Centene daratumumab Coverage Update: Prior Auth

Coverage Criteria for Daratumumab Products

Initial Approval — Multiple Myeloma

Covered when ALL of the following are met:

ALL of the following

Diagnosis of multiple myeloma (MM).
Prescribed by or in consultation with an oncologist or hematologist.
Age >= 18 years.
Daratumumab/Darzalex Faspro prescribed as one of the following:
- Primary therapy
  - Ineligible for ASCT
    In combination with lenalidomide and dexamethasone.
    In combination with bortezomib, melphalan, and prednisone.
    In combination with bortezomib, lenalidomide, and dexamethasone.
  - Eligible for ASCT
    In combination with bortezomib, thalidomide, and dexamethasone.
    In combination with bortezomib, lenalidomide, and dexamethasone.
    In combination with bortezomib, cyclophosphamide, and dexamethasone.
    In combination with carfilzomib, lenalidomide, and dexamethasone.
  - High-risk smoldering MM monotherapy
    Used as monotherapy for high-risk smoldering MM.
    Member meets at least two of the following: serum monoclonal protein > 2 g/dL; involved-to-uninvolved serum-free light chain ratio > 20; bone marrow plasma cells > 20%.
- Subsequent therapy
  - In combination with dexamethasone and either lenalidomide, bortezomib (with or without cyclophosphamide), carfilzomib, venetoclax (Venclexta), or selinexor (Xpovio) after >= 1 prior therapy.
  - In combination with carfilzomib, pomalidomide, and dexamethasone.
  - In combination with pomalidomide and dexamethasone after >= 1 prior therapies including both an immunomodulatory agent (e.g., thalidomide, lenalidomide) and a proteasome inhibitor (e.g., ixazomib, bortezomib, carfilzomib).
  - As monotherapy after >= 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or for patients who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
- Maintenance therapy (off-label)
  - As a single agent for symptomatic MM as maintenance therapy.
  - In combination with lenalidomide for transplant candidates (off-label).
If applicable, prescribed regimen must be FDA-approved or recommended by NCCN; if dose exceeds FDA-indicated maximum, prescriber must submit supporting practice guideline or peer-reviewed literature evidence.
Prior authorization may be required.

Initial Approval — Systemic Light Chain (AL) Amyloidosis

Covered when ALL of the following are met:

ALL of the following

Diagnosis of systemic light chain (AL) amyloidosis.
Prescribed by or in consultation with an oncologist or hematologist.
Age >= 18 years.
Daratumumab/Darzalex Faspro prescribed as one of the following:
- In combination with bortezomib, cyclophosphamide, and dexamethasone (VCd).
- In combination with lenalidomide and dexamethasone.

Initial Approval — T-cell Acute Lymphoblastic Leukemia (Off-label)

Covered when ALL of the following are met:

ALL of the following

Diagnosis of T-cell acute lymphoblastic leukemia (T-ALL).
Prescribed by or in consultation with an oncologist or hematologist.
Member has relapsed or refractory disease.
Prescribed as part of a daratumumab-containing regimen (for example daratumumab plus vincristine, pegaspargase or calaspargase, doxorubicin, and prednisone or dexamethasone).
Dose is within the FDA maximum limit for any FDA-approved indication in Section V or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use; prescriber must submit supporting evidence when requested.

Coverage overview and notable criteria history

Covered when ALL of the following are met:

ALL of the following

Member is currently receiving medication via the Centene benefit, or documentation supports that member has received daratumumab or Darzalex Faspro for a covered indication for at least 30 days.
Member is responding positively to therapy (e.g., clinical benefit or disease stability as documented by the prescriber).
Dose changes
- If request is for a dose increase, new dose does not exceed the maximum indicated regimen in Section V.
- If request is for a dose increase, new dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

Coding and Dosing

HCPCS Codes referencedHCPCS

J9144	Injection, daratumumab, 10 mg and hyaluronidase-fihj
J9145	Injection, daratumumab, 10 mg

Fixed-dose SC and weight‑based IV doses — key dosing

Darzalex Faspro (subcutaneous)1,800 mg daratumumab + 30,000 units hyaluronidase SC (administered into the abdomen over ~3–5 minutes); dosing schedule: Weeks 1–8 weekly, Weeks 9–24 every 2 weeks, Weeks 25+ every 4 weeks until disease progression.

Daratumumab (intravenous)16 mg/kg IV; example MM schedule: Weeks 1–8 weekly, Weeks 9–24 every 2 weeks, Weeks 25+ every 4 weeks until disease progression.

Daratumumab IV (alternate regimen with VMP)16 mg/kg IV: Weeks 1–6 weekly, Weeks 7–54 every 3 weeks, Weeks 55+ every 4 weeks until disease progression.

