Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Moxetumomab pasudotox-tdfk* (e.g., LUMOXITI)

Description:

Moxetumomab pasudotox-tdfk is a CD22-directed cytoxin. Moxetumomab pasudotox-tdfk binds CD22 on the cell surface of B-cells and is internalized. Moxetumomab pasudotox-tdfk internalization results in ADP-ribosylation of elongation factor 2, inhibition of protein synthesis, and apoptotic cell death. This product has received FDA approval for the treatment of relapsed/refractory hairy cell leukemia

Hairy cell leukemia is a rare, slow-growing cancer of the blood in which bone marrow makes too many B cells (lymphocytes), a type of white blood cell that fights infection. These excess B cells are abnormal and look "hairy" under a microscope. As the number of leukemia cells increases, fewer healthy white blood cells, red blood cells and platelets are produced. Hairy cell leukemia affects more men than women, and it occurs most commonly in middle-aged or older adults.

This condition often enters a chronic disease phase with treatment sometimes leading to many years in remission.

Moxetumomab pasudotox-tdfk has a black box warning for capillary leak syndrome (CLS) and hemolytic uremic syndrome (HUS). CLS and HUS, including life-threatening cases, have occurred in patients receiving Moxetumomab pasudotox-tdfk. Monitor weight and blood pressure; if CLS is suspected, check labs, including albumin. Delay dosing or discontinue as recommended. Monitor hemoglobin, platelet count, serum creatinine, and ensure adequate hydration; discontinue in patients with HUS.

Regulatory

In 2018 Moxetumomab pasudotox-tdfk (e.g., Lumoxiti) for injection, for intravenous use was approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory hairy cell leukemia (HCL) who received at least two prior systemic therapies, including treatment with a purine nucleoside analog (PNA).

On November 19, 2022, Astra Zeneca announced voluntary withdrawal of Moxtumomab pasudotox-tdfk (e.g., Lumoxiti) from the U.S. Market in July 2023 due to low clinical updtake. Distribution will stop in August 2023 and AstraZeneca will request returns of the product rom distributors.

Coding

See CPT/HCPCS Code section below.

Policy/
Coverage:

Effective August 1, 2021, for members of plans that utilize an oncology benefits management program, Prior Approval is required for this service and is managed through the oncology benefits management program.

Effective April 15, 2023

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

The use of Moxetumomab pasudotox-tdfk for the treatment of adult individuals with relapsed or refractory hairy cell leukemia (HCL) or any other indication does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For members with contracts without primary coverage criteria, Moxetumomab pasudotox-tdfk, for the treatment of adult individuals with relapsed or refractory hairy cell leukemia (HCL) or any other indication, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective January 2022 to April 14, 2023

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

The use of Moxetumomab pasudotox-tdfk meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the treatment of adult patients (18 years and older) with relapsed or refractory hairy cell leukemia (HCL) (FDA Lumoxiti, 2018) who meet ALL the following:

INITIAL APPROVAL

Confirmed diagnosis of Hairy Cell Leukemia (Kreitman, 2020) with one or more of the following indications for treatment:

Significant cytopenias (Kreitman, 2020):

Absolute Neutrophils Count (ANC) <1000/microL; or
Platelets <100,000/microL; or
Hemoglobin less than 11 g/dl;

Symptomatic splenomegaly (Kreitman, 2020).

AND

Must have relapsed or refractory disease with failure of at least two prior systemic therapies, including at least one purine analog (e.g., cladribine, pentostatin, etc.) (NCCN 2A; FDA Lumoxiti, 2018); AND
ECOG performance status 0-2 (FDA Lumoxiti, 2018); AND
Used as a single agent (NCCN 2A; FDA Lumoxiti, 2018);

AND

Member does not have severe renal impairment (e.g., CrCl less than 30 mL/min (FDA, Lumoxiti, 2018).

* The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:

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, for example, light housework, office work
2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5 = Dead

Coverage is provided for six months (6 cycles) only (unless there is evidence of complete remission, disease progression on treatment, or unacceptable toxicity).

