Centene daratumumab Coverage Prior Auth Policy

Coverage Criteria for Daratumumab Products

Initial Approval — Multiple Myeloma

Covered when ALL of the following are met:

Initial MM criteria: 1) Diagnosis of multiple myeloma; 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) Prescribed as primary therapy in one of the specified combination regimens OR as subsequent therapy in one of the specified combination regimens OR as monotherapy after ≥3 prior lines including a proteasome inhibitor and an immunomodulatory agent or for double‑refractory disease; 5) Dose does not exceed FDA maximum or is supported by practice guidelines or peer‑reviewed literature for off‑label uses (prescriber must submit supporting evidence); 6) Prescribed regimen must be FDA‑approved or recommended by the NCCN compendium.

Primary therapy regimens include: (a) for patients ineligible for ASCT — daratumumab in combination with lenalidomide and dexamethasone OR bortezomib, melphalan, and prednisone; (b) for patients eligible for ASCT — daratumumab in combination with bortezomib/thalidomide/dexamethasone OR bortezomib/lenalidomide/dexamethasone, etc. Subsequent therapy regimens include combinations with dexamethasone and lenalidomide, bortezomib (with or without cyclophosphamide), carfilzomib, pomalidomide, Venclexta/Xpovio as referenced in policy.

Initial Approval — Systemic Light Chain (AL) Amyloidosis

Covered when ALL of the following are met:

AL amyloidosis criteria: 1) Diagnosis of systemic light‑chain (AL) amyloidosis; 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age > 18 years; 4) Daratumumab or Darzalex Faspro is prescribed in one of the following: (a) in combination with bortezomib, cyclophosphamide, and dexamethasone; (b) in combination with lenalidomide and dexamethasone; (c) as a single agent for newly diagnosed disease if the member has significant neuropathy or Mayo stage IIIb disease (off‑label per NCCN); (d) as single agent for relapsed or refractory disease after ≥1 prior therapy (off‑label); 5) Dose within FDA maximum limit for any FDA‑approved indication or supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence); 6) Prescribed regimen must be FDA‑approved or recommended by NCCN compendium.

Prior authorization may be required; continued approval may require confirmatory evidence for accelerated approvals per product labeling.

Initial Approval — Off‑label: T‑cell Acute Lymphoblastic Leukemia (T‑ALL)

Covered when ALL of the following are met:

T‑ALL criteria: 1) Diagnosis of T‑cell acute lymphoblastic leukemia (T‑ALL) with relapsed or refractory disease; 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Prescribed as part of a daratumumab‑containing regimen (e.g., daratumumab plus vincristine, pegaspargase/calaspargase, doxorubicin, and prednisone or dexamethasone); 4) Dose is within FDA maximum limit for any FDA‑approved indication or is supported by practice guidelines or peer‑reviewed literature for the off‑label use (prescriber must submit supporting evidence); 5) Prescribed regimen must be FDA‑approved or recommended by the NCCN compendium.

This is an off‑label indication; coverage follows NCCN compendium support and requires documentation of supporting evidence.

Covered indications with criteria referenced

Coverage aligns with FDA‑approved indications and NCCN Compendium‑supported regimens; monotherapy and combination uses vary by line of therapy and transplant eligibility.

MM — induction/consolidation: Daratumumab (IV or SC) is supported in combination regimens for newly diagnosed multiple myeloma including induction/consolidation for patients eligible for autologous stem cell transplant (e.g., in combination with bortezomib, lenalidomide, and dexamethasone) as reflected in FDA labeling and the NCCN compendium.

RT4 additions and NCCN updates added Darzalex Faspro for induction/consolidation regimens.

MM — subsequent therapy: Daratumumab is supported as subsequent therapy in combination with agents such as pomalidomide, carfilzomib, dexamethasone and other NCCN‑supported combinations; monotherapy is allowable only after ≥3 prior lines including a proteasome inhibitor and an immunomodulatory agent or if double‑refractory.

3Q annual reviews added subsequent therapy combinations and clarified monotherapy sequencing.

Systemic light‑chain (AL) amyloidosis: Daratumumab and Darzalex Faspro are supported for AL amyloidosis in combination regimens (e.g., with bortezomib/cyclophosphamide/dexamethasone) and in select single‑agent NCCN‑supported presentations (e.g., significant neuropathy or Mayo stage IIIb).

