Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Isatuximab-irfc (Sarclisa®)

Policy #:08.00.46



The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract. The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Isatuximab-irfc (Sarclisa®) is considered medically necessary and, therefore, covered for the treatment of adult individuals with refractory, relapsed, or progressive multiple myeloma, in combination with pomalidomide (Pomalyst®) and dexamethasone, after receiving at least two prior therapies including lenalidomide (Revlimid®) and a proteasome inhibitor (e.g., bortezomib [Velcade®], carfilzomib [Kyprolis®], ixazomib [Ninlaro®]).

EXPERIMENTAL/INVESTIGATIONAL

All other uses for isatuximab-irfc (Sarclisa®) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.


Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract,
isatuximab-irfc (Sarclisa®) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Isatuximab-irfc (Sarclisa®) was approved by the FDA on March 2, 2020 in combination with pomalidomide and dexamethasone, for the treatment of adult individuals with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. Isatuximab-irfc (Sarclisa®) is administered as an intravenous infusion. The safety and effectiveness in pediatric individuals have not been established.

Description

Multiple myeloma is a cancer that is created from plasma cells with abnormal genetic variations. Normally, plasma cells grow and divide to make new cells; once cells grow old or get damaged, they die. In contrast, due to the genetic variations in multiple myeloma, the myeloma cells replicate uncontrollably throughout the bone marrow, don't die quickly when old or damaged, crowd-out normal blood cells in the bone marrow as they grow, and destroy the bone tissue. The antibodies synthesized by myeloma cells do not fight infections like normal antibodies do. Common signs and symptoms include anemia, bone pain, kidney damage due to elevated creatinine or serum protein, infection, fatigue, and hypercalcemia.

Like many types of malignancies, further treatment of multiple myeloma after relapsed, progressive, or refractory disease usually yields a shorter duration and lower quality of response compared to the initial response. There is a high demand for agents that treat multiple myeloma that do not respond or that progress after first- or subsequent-line therapy.

Isatuximab-irfc (Sarclisa®) was approved by the US Food and Drug Administration (FDA) on March 2, 2020 in combination with pomalidomide and dexamethasone for the treatment of adult individuals with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
Isatuximab-irfc (Sarclisa®) is a CD38-directed cytolytic antibody. CD38 is a glycoprotein expressed on the surface of hematopoietic cells (including lymphoid and myeloid cells) and tumor cells. When multiple myeloma is present, there is an overexpression of CD38 on malignant plasma cells. Isatuximab-irfc (Sarclisa®) works by binding to CD38 and induces apoptosis of tumor cells and activation of immune effector mechanisms including complement-dependent cytotoxicity (CDC) (causing tumor cell lysis and death), antibody-dependent cell-mediated cytotoxicity (ADCC) (causing tumor cell death by non-phagocytic processes via the activation of natural killer cells, macrophages, etc.), and antibody-dependent cellular phagocytosis (ADCP) by macrophages. The combination of isatuximab-irfc (Sarclisa®) and pomalidomide enhanced ADCC activity and direct tumor cell killing compared to that of isatuximab-irfc (Sarclisa®) alone in vitro, and the combination of isatuximab-irfc (Sarclisa®) and pomalidomide also enhanced antitumor activity compared to the activity of isatuximab-irfc (Sarclisa®) or pomalidomide alone in a human multiple myeloma xenograft model.

PEER-REVIEWED LITERATURE
Summary

The safety and efficacy of isatuximab-irfc (Sarclisa®) were evaluated in ICARIA-MM (Attal et al 2019), a multicenter, multinational, randomized (1:1), open-label, two-arm, phase 3 study in 307 adult individuals with relapsed and refractory multiple myeloma. Individuals had received at least two prior therapies including lenalidomide and a proteasome inhibitor (e.g., bortezomib [Velcade®], carfilzomib [Kyprolis®], ixazomib [Ninlaro®]). The median number of prior lines of therapy was 3 (range 2-11). All participants received a prior proteasome inhibitor, all participants received prior lenalidomide, and 56% of participants received prior stem cell transplantation; the majority of participants (93%) were refractory to lenalidomide, 76% to a proteasome inhibitor, and 73% to both an immunomodulator and a proteasome inhibitor. The median age was 67 years (range 36-86).