The use of this drug is covered if an FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).

Dosage and Administration

Lumoxiti is available as a 1 mg single-dose vial for reconstitution and further dilution.
Recommended dosage: 0.04 mg/kg as an intravenous infusion over 30 minutes on Days 1,3, and 5 of each 28-day cycle.
Maintain adequate hydration throughout treatment.
Consider low-dose aspirin on Days 1 to 8 of each 28-day cycle.
Premedicated with an acetaminophen antipyretic, antihistamine, and H2-receptor antagonist prior to all infusions.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

The use of Moxetumomab pasudotox-tdfk for any other indication does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For members with contracts without primary coverage criteria, Moxetumomab pasudotox-tdfk is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective June 1, 2021 through December 31, 2021

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

The use of Moxetumomab pasudotox-tdfk (Lumoxiti) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the treatment of adult patients with relapsed or refractory hairy cell leukemia (HCL) who meet ALL the following:

INITIAL APPROVAL CRITERIA:

18 years of age AND
Confirmed diagnosis of Hairy Cell Leukemia with one or more of the following indications for treatment:

A. Significant cytopenias:

Absolute Neutrophils Count (ANC) <1000/microL
Platelets <100,000/microL
Hemoglobin <11 g/dL, OR

B. Symptomatic splenomegaly or lymphadenopathy, OR

C. Constitutional symptoms such as weight loss, night sweats, and/or fever.

Must have relapsed or refractory disease with failure of at least two prior systemic therapies, including at least one purine analog (e.g., cladribine, pentostatin, etc.) AND
*ECOG performance status 0-2, AND
Used as a single agent

* The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:

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, for example, light housework, office work
2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5 = Dead

Coverage is provided for six months (6 cycles) only (unless there is evidence of complete remission, disease progression on treatment, or unacceptable toxicity).

The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).

Dosage and Administration

Lumoxiti is available as a 1 mg single-dose vial for reconstitution and further dilution.

Recommended dosage: 0.04 mg/kg as an intravenous infusion over 30 minutes on Days 1,3, and 5 of each 28-day cycle.

Maintain adequate hydration throughout treatment.

Consider low-dose aspirin on Days 1 to 8 of each 28-day cycle.

Premedicated with an acetaminophen antipyretic, antihistamine, and H2-receptor antagonist prior to all infusions.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

The use of Moxetumomab pasudotox-tdfk (Lumoxiti) for any other indication does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness AND

Not covered for members with severe renal chronic kidney disease (e.g. CrCl < 30 mlLmin.

For members with contracts without primary coverage criteria, Moxetumomab pasudotox-tdfk (Lumoxiti) is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:

Hairy cell leukemia (HCL) is an indolent B-cell malignancy characterized by high initial sensitivity to purine analog chemotherapy, minimal residual disease (MRD) frequently accompanying complete remission (CR), and relapses requiring additional treatment. Repeat chemotherapy shows decreasing efficacy and increasing toxicity with each course. Newer therapies targeting BRAF/MEK or Bruton's tyrosine kinase are effective but generally leave MRD. Rituximab has modest activity as a single agent and can achieve MRD-negative CR in combination with purine analogs, but there is significant toxicity from the chemotherapy. Moxetumomab pasudotox-tdfk (Moxe) is a biologic containing an antibody fragment (Fv) binding to CD22, attached to a portion of Pseudomonas exotoxin A. Binding to CD22 enables the toxin to enter and kill cells. Moxe is administered by 30-minute infusions on days 1, 3, and 5 of up to six cycles spaced 4 weeks apart. In phase I testing, 64% of 33 patients at the highest dose level achieved CR, most without MRD. Lack of MRD correlated with prolonged CR duration; of 11 MRD-negative CRs, 10 were still in CR after a median of 42 months of observation. In pivotal testing, 75% of 80 patients had a hematologic response, 41% with CR; 82% (27/33) of CRs were MRD-negative, and only 4 of the 27 MRD-negative patients relapsed during the follow-up period. Hemolytic uremic syndrome and capillary leak syndrome were each observed in 9% of patients, all reversible. In September 2018, the U.S. Food and Drug Administration approved Moxe for the treatment of relapsed/refractory HCL after ≥2 prior therapies. Moxe is undergoing further development in combination with rituximab. IMPLICATIONS FOR PRACTICE: Hairy cell leukemia (HCL) has effective treatments including purine analogs with and without rituximab, and oral inhibitors of BRAF, MEK and Bruton's tyrosine kinase (BTK). Despite these therapies, relapse occurs, and moxetumomab pasudotox has an important role in relapsed and refractory HCL because of its ability to achieve high rates of complete remissions (CRs) without chemotherapy; most of these CRs are without minimal residual disease (MRD). CR duration is enhanced in patients who achieve eradication of MRD. To improve the efficacy of this recombinant immunotoxin, a phase I trial is underway in combination with rituximab to reduce tumor burden and decrease immunogenicity. (Kreitman RJ, Pastan I., 2020)