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization and Prescriber Requirements

Prior Authorization Required: Daratumumab (Darzalex) and Darzalex Faspro require prior authorization. Prescriptions must be written by or in consultation with an oncologist or hematologist. Approval durations vary by line of business: Medicaid/HIM — up to 12 months; Commercial — 6 months or to the member’s renewal date, whichever is longer. Providers should allow time for PA review and include requested supporting documentation.

Prior authorization may be required for specific regimens and lines of therapy.
Prescriber specialty requirement: oncologist or hematologist.

Documentation Required

Supporting Clinical Documentation

Supportive Documentation Required: Providers must submit clinical documentation demonstrating the member meets all approval criteria. Acceptable documentation includes office chart notes, relevant laboratory results, imaging reports, pathology, prior treatment records showing lines of therapy, and consult notes when applicable.

Covered Regimens and Dosing Schedules

Regimen	Setting / Indication-level notes
Daratumumab + lenalidomide + dexamethasone (D-Rd)
Induction/consolidation or subsequent therapy: FDA‑approved for newly diagnosed patients ineligible for ASCT and for relapsed/refractory MM after ≥1 prior therapy; dosing: IV 16 mg/kg weekly (weeks 1–8), q2w (weeks 9–24), then q4w; SC Faspro 1,800 mg weekly→q2w→q4w where indicated.
Daratumumab + bortezomib + melphalan + prednisone (D-VMP)
Primary therapy for newly diagnosed patients ineligible for ASCT: FDA‑approved (VMP regimen); IV dosing weekly (weeks 1–6) then q3w (weeks 7–54) then q4w; Faspro SC follows same timing with fixed 1,800 mg dose per PI.
Daratumumab + bortezomib + lenalidomide + dexamethasone (D‑VRd)
Induction/consolidation for newly diagnosed patients (eligible or ineligible for ASCT) per Faspro approval; SC Faspro schedule: weekly during induction then q3w/q2w per ASCT eligibility and continue q4w until progression.
Daratumumab + bortezomib + thalidomide + dexamethasone (D‑VTd)
Induction for patients eligible for ASCT: FDA‑approved combination; IV and SC schedules include weekly then q2w consolidation per prescribing information.
Daratumumab + bortezomib + cyclophosphamide + dexamethasone (D‑VCd)
Induction for ASCT‑eligible patients (one listed primary option); also used in AL amyloidosis (see AL table). Schedule per product PI; Faspro SC weekly→q2w→q4w as indicated.
Daratumumab + carfilzomib + dexamethasone (D‑Kd)
Relapsed/refractory MM: FDA‑approved for patients with 1–3 prior lines; dosing follows 4‑week cycle (IV 16 mg/kg schedule) or Faspro fixed SC schedule when authorized.
Daratumumab + pomalidomide + dexamethasone (D‑Pd)
Approved for patients who received ≥2 prior therapies including lenalidomide and a PI (Darzalex IV) or for Faspro in patients with ≥1 prior line including lenalidomide and a PI; use per line-of-therapy criteria.
Daratumumab monotherapy
Monotherapy allowable only after ≥3 prior lines including a PI and an immunomodulatory agent or for double‑refractory disease; high‑risk smoldering MM monotherapy allowed per criteria (Faspro approval for smoldering MM).

Regimen	Indication-level notes / restrictions
Daratumumab + bortezomib + cyclophosphamide + dexamethasone (D‑VCd)
Covered for systemic AL amyloidosis in combination for newly diagnosed adult patients per policy; Darzalex Faspro indicated for D‑VCd. Limitation: Faspro not recommended for patients with NYHA Class IIIB/IV cardiac disease or Mayo Stage IIIB outside clinical trials.
Daratumumab + lenalidomide + dexamethasone (D‑Rd)
Permitted combination for AL amyloidosis per policy (listed option); off‑label uses require NCCN dosing and supporting evidence; prescriber must provide supporting documentation for off‑label dosing.
Daratumumab single‑agent
Single‑agent use allowed for relapsed/refractory AL amyloidosis after ≥1 prior therapy (off‑label) or for newly diagnosed patients with significant neuropathy or Mayo stage IIIb (off‑label); off‑label requests must follow NCCN dosing and provide supporting evidence. Exclude patients with advanced cardiac disease (NYHA IIIB/IV or Mayo Stage IIIB) per limitation.