Requests for uses that are not FDA‑approved and are not specifically addressed in this policy are not authorized unless the prescriber supplies sufficient documentation demonstrating efficacy and safety per the applicable off‑label use policies (for example, CP.CPA.09 for commercial, HIM.PA.154 for the marketplace, or CP.PMN.53 for Medicaid) or unless coverage is established in an evidence of coverage document.

Daratumumab is contraindicated in individuals with a history of hypersensitivity to daratumumab or any of its components. Hypersensitivity reactions are listed as a contraindication in the policy appendices and must be considered prior to administration.

As a complement to the coverage exclusions above, any request for a non‑FDA indication that is not described in this policy will be considered not authorized unless the provider submits adequate supporting evidence of efficacy and safety consistent with the referenced off‑label use policies.

Codes listed in this clinical policy are provided for informational purposes only; inclusion or exclusion of a code does not guarantee coverage. Providers must follow current professional coding guidance when submitting claims, and claims may be denied if coding is incorrect or inconsistent with coverage determinations.

Initial Therapy Rules

Initial Therapy — top-level rules for daratumumab use

Initial authorization is provided when ALL of the following general rules are satisfied:

General initial therapy rules: 1) Prescribed by or in consultation with an oncologist or hematologist; 2) Diagnosis appropriate for the requested indication per policy (e.g., multiple myeloma, AL amyloidosis, or NCCN‑supported off‑label use); 3) Age criteria met (typically ≥ 18 years unless otherwise specified); 4) Regimen matches an FDA‑approved indication or an NCCN‑recommended regimen for the requested indication; 5) Dose and schedule conform to product labeling (e.g., IV 16 mg/kg regimens or SC fixed 1,800 mg + 30,000 units) or are supported by guidelines/peer‑reviewed literature for off‑label uses (prescriber must submit supporting evidence); 6) Prior authorization documentation includes diagnosis, prior therapies and line(s) of therapy as applicable.

Typical initial approval duration is 6 months. Monotherapy is reserved for later lines per sequencing rules; prior exposure to specified agents may be required depending on indication and line of therapy.

Initial therapy — induction/regimen references

Initial/induction regimen support must match FDA labeling or NCCN recommendations:

Criteria for Continued Therapy

Continued Therapy (All Indications)

Covered when ALL of the following are met for continued authorization:

Continued therapy general: 1) Member is currently receiving daratumumab via the Centene benefit or documentation supports current use and member has received daratumumab for at least 30 days; 2) Member is responding positively to therapy as documented by the prescriber; 3) Current dose does not exceed the maximum indicated regimen in the product labeling; 4) If a dose increase is requested, the new dose is within FDA limits or supported by practice guidelines or peer‑reviewed literature for off‑label uses (prescriber must submit supporting evidence); 5) Prescribed regimen remains FDA‑approved or recommended by NCCN compendium.

Approval duration for continued therapy: 12 months.

Continued Therapy — continuation criteria

Continuation requests must demonstrate ongoing benefit and adherence to dosing guidance:

Continuation response and monitoring: 1) Documentation shows member is responding positively to therapy (clinical or laboratory evidence as provided by prescriber); 2) Member has been on therapy ≥30 days prior to the request for continuation; 3) No dose exceeds the maximum indicated regimen in product labeling; 4) Any requested dose increase is supported by practice guidelines or peer‑reviewed literature for off‑label uses (prescriber must provide evidence); 5) Prescribed regimen must be FDA‑approved or NCCN‑recommended.

Provider Actions, Prior Authorization & Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for daratumumab (Darzalex, Darzalex Faspro). Daratumumab is considered medically necessary only when the member meets all policy criteria for the requested indication and dosing regimen.

PA must document diagnosis, line(s) of therapy, prior agents tried and response or intolerance, prescriber specialty (oncologist/hematologist), and proposed regimen and dosing.
PA requests for non‑FDA (off‑label) indications must include supporting evidence per applicable off‑label policies (e.g., NCCN, peer‑reviewed literature) and reference CP.CPA.09, HIM.PA.154, or CP.PMN.53 as applicable.

Documentation Required

Dosing and Indication Documentation

Prescriber must document that the requested daratumumab regimen matches an FDA‑approved indication or an NCCN‑supported regimen for off‑label use. Dosing and administration must follow the package insert: IV dosing 16 mg/kg per labeled schedule; subcutaneous dosing 1,800 mg daratumumab with 30,000 units hyaluronidase per labeled schedule.

