CurrentHealth NetPolicy CP PHAR.309

Clinical Policy: Carfilzomib (Kyprolis)

Clinical coverage policy for carfilzomib (Kyprolis) governing medical necessity criteria, approved and off-label indications (multiple myeloma, Waldenstrom's macroglobulinemia, systemic light-chain amyloidosis), dosing guidance, approval durations, prescriber and documentation requirements, and HCPCS coding implications for Commercial, HIM and Medicaid lines of business.

Policy Summary

PayerHealth Net

PolicyClinical Policy: Carfilzomib (Kyprolis)

Policy CodePolicy CP PHAR.309

Change TypeAnnual review updates (2020, 2022, 2023, 2024)

Effective DateFeb 1, 2017

Next Review Date

Key ActionProvider must submit chart notes, lab results, or other clinical information supporting diagnosis, measurable disease, IMWG-defined progressive disease, and regimen choice.

SourceLink

POLICY UPDATE CHANGES

4Q 2023 annual review: updated MM initial approval criteria to include maintenance therapy with lenalidomide and added bendamustine + dexamethasone option for late relapse; removed panobinostat regimens.

4Q 2022 annual review: added new indication combinations with Sarclisa and Darzalex Faspro for MM after 1–3 lines and added criteria for systemic light chain amyloidosis.

4Q 2020 annual review: added MM FDA-approved regimen in combination with daratumumab and NCCN-recommended regimen with dexamethasone + cyclophosphamide + thalidomide.

3Covered Indications (including off-label sets)

Typical initial approval duration

J9047Primary HCPCS code referenced

Coverage Summary & Scope

Scope: Clinical coverage policy for carfilzomib (Kyprolis) governing medical necessity criteria, approved and off-label indications (multiple myeloma, Waldenstrom's macroglobulinemia, systemic light-chain amyloidosis), dosing guidance, approval durations, prescriber and documentation requirements, and HCPCS coding implications for Commercial, HIM, and Medicaid lines of business.

Coverage stance: Kyprolis is covered with criteria when the medical necessity criteria are met (see policy criteria for diagnosis, prescriber, age, measurable disease/progression, permitted regimens, dosing limits, and documentation).

Background: Carfilzomib (Kyprolis) is a proteasome inhibitor approved for relapsed or refractory multiple myeloma and used in various combination regimens; the policy aligns coverage with FDA approvals and NCCN recommendations and includes select off-label indications Waldenstrom's macroglobulinemia (WM/LPL) and systemic light-chain (AL) amyloidosis when criteria are met.

Typical initial approval duration: 6 months (policy specifies Medicaid/HIM = 6 months; Commercial = 6 months or to the member's renewal date, whichever is longer).

Key thresholds and dates

Serum M-protein threshold≥ 0.5 g/dL

Urine M-protein threshold≥ 200 mg/24 h

Serum involved FLC threshold≥ 100 mg/L (10 mg/dL) with abnormal FLC ratio

IMWG progressive disease — Serum M-component increaseAbsolute increase ≥ 0.5 g/dL

IMWG progressive disease — Urine M-component increaseAbsolute increase ≥ 200 mg/24 h

IMWG progressive disease — FLC increase> 10 mg/dL (absolute increase)

Effective date02.01.17

Last review / P&T approval date11.24 (P&T Approval Date = 11.24)

Initial Approval Criteria - Multiple Myeloma (MM)

Kyprolis is medically necessary when ALL of the following are met:

ALL of the following

ALL of the following
- Diagnosis of multiple myeloma (MM).
- Prescribed by or in consultation with an oncologist or hematologist.
- Age ≥ 18 years.
Disease status (one of)

Initial Approval Criteria - Waldenstrom's Macroglobulinemia (WM/LPL) (off-label)

Kyprolis may be medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of Waldenstrom's macroglobulinemia (lymphoplasmacytic lymphoma).
Prescribed by or in consultation with an oncologist.
Age ≥ 18 years.
Regimen: Prescribed as a component of CaRD (carfilzomib, rituximab, dexamethasone) regimen as primary or Kyprolis‑relapsed therapy.
CaRD regimen requirement

Initial Approval Criteria - Systemic Light Chain (AL