The efficacy of Lumoxiti was demonstrated in a Phase 3 multicenter, single-arm open-label study. Patients received Lumoxiti 40mcg/kg intravenously over 30 minutes on days 1, 3 and 5 of 28 day cycle for a maximum of 6 cycles or until documentation of minimal residual disease-negative complete response, disease progression, initiation of alternate therapy, or unacceptable toxicity. Patients received prophylaxis for renal insufficiency and hypersensitivity reactions. The primary endpoint of the trial was durable complete response. Durable complete response was confirmed by maintenance of hematologic remission (hemoglobin ≥11 g/dL, neutrophils ≥1500/mm³ , and platelets ≥100,000/mm³ without transfusions or growth factor for at least 4 weeks) more than 180 days after the assessed completed response. The durable cure rate was 30%(24/80 patients; 95%CI:20-41).

[INFORMATIONAL NOTE: The FDA approved package insert has the following Black Box Warnings:

• Capillary Leak Syndrome (CLS), including life-threatening cases, occurred in patients receiving Lumoxiti. Delay dosing or discontinue Lumoxiti as recommended.
• Hemolytic Uremic Syndrome (HUS), including life-threatening cases, occurred in patients receiving Lumoxiti. Discontinue Lumoxiti in patients with HUS.]

(Note: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)

1. Moxetumomab Pasudotox-tdfk (Lumoxiti) is medically necessary for the following FDA approved indications when ALL of the following criteria are met:
• For the treatment of treatment relapsed or refractory hairy cell leukemia (HCL)
  • Patient is at least 18 years of age; AND
  • Patient has a confirmed diagnosis of Hairy Cell Leukemia or a HCL variant; AND
  • Patient received ≥ 2 prior systemic therapies
    • Two courses of a purine nucleoside analog(e.g., cladribine,pentostatin, etc.); or
    • One course of rituximab or a BRAF inhibitor(e.g, vemurafenib, dabrafenib, etc.) following a single prior purine nucleoside analog course; AND
  • Patient is does not have severe renal impairment defined as CrCl ≤ 29mL/min; AND
  • Patient must be Pseudomonas-immunotoxin naïve(e.g., moxetumomab pasudotox, etc.); AND
  • Patient has an Eastern Cooperative Oncology Group performance status of 0, 1, or 2; AND
  • The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis

2. When Moxetumomab Pasudotox-tdfk (Lumoxiti) is medically necessary, initial therapy will be approved for 6 months at the FDA recommended dosage of:
• 0.04 mg/kg as an intravenous infusion over 30 minutes on days 1,3, and 5 of each 28 day cycle
• Continuation of a maximum of 6 cycles or until disease progression
  
[INFORMATIONAL NOTE: As per the FDA approved labeling recommended concomitant treatment with the following:
• Hydration
  • Intravenously administer 1 L of isotonic solution (e.g., 5% Dextrose Injection, USP and 0.45% or 0.9% Sodium Chloride Injection, USP) over 2-4 hours before and after each LUMOXITI infusion. Administer 0.5 L to patients under 50 kg.
  • Advise all patients to adequately hydrate with up to 3 L (twelve 8-oz glasses) of oral fluids (e.g., water, milk, or juice) per 24 hours on Days 1 through 8 of each 28-day cycle. In patients under 50 kg, up to 2 L (eight 8-oz glasses) per 24 hours is recommended. Monitor fluid balance and serum electrolytes to avoid fluid overload and/or electrolyte abnormalities
• Thromboprophylaxis
  • Consider low-dose aspirin on Days 1 through 8 of each 28-day cycle.
  • Monitor for signs and symptoms of thrombosis
• Premedication
  • Premedicate 30-90 minutes prior to each Lumoxiti infusion with:
    • An antihistamine (e.g., hydroxyzine or diphenhydramine)
    • Acetaminophen antipyretic
    • A histamine-2 receptor antagonist (e.g., ranitidine, famotidine, or cimetidine)
    • If a severe infusion related reaction occurs, interrupt the Lumoxiti infusion and institute appropriate medical management. Administer an oral or intravenous corticosteroid approximately 30 minutes before resuming, and before each Lumoxiti infusion thereafter
• Post-infusion Medication
  • Consider oral antihistamines and antipyretics for up to 24 hours following Lumoxiti infusions
  • An oral corticosteroid (e.g., 4 mg dexamethasone) is recommended to decrease nausea and vomiting
  • Maintain adequate oral fluid intake
• Monitor for Capillary Leak Syndrome (CLS) and Hemolytic Uremic Syndrome (HUS) and manage adverse reactions by withholding and/or discontinuing Lumoxiti

Table 1: Monitoring for CLS and HUS

	CLS	HUS
Monitoring Parameter	Before every infusion, check: Weight Blood pressure	Before every infusion, check: Hemoglobin levels Platelet count Serum creatinine
Assessment	If weight has increased by 5.5 pounds (2.5 kg) or 5% or greater from Day 1 of the cycle and the patient is hypotensive, promptly check for peripheral edema, hypoalbuminemia, and respiratory symptoms, including shortness of breath and cough. If CLS is suspected, check for a decrease in oxygen saturation and evidence of pulmonary edema and/or serosal effusions	If HUS is suspected, promptly check blood LDH, indirect bilirubin, and blood smear schistocytes for evidence of hemolysis.

The ECOG Scale of Performance Status describes a patient’s level of functioning in terms of their ability to care for themself, daily activity, and physical ability.

GRADE	ECOG PERFORMANCE STATUS
0	Fully active, able to carry on all pre-disease performance without restriction
1	Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2	Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3	Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4	Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5	Dead]



3. Moxetumomab Pasudotox-tdfk (Lumoxit) is considered medically necessary for the off-label indications that are 2A or better recommendations on National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - Moxetumomab pasudotox-tdfk. Available at: http://www.nccn.org/professionals/drug_compendium/content/

4. Moxetumomab Pasudotox-tdfk (Lumoxiti) is considered investigational for use beyond 6 cycles.
5. Other uses Moxetumomab Pasudotox-tdfk (Lumoxiti) are considered investigational.

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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.

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Index:
Moxetumomab Pasudotox (Lumoxiti)
Lumoxiti (Moxetumomab Pasudotox)

References:
1. AstraZeneca. Lumoxiti Package Insert. Wilmington, DE. January 2019.

2. Moxetumomab Pasudotox. Clinicaltrial.gov. Accessed on 9/30/18. Available at: https://clinicaltrials.gov/ct2/show/NCT01829711

3. Kreitman, Robert J. et al. “Moxetumomab Pasudotox in Relapsed/refractory Hairy Cell Leukemia.” Leukemia 32.8 (2018): 1768–1777. PMC. Web. 5 Oct. 2018.

4. ECOG Performance Status - ECOG-ACRIN". ECOG-ACRIN, 2018, https://ecog-acrin.org/resources/ecog-performance-status. Accessed 7 Nov 2018.

5. NCCN Drugs and Biologics Compendium. Lumoxiti. [Available at: http://www.nccn.org/professionals/drug_compendium/mainpage.aspx] Accessed May 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*