This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B cell malignancy with high CD22 expression. The study enrolled patients with relapsed/refractory HCL who had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 every 28 days for ≤6 cycles. Blinded independent central review determined disease response and minimal residual disease (MRD) status. Among 80 patients (79% males; median age, 60.0 years), durable complete response (CR) rate was 30%, CR rate was 41%, and objective response rate (CR and partial response) was 75%; 64 patients (80%) achieved hematologic remission. Among complete responders, 27 (85%) achieved MRD negativity by immunohistochemistry. The most frequent adverse events (AEs) were peripheral edema (39%), nausea (35%), fatigue (34%), and headache (33%). Treatment-related serious AEs of hemolytic uremic syndrome (7.5%) and capillary leak syndrome (5%) were reversible and generally manageable with supportive care and treatment discontinuation (6 patients; 7.5%). Moxetumomab pasudotox treatment achieved a high rate of independently assessed durable response and MRD eradication in heavily pretreated patients with HCL, with acceptable tolerability. (Kreitman RJ, Dearden C, Zinzani PL, 2018)

2022 Update

Annual policy review completed with a literature search using the MEDLINE database through March 2022. No new literature was identified that would prompt a change in the coverage statement.

January 2023 Update

On November 19, 2022, AstraZeneca announced voluntary withdrawal of Moxetumomab pasudotox-tdfk (e.g., Lumoxiti) from the U.S. market in July 2023 due to low clinical uptake. Distribution will stop in August 2023 and AstraZeneca will request returns of the product from distributors.

2023 Update

Annual policy review completed with a literature search using the MEDLINE database through March 2023.

2024 Update

Annual policy review completed with a literature search using the MEDLINE database through February 2024.

CPT/HCPCS:

References:

Cortelezzi A, Dinner S, Doubek M, et.al.,(2018) Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 2018 Aug;32(8):1768-1777. doi: 10.1038/s41375-018-0210-1. Epub 2018 Jul 20. PMID: 30030507; PMCID: PMC6087717.

Kreitman RJ, Dearden C, Zinzani PL, et.al.,(2018) Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 2018 Aug;32(8):1768-1777. doi: 10.1038/s41375-018-0210-1. Epub 2018 Jul 20. PMID: 30030507; PMCID: PMC6087717.

Kreitman RJ, Pastan I.(2020) Contextualizing the Use of Moxetumomab Pasudotox in the Treatment of Relapsed or Refractory Hairy Cell Leukemia. Oncologist. 2020 Jan;25(1):e170-e177. doi: 10.1634/theoncologist.2019-0370. Epub 2019 Oct 18. PMID: 31628266; PMCID: PMC6964124

Lumoxiti [package insert]. Wilmington, DE; Astra Zeneca Pharmaceuticals; April 2020. Accessed February 17, 2021.

National Comprehensive Cancer Network (NCCN). Hairy Cell Leukemia. NCCN Clinical Practice Guidelines in Oncology, Accessed February 17, 2021.

Tallman MS, Aster JC.(2021) Treatment of hairy cell leukemia. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed January 2021.

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association.