Product / Dose	Dosing schedule (induction / consolidation / maintenance / monotherapy)
IV Daratumumab — 16 mg/kg
Lenalidomide or pomalidomide combinations (4‑week cycle): Weeks 1–8: 16 mg/kg IV weekly; Weeks 9–24: 16 mg/kg IV every 2 weeks; Weeks 25 onward until progression: 16 mg/kg IV every 4 weeks. (Also used for monotherapy with same schedule for later‑line monotherapy).
IV Daratumumab — 16 mg/kg
Bortezomib + melphalan + prednisone (VMP; 6‑week cycle): Weeks 1–6: 16 mg/kg IV weekly; Weeks 7–54: 16 mg/kg IV every 3 weeks; Weeks 55 onward until progression: 16 mg/kg IV every 4 weeks.
IV Daratumumab — 16 mg/kg
Bortezomib + dexamethasone (3‑week cycle): Weeks 1–9: 16 mg/kg IV weekly; Weeks 10–24: 16 mg/kg IV every 3 weeks; Weeks 25 onward until progression: 16 mg/kg IV every 4 weeks. For VTd regimen: induction Weeks 1–8 weekly then Weeks 9–16 q2w; consolidation Weeks 1–8 q2w.
IV Daratumumab — 16 mg/kg
Carfilzomib + dexamethasone (4‑week cycle): Week 1: 8 mg/kg IV days 1 and 2; Weeks 2–8: 16 mg/kg IV weekly; Weeks 9–24: 16 mg/kg IV every 2 weeks; Weeks 25 onward: 16 mg/kg IV every 4 weeks.
SC Darzalex Faspro — 1,800 mg daratumumab + 30,000 units hyaluronidase
Lenalidomide or pomalidomide combinations (4‑week cycle) or monotherapy: Administer SC into abdomen over ~3–5 minutes. Weeks 1–8: weekly; Weeks 9–24: every 2 weeks; Weeks 25 onward until progression: every 4 weeks. Same weekly→q2w→q4w rhythm applies across listed combinations when Faspro is authorized.
SC Darzalex Faspro — 1,800 mg daratumumab + 30,000 units hyaluronidase
VMP (6‑week cycle): Weeks 1–6: weekly; Weeks 7–54: every 3 weeks; Weeks 55 onward: every 4 weeks. VTd and VRd schedules mirror IV timing for induction/consolidation (weekly during induction then q2w or q3w as specified; continue q4w thereafter).
SC Darzalex Faspro — 1,800 mg daratumumab + 30,000 units hyaluronidase
High‑risk smoldering MM (Faspro): Weeks 1–8: weekly (total 8 doses); Weeks 9–24: every 2 weeks (total 8 doses); Weeks 25 onward until diagnosis of MM or max of 3 years per product labeling.

Combination / Note	Schedule (weeks)
Darzalex Faspro + bortezomib + cyclophosphamide + dexamethasone (D‑VCd)
Induction: Weeks 1–8 — SC Faspro 1,800 mg weekly (total of 8 doses); Intermediate: Weeks 9–24 — every 2 weeks (total of 8 doses); Maintenance/continued therapy: Weeks 25 onward — every 4 weeks until disease progression or a maximum of 2 years for AL amyloidosis.
NCCN‑supported additions: Darzalex (IV or Faspro) in combination with lenalidomide + dexamethasone for AL amyloidosis
NCCN guidance supports use of daratumumab with lenalidomide/dexamethasone for AL amyloidosis; off‑label combinations should follow NCCN dosing recommendations and require supporting evidence per policy.

Background and Appendices

Daratumumab is a CD38-directed cytolytic antibody that targets CD38-expressing plasma cells. Daratumumab/hyaluronidase-fihj (Darzalex Faspro) combines daratumumab with recombinant hyaluronidase to permit fixed-dose subcutaneous administration of the agent for treatment of multiple myeloma and selected indications.

Both IV daratumumab and subcutaneous Darzalex Faspro are approved for multiple myeloma in specified combinations and lines of therapy; dosing differs by formulation (IV daratumumab is weight‑based at 16 mg/kg per prescribing regimens while Darzalex Faspro is administered as a fixed 1,800 mg subcutaneous dose with hyaluronidase).

ASCT — abbreviation

ASCT (abbreviation)Autologous stem cell transplant (see Appendix A)

ContextListed in Appendix A: ASCT = autologous stem cell transplant.

Use in policyASCT referenced in eligibility/line-of-therapy criteria for transplant-eligible patients.

ASCT — definition

OpenPayer

Clinical Policy: Daratumumab (Darzalex), Daratumumab/Hyaluronidase-fihj (Darzalex Faspro)

Coverage Criteria for Daratumumab Products

Coding and Dosing

Provider Actions, Prior Authorization, and Documentation

Covered Regimens and Dosing Schedules

Background and Appendices