Coding and Dosing References

HCPCS codes referencedHCPCS

J9144	Injection,daratumumab,10 mg and hyaluronidase-fihi
J9145	Injection,daratumumabl0 mg

Common dosing thresholds

IV dosing threshold16 mg/kg IV (common regimens per prescribing information)

SC fixed-dose threshold1,800 mg daratumumab subcutaneously + 30,000 units hyaluronidase (fixed SC formulation)

SC administration site and timeAdministered into the abdomen over approximately 3 to 5 minutes per product labeling

Step Therapy and Prior Treatments

Prior agent / class	Required prior exposure or failure
Lenalidomide (immunomodulatory agent)	Prior exposure required for many subsequent/combo uses; documentation of prior lenalidomide is required when specified by indication
Proteasome inhibitors (e.g., bortezomib, carfilzomib, ixazomib)	Prior exposure required for many subsequent/combo uses; monotherapy reserved until after ≥3 prior lines including a proteasome inhibitor and an immunomodulatory agent or double‑refractory status
Pomalidomide	Required prior therapies for certain combination regimens: daratumumab may be used in combination with pomalidomide and dexamethasone after ≥1 prior therapies when criteria met; monotherapy permitted only after ≥3 prior lines including a PI and an IMiD or double‑refractory
Carfilzomib	Included as a listed combination partner for subsequent therapy; prior exposure requirements depend on the specific regimen and line of therapy per criteria
None (monotherapy)	Monotherapy is allowable only after at least 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or if double‑refractory to both classes

Example sequencing note	Policy detail / implication
Prior therapy with lenalidomide and a proteasome inhibitor	Policy states patients should have received at least one prior line including lenalidomide and a PI for certain subsequent uses; prior‑therapy documentation may be required for authorization
Monotherapy sequencing	Daratumumab monotherapy is restricted to patients after ≥3 prior lines including a PI and an immunomodulatory agent or those who are double‑refractory to those classes
Use in combination regimens for subsequent therapy	Policy incorporates combinations with agents such as carfilzomib, pomalidomide, and Xpovio for subsequent therapy per NCCN updates; sequencing depends on prior lines and agents received

Quantity Limits and Dosing Schedule

Daratumumab / Daratumumab-hyaluronidase-fihj — Dosing schedules

IV dosing schedule (typical)16 mg/kg IV: induction weekly (Weeks 1–6), then every 3 weeks (Weeks 7–24) then every 4 weeks until disease progression, with regimen-specific variations per indication

SC dosing schedule (fixed)1,800 mg daratumumab + 30,000 units hyaluronidase SC: initial/induction and maintenance schedules mirror IV frequency adjustments per product labeling (e.g., weekly then every 2 weeks then every 4 weeks)

Maximum dose referenceMaximum doses and regimen-specific tables referenced in the package insert (see dosing tables)

Site of Care and Administration

Note

Administration site and technique

For SC administration, inject the fixed-dose daratumumab/hyaluronidase-fihj into the abdomen over approximately 3 to 5 minutes; IV formulations should be administered in an appropriate infusion setting per product labeling (infusion center).

Definitions

ASCT definition

ASCTAutologous stem cell transplant

Context of useReferenced in induction/consolidation and post‑transplant regimens for multiple myeloma in policy dosing tables

Abbreviation sourceDefined in policy appendices (Appendix A)

MM definition

MMMultiple myeloma

Clinical rolePrimary disease indication for daratumumab-containing regimens across induction, consolidation, and subsequent therapy

Age population

Background

Daratumumab is a CD38‑directed cytolytic monoclonal antibody used primarily to treat multiple myeloma in various lines of therapy. The subcutaneous formulation, daratumumab/hyaluronidase‑fihj (Darzalex Faspro), combines daratumumab with hyaluronidase to enable fixed‑dose subcutaneous administration (providing 1,800 mg daratumumab with 30,000 units hyaluronidase) and is indicated in similar combinations and settings per the product labeling and NCCN compendium.

Revision History

2017-07-01effective_date

Policy CP PHAR.310 became effective.

08.25reviewLatest

Policy underwent review (Last Review Date recorded).

OpenPayer

Daratumumab (Darzalex) and Daratumumab/Hyaluronidase-fihj (Darzalex Faspro) coverage

Coverage Criteria for Daratumumab Products

Initial Therapy Rules

Criteria for Continued Therapy

Provider Actions, Prior Authorization & Documentation

Coding and Dosing References

Step Therapy and Prior Treatments

Quantity Limits and Dosing Schedule

Site of Care and Administration

Definitions

Background

Revision History