CurrentmhnPolicy CP.PHAR.482

Isatuximab-irfc (Sarclisa)

Defines medical necessity criteria, initial and continued approval requirements, dosing limits, covered combinations/indications, exclusions, prior authorization and documentation expectations for isatuximab-irfc (Sarclisa) across commercial, HIM and Medicaid lines of business.

Policy Summary

Payermhn

PolicyIsatuximab-irfc (Sarclisa)

Policy CodePolicy CP.PHAR.482

Change TypeMultiple indication and coding updates (2021-2025)

Effective DateJun 1, 2020

Next Review Date

Key ActionProvider must submit documentation (office notes, lab results or other clinical information) supporting that member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

Added indication in transplant-ineligible primary therapy in combination with bortezomib, lenalidomide, and dexamethasone per NCCN 2A recommendation (2024).

Added combination use with carfilzomib and dexamethasone for relapsed/refractory MM after 1 to 3 prior lines of therapy (2021).

Added off-label indication for primary therapy in combination with carfilzomib, lenalidomide, and dexamethasone per NCCN Compendium (2025).

Added HCPCS code J9227 for isatuximab (2021).

3FDA-approved combination indications listed

1Off-label primary therapy combination listed (requires evidence)

10 mg/kg

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Standard maximum dose (per schedule)

J9227HCPCS drug code

Coverage Summary

Policy Number: CP.PHAR.482; Effective Date: 06.01.20. Isatuximab-irfc (Sarclisa) is covered with criteria for multiple myeloma (MM) consistent with FDA-approved and NCCN-recommended regimens. Covered combinations include: isatuximab + pomalidomide + dexamethasone (for patients with ≥2 prior therapies including lenalidomide and a proteasome inhibitor), isatuximab + carfilzomib + dexamethasone (for relapsed/refractory MM after 1–3 prior lines), and isatuximab + bortezomib + lenalidomide + dexamethasone for newly diagnosed MM in patients not eligible for autologous stem cell transplant (ASCT). An off-label primary therapy combination with carfilzomib, lenalidomide, and dexamethasone is listed but requires the prescriber to submit supporting evidence. Coverage is subject to the policy's specified dosing, prior therapy, prescriber, and documentation requirements.

Age>= 18 years

Initial maximum dosing10 mg/kg per week for the first 4 weeks, then every 2 weeks thereafter

Continued therapy dosing limitStandard: 10 mg/kg every 2 weeks; for bortezomib/lenalidomide/dexamethasone regimen: 10 mg/kg every 2 weeks, then every 4 weeks starting Cycle 18

Minimum prior therapy for pomalidomide combinationAt least 2 prior therapies including lenalidomide and a proteasome inhibitor

Prior lines for carfilzomib combinationRelapsed/refractory disease after 1 to 3 prior lines of therapy

Minimum prior exposure before continued therapy>= 30 days on Sarclisa

Initial Therapy Criteria — Multiple Myeloma

I. Initial Approval Criteria - Multiple Myeloma

Coverage when ALL of the following are met:

ALL of the following

Diagnosis of multiple myeloma (MM)
Prescriber specialty: Prescribed by or in consultation with an oncologist or hematologist
Age >= 18 years>= 18 years
Sarclisa prescribed in one of the following ways (select one)

Initial Therapy Criteria — Other Indications

I. Initial Approval Criteria - Other diagnoses/indications

If not meeting the MM criteria above, must meet ONE of the following:

Alternate paths for other diagnoses/indications

Recent label change (formulary): If drug label changed within last 6 months and policy not updated, follow relevant formulary/no-coverage or non-formulary policy per line of business (references: CP.CPA.190, HIM.PA.33, CP.PMN.255 for formulary; CP.CPA.190, HIM.PA.103, CP.PMN.16 for non-formulary)
Operational: cite referenced policy codes for line-of-business handling
Off-label policy: If requested use not listed under section III and criterion 1 above does not apply, refer to off-label use policy per line of business (CP.CPA.09; HIM.PA.154; CP.PMN.53)
Operational: off-label use requires following referenced off-label policies

Continuation Therapy Criteria — Multiple Myeloma

II. Continued Therapy - Multiple Myeloma

Continued coverage when ALL of the following are met:

ALL of the following

Current therapy or minimum exposure: Member is currently receiving medication via Centene benefit, or documentation supports member has received Sarclisa for a covered indication for at least 30 daysMinimum prior exposure before continued therapy: >= 30 days
Response: Member is responding positively to therapy
If request is for a dose increase, must meet one of:
- Pomalidomide or carfilzomib combinations dose:

Continuation Therapy — Other Indications

II. Continued Therapy - Other diagnoses/indications

If not meeting continued therapy MM criteria above, must meet ONE of the following:

Alternate paths for other continued therapy diagnoses/indications

Recent label change (formulary) continued: If drug label changed within last 6 months and policy not updated, follow relevant formulary/no-coverage or non-formulary policy per line of business (references as in Initial section)
Operational: reference same policy codes as Initial section
Off-label policy continued: If requested use not listed under section III and criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.

Diagnoses / Indications Not Authorized

Applicable Codes

HCPCS - Drug codeHCPCSCovered

J9227

Injection, isatuximab-irfc, 10 mg

Billing note: Sarclisa is supplied in single‑dose vials of 100 mg and 500 mg. Claims should reflect dosing per kg on the claim and use HCPCS J9227 (10 mg) with the appropriate quantity to represent the milligrams administered.