Participants received either isatuximab-irfc (Sarclisa®) 10 mg/kg (as an intravenous infusion weekly in the first cycle and every two weeks thereafter) in combination with pomalidomide 4 mg and dexamethasone 40 mg (20 mg for individuals aged ≥75 years) (Isa-Pd, N=154) or pomalidomide 4 mg and dexamethasone 40 mg (Pd, N=153). Treatment was administered in both groups in 28-day cycles until disease progression or unacceptable toxicity, or consent withdrawal.

The primary outcome of this study was progression-free survival (PFS). At a median follow-up time of 11.6 months, the Isa-Pd group had a higher median progression-free survival (11.5 versus 6.5 months, p=0.001) compared to the Pd group. PFS benefit with Isa-Pd occurred in the following prespecified subgroups: individuals with poor prognosis, aged 75 years or older, disease refractory to lenalidomide, a proteasome inhibitor, both lenalidomide and a proteasome inhibitor, or to lenalidomide at the last line prior to study entry. The median duration of treatment was 41 weeks for the Isa-Pd group compared to 24 weeks for the Pd group. There was a high number of participants who discontinued treatment: 87 out of 152 individuals in the Isa-Pd group and 114 out of 149 individuals in the Pd group, although all 307 individual were included in the intention-to-treat analysis. The most frequent treatment-emergent adverse events (any grade) were infusion reactions, upper respiratory tract infections, and diarrhea.

OFF-LABEL INDICATION

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References

Attal M, Richardson PG, Rajkumar SV, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multple myeloma (ICARIA-MM): a randomized, multicenter, open-label, phase 3 study. Lancet. 2019;394(10214):2096-2107.


Elsevier’s Clinical Pharmacology Compendium. isatuximab-irfc (Sarclisa®). 03/06/2020. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed March 10, 2020.

Lexi-Drugs Compendium. isatuximab-irfc (Sarclisa®). 03/09/2020. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 10, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. isatuximab-irfc (Sarclisa®). [NCCN Web site]. 2020. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed March 24, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Multiple Myeloma. V.3.2020. 03/10/2020. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf [via free subscription]. Accessed March 24, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines for Patients - Multiple Myeloma. 2019. [NCCN Web site]. Available at: https://www.nccn.org/patients/guidelines/content/PDF/myeloma-patient.pdf [via free subscription]. Accessed March 10, 2020.

National Institutes of Health. Clinical trials: Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients (ICARIA-MM)(NCT02990338). [ClinicalTrials Web site]. last updated 03/05/2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02990338?term=NCT02990338&draw=2&rank=1 . Accessed March 10, 2020.

Rajkumar SV. Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis. [UpToDate Web Site]. Updated 01/09/2020. Available at: http://www.uptodate.com/home [via subscription only]. Accessed March 10, 2020.

Rajkumar SV. Multiple myeloma: Treatment of relapsed or refractory disease. [UpToDate Web site]. 01/28/2020. Available at: http://www.uptodate.com/contents/treatment-of-relapsed-or-refractory-multiple-myeloma?source=search_result&search=daratumumab&selectedTitle=4%7E10. Accessed March 4, 2020.

Truven Health Analytics. Micromedex® DrugDex® Compendium. isatuximab-irfc (Sarclisa®). 03/04/2020. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 10, 2020.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. isatuximab-irfc (Sarclisa®) prescribing information and approval letter [FDA Web site]. 03/02/2020. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed March 2, 2020.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)



N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

C90.00 Multiple myeloma not having achieved remission

C90.01 Multiple myeloma in remission

C90.02 Multiple myeloma in relapse



HCPCS Level II Code Number(s)



THE FOLLOWING CODE(S) ARE USED TO REPRESENT ISATUXIMAB-IRFC (SARCLISA®)

C9399 Unclassified drugs or biologics

J3590 Unclassified biologics


Revenue Code Number(s)


N/A



Misc Code

N/A:

N/A


Coding and Billing Requirements

BILLING REQUIREMENTS

If there is no specific HCPCS code available for the drug administered, then the drug must be reported with the most appropriate unlisted code along with the corresponding National Drug Code (NDC).
Cross References


Policy History

08.00.46
05/11/2020The following new policy has been developed to communicate the Company's coverage criteria for isatuximab-irfc (Sarclisa®).
Version Effective Date: 05/11/2020
Version Issued Date: 05/11/2020
Version Reissued Date: N/A



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