Subject:
Tagraxofusp-erzs (Elzonris)
Description:
_______________________________________________________________________________________
IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
__________________________________________________________________________________________________________________________
Elzonris (tagraxofusp-erzs) is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid dendritic cell neoplasm in adults and in pediatric patients two years and older.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN), previously known as natural killer cell leukemia and lymphoma, presents with features of both lymphoma and leukemia. BPDCN is often misdiagnosed and under-reported due to the difficulty of diagnosing patients. More men than women are diagnosed with BPDCN and the average age at diagnosis is sixty to seventy years. BPDCN most frequently involves the skin and usually progresses with bone marrow involvement, and potentially the spleen and lymph nodes. There is limited data on this disease state and therefore, the only approved treatment of BPDCN in adult and pediatric patients two years and older is Elzonris (tagraxofusp-erzs). The current recommendation for BPDCN patients is to be evaluated for an allogeneic hematopoietic stem cell transplant and to begin searching for a donor.
Elzonris (tagraxofusp-erzs) is a CD123-directed cytotoxin composed of recombinant human interleukin-3 (IL-3) and truncated diphtheria toxin (DT) fusion protein that inhibits protein synthesis and causes cell death in CD123-expressing cells.
The safety and efficacy of Elzonris (tagraxofusp-erzs) was demonstrated in study 1 through a non-randomized, multicenter, open-label, single-arm, clinical trial that included a prospective cohort of thirteen patients with treatment-naïve BPDCN. Study 2 was a multicenter, open-label, single-arm clinical trial that included fifteen patients with relapsed or refractory BPDCN.
Study inclusion criteria included patients with a diagnosis of acute myeloid leukemia or BPDCN according to the World Health Organization classification. Patients were excluded for many criterions including but not limited to, if they had received chemotherapy, wide-field radiation, or biologic therapy within fourteen days of study entry, if they had received treatment with another investigational drug within fourteen days of study entry, or if the patient was previously received treatment with Elzonris (tagraxofusp-erzs).
Study 1 treatment consisted of Elzonris (tagraxofusp-erzs) 12mcg/kg intravenously over fifteen minutes once daily on days one to five of a twenty-one day cycle. Patient baseline characteristics included 84.6% males and 15.4% females. The median age of patients was 65 years old. The Eastern Cooperative Oncology Group (ECOG) performance score was 0 for 61.5% of patients and 1 for 38.5% of patients. The final characteristic evaluated BPDCN at baseline. BPDCN was present in the skin for 100% of patients, 53.8% of patients had progression to the bone marrow, 23.1% had progression to the peripheral blood, 46.2% had progression to the lymph nodes, and 15.4% had progression to the viscera. The efficacy of Elzonris (tagraxofusp-erzs) in patients with treatment-naïve BPDCN was based on the rate of complete or clinical complete response (CR/CRc), where CRc is defined as complete response with residual skin abnormality not indicative of active disease. Key efficacy measures included the CR/CRc rate, duration of CR/CRc, duration of follow-up. The median time to CR/CRc was 57 days.
Study 2 treatment consisted of Elzonris (tagraxofusp-erzs) 12mcg/kg intravenously on days one to five of a twenty-one day cycle. Patient baseline characteristics included 86.7% males and 13.3% females. The median age of patients was 72 years old. The ECOG performance score was 0 for 33.3% of patients and 1 for 66.7% of patients. The final characteristic evaluated BPDCN at baseline. BPDCN was present in the skin for 86.7% of patients, 60.0% of patients had progression to the bone marrow, 6.7% had progression to the peripheral blood, 53.3% had progression to the lymph nodes, and 26.7% had progression to the viscera. In the patients with relapsed/refractory BPDCN, one patient achieved CR duration of 111 days and one patient achieved CRc duration of 424 days.
[INFORMATIONAL NOTE: BLACK BOX WARNING: Capillary Leak Syndrome: Capillary Leak Syndrome which may be life-threatening or fatal if not properly managed, can occur in patients receiving Elzonris (tagraxofusp-erzs)]
Policy:
(Note: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
1. Elzonris (tagraxofusp-erzs) is medically necessary for the following FDA approved indications when the following criteria are met:
a. Treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older
i. The patient has an ECOG performance score (PS) of 0-2
2. When Elzonris (tagraxofusp-erzs) is medically necessary, initial therapy will be approved for 1 year at the FDA recommended dosage of:
a. 12 mcg/kg intravenously over 15 minutes once daily on days 1 to 5 of a 21-day cycle.
[INFORMATIONAL NOTE: Prior to initiating therapy with Elzonris (tagraxofusp-erzs), ensure the patient has adequate cardiac function and serum albumin is ≥3.2g/dL. Premedicate with an H1-histamine antagonist, acetaminophen, corticosteroid and H2-histamine antagonist prior to each Elzonris (tagraxofusp-erzs) infusion. During treatment with Elzonris (tagraxofusp-erzs), monitor serum albumin levels prior to the initiation of each dose and as indicated clinically thereafter, and assess patients for other signs or symptoms of CLS, including weight gain, new onset or worsening edema, including pulmonary edema, hypotension or hemodynamic instability.