Provider Actions / Prior Authorization

Prior Authorization

Prior authorization required

Prior authorization may be required for Sarclisa and for listed prior therapies per plan processes. Providers should anticipate PA requirements for lenalidomide, bortezomib, carfilzomib (Kyprolis), and ixazomib (Ninlaro) when requesting coverage for isatuximab-containing regimens or when documenting prior lines of therapy.

lenalidomide
bortezomib
carfilzomib (Kyprolis)
ixazomib (Ninlaro)

Documentation Required

Submit supporting documentation

Submit supporting documentation such as office chart notes, laboratory results, and other clinical information that demonstrate the member meets all approval criteria for Sarclisa (diagnosis, prior therapies, prescriber specialty, age, dosing, and regimen requirements).

Clinical Evidence & References

Primary evidence sources used to align coverage: Sanofi Sarclisa Prescribing Information (October 2024); key clinical trial ICARIA-MM (Lancet 2019) evaluating isatuximab + pomalidomide + dexamethasone; and the NCCN Multiple Myeloma Version 1.2025 guideline/compendium.

Background

Isatuximab-irfc (Sarclisa) is a CD38-directed cytolytic antibody indicated in combination regimens for adult patients with multiple myeloma. This policy aligns coverage to FDA-approved indications and NCCN recommendations, and specifies dosing schedules, duration (treat until disease progression or unacceptable toxicity), and prior therapy requirements. Definitions: MM = multiple myeloma; PI = proteasome inhibitor (e.g., bortezomib, carfilzomib, ixazomib); ASCT = autologous stem cell transplant.

Revision History

02.02.24annual_review

2Q 2024 annual review: added indication for primary therapy in transplant candidates in combination with bortezomib, lenalidomide, and dexamethasone per NCCN 2A recommendation; references reviewed and updated.

12.09.24rt4_fda_approval

RT4 entry (12.09.24): added newly FDA-approved indication for primary therapy for multiple myeloma patients not eligible for autologous stem cell transplant (combination with bortezomib, lenalidomide, and dexamethasone).

12.07.21rt4_addition

Policy Summary

Payermhn

PolicyIsatuximab-irfc (Sarclisa)

Policy CodePolicy CP.PHAR.482

Change TypeMultiple indication and coding updates (2021-2025)

Effective DateJun 1, 2020

Next Review Date

Key ActionProvider must submit documentation (office notes, lab results or other clinical information) supporting that member meets all approval criteria.

SourceLink

On This Page

Pomalidomide combination: In combination with pomalidomide and dexamethasone, after 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI)Minimum prior therapy: at least 2 prior therapies including lenalidomide and a PI

Carfilzomib combination (relapsed/refractory): In combination with carfilzomib and dexamethasone, for relapsed or refractory disease after 1 to 3 prior lines of therapyPrior lines: 1 to 3

VRd primary therapy (ASCT-ineligible): In combination with bortezomib, lenalidomide, and dexamethasone, for primary therapy (for patients not eligible for autologous stem cell transplant)

Carfilzomib+lenalidomide+dexamethasone (off-label): In combination with carfilzomib, lenalidomide, and dexamethasone, for primary therapy (off-label) - prescriber must submit supporting evidence

Off-label regimen requires supporting practice guideline or peer-reviewed literature

Dose requirement (select one)

Standard dosing: Dose does not exceed 10 mg/kg per week for the first 4 weeks, then every 2 weeks thereafterInitial maximum dosing: 10 mg/kg per week for first 4 weeks, then every 2 weeks thereafter
Off-label dosing evidence: Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Regimen requirement: Prescribed regimen must be FDA-approved or recommended by NCCN

In combination with dexamethasone and pomalidomide or carfilzomib: new dose does not exceed 10 mg/kg every 2 weeks

Continued therapy dosing limit (standard): 10 mg/kg every 2 weeks

Lenalidomide+bortezomib+dexamethasone regimen dose: In combination with dexamethasone, lenalidomide, and bortezomib: new dose does not exceed 10 mg/kg every 2 weeks, then every 4 weeks starting Cycle 18 and beyondFor bortezomib/lenalidomide/dexamethasone: 10 mg/kg every 2 weeks then every 4 weeks starting Cycle 18

Off-label dosing evidence: New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Regimen requirement: Prescribed regimen must be FDA-approved or recommended by NCCN

Documentation Required

Evidence for off-label dosing or use

For requests involving off-label regimens or dose increases, the prescriber must submit supporting evidence from practice guidelines or peer-reviewed literature demonstrating that the proposed dosing or use is appropriate and supported.

Billing Rule

Dose reporting / Billing

Use HCPCS code J9227 (10 mg) when billing isatuximab. Calculate billed quantity to reflect the ordered mg/kg dose and the total milligrams administered. Single-dose vial sizes available are 100 mg and 500 mg; plan claims should account for vial sizes when reporting quantities.

J9227

Denial Risk

Non-covered indications

Requests for non–FDA approved indications that are not addressed in this policy will be denied unless sufficient documentation of efficacy and safety is provided in accordance with the off-label use policies referenced by line of business.

RT4 (12.07.21): criteria added for FDA‑approved indication — combination use with carfilzomib (Kyprolis) and dexamethasone for relapsed or refractory multiple myeloma after 1 to 3 prior lines of therapy; maximum dose criteria updated to require every‑2‑week dosing after the first cycle per prescribing information.

02.12.21hcpcs_addition

2Q 2021 annual review: added HCPCS code J9227 (Injection, isatuximab‑irfc, 10 mg); references reviewed and updated.

02.14.25annual_reviewLatest

2Q 2025 annual review: added off‑label primary therapy indication for combination with carfilzomib (Kyprolis), lenalidomide, and dexamethasone per NCCN Compendium; references reviewed and updated. P&T approval recorded 05.25.