvement in clinical condition is assessed by the healthcare provider, increase to 3 mg/kg
· From day 6 through 8, if an unsatisfactory improvement in clinical condition is assessed by the healthcare provider on the 3 mg/kg dose, increase to 6 mg/kg
· From day 9 and onwards, if an unsatisfactory improvement in clinical condition is assessed by the healthcare provider on the 6 mg/kg dose, increase to 10 mg/kg
· Used in combination with dexamethasone at a daily dose of at least 5-10 mg/m2 starting the day before Gamifant treatment begins
· Administer until hematopoietic stem cell transplantation (HSCT) is performed or unacceptable toxicity.
· Discontinue when a patient no longer requires therapy for the treatment of HLH
LENGTH OF AUTHORIZATION
Coverage will be provided for six months and may be renewed.
Refer to DOSAGE LIMITS below
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).
Jordan M, Allen C, Weitzman S, et al. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041. Epub 2011 Aug 9.
Henter, Jan-Inge MD, PhD, Horne, AnnaCarin MD, Arico, Maurizio MD, et al. REVIEW: HLH-2004: Diagnostic and Therapeutic Guidelines for Hemophagocytic Lymphohistiocytosis Pediatric Blood & Cancer 2007;48: 24–131 2006 Wiley-Liss, Inc. DOI 10.1002/pbc
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2018, September). Emapalumab-lzsg. Retrieved December 13, 2018 from MICROMEDEX Healthcare Series.
U. S. Food and Drug Administration. (2018, November). Center for Drug Evaluation and Research. Gamifant™(emapalumab-lzsg) injection, for intravenous use. Retrieved December 13, 2018 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761107s000lbl.pdf
ORIGINAL EFFECTIVE DATE: 4/30/2019
MOST RECENT REVIEW DATE: 4/30/2019
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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Maximum billable units per dose and over time by indication as a Medical Benefit