Recommended Elzonris Dose Modifications
Parameter | Severity Criteria | Dose Modification |
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) | ALT or AST increase > 5 times the upper limit of normal | Withhold Elzonris until transaminase elevations are ≤ 2.5 times the upper limit of normal |
Serum creatinine | Serum creatinine > 1.8 mg/dL (159 micromol/L) or creatinine clearance
≤ 60 mL/minute | Withhold Elzonris until serum creatinine resolves to ≤ 1.8 mg/dL (159 micomol/L) or creatinine clearance ≥ 60 ml/minute |
Systolic blood pressure | Systolic blood pressure ≥ 160 mmHg or ≤ 80 mmHg | Withhold Elzonris until systolic blood pressure is < 160 mmHg or > 80 mmHg |
Heart rate | Heart rate ≥ 130 bpm or ≤ 40 bpm | Withhold Elzonris until heart rate is < 130 bpm or > 40 bpm |
Body temperature | Body temperature ≥ 38°C | Withhold Elzonris until body temperature is < 38°C |
Hypersensitivity reactions | Mild or moderate | Withhold Elzonris until resolution of any mild or moderate hypersensitivity reaction. Resume Elzonris at the same infusion rate |
Severe or life-threatening | Discontinue Elzonris permanently |
CLS Management Guidelines
Time of Presentation | CLS Sign/Symptom | Recommended Action | Elzonris Dosing Management |
Prior to first dose of Elzonris in cycle 1 | Serum albumin < 3.2 g/dL | Administer Elzonris when serum albumin ≥ 3.2 g/dL |
During Elzonris dosing | Serum albumin < 3.5 g/dL | Administer 25 g intravenous albumin (q12h or more frequently as practical) until serum albumin is ≥ 3.5 g/dL AND not more than 0.5 g/dL lower than the value measured prior to dosing initiation of the current cycle | Interrupt Elzonris dosing until the relevant CLS sign/symptom has resolve.] |
Serum albumin reduced by ≥ 0.5 g/dL from the albumin value measured prior to Elzonris dosing initiation of the current cycle |
A predose body weight that is increased by ≥ 1.5 Kg over the previous day’s predose weight | Administer 25g intravenous albumin (q12h or more frequently as practical), and manage fluid status as indicated clinically (e.g., generally with intravenous fluids and vasopressors if hypotensive and with diuretics if normotensive or hypertensive), until body weight increase has resolved (i.e. the increase is no longer ≥ 1.5 Kg greater than the previous day’s predose weight). |
Edema, fluid overload and/or hypotension | Administer 25g intravenous albumin (q12h, or more frequently as practical) until serum albumin is ≥ 3.5 g/dL.
Administer 1 mg/kg of methylprednisolone (or an equivalent) per day, until resolution of CLS sign/symptom or as indicated clinically.
Aggressive management of fluid status and hypotension if present, which could include intravenous fluids, and/or diuretics or other blood pressure management, until resolution of CLS sign/symptom or as clinically indicated |
3. Continuation of Elzonris (tagraxofusp-erzs) will be approved annually at the FDA-approved doses if there are no unacceptable toxicities and there is documented evidence of efficacy such as lack of disease progression.
4. Other uses of Elzonris (tagraxofusp-erzs) are considered investigational, including but not limited to acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and myelofibrosis.
Medicare Coverage
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ medical policy.
Medicaid Coverage
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
________________________________________________________________________________________
Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
___________________________________________________________________________________________________________________________
Index:
Tagraxofusp-erzs (Elzonris)
Elzonris (Tagraxofusp-erzs)
Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Natural Killer Cell Leukemia and Lymphoma
References:
1. Stemline Therapeutics,Inc. Elzonris Package Insert. New York,NY. December 2018.
2. Elzonris. Clinicaltrial.gov. Accessed on 1/30/19 . Available at: https://clinicaltrials.gov/ct2/show/NCT02113982
3. Stemline Therapeutics Inc. Clinical Study Report STML-401-0114. SL 401 in patients with acute myeloid leukemia or blastic plasmacytoid dendritic cell neoplasm (updated November 28, 2018)
4. Frankel AE, Woo JH, Ahn C, et al. Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients. Blood. 2014;124(3):385-392.
5. Sullivan, Jill M and David A Rizzieri. “Treatment of blastic plasmacytoid dendritic cell neoplasm” Hematology. American Society of Hematology. Education Program vol. 2016,1 (2016): 16-23.
6. Leukemia and Lymphoma Society. (2015). Blastic Plasmacytoid Dendritic Cell Neoplasm. Retrieved from https://www.lls.org/leukemia/blastic-plasmacytoid-dendritic-cell-neoplasm.
7. Gurbuxani S. Blastic plasmacytoid dendritic cell neoplasm. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://updtodate.com (Accessed on January 27, 2019)
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
.
_________________________________________________________________________________________
Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
____________________________________________________________________________________________________________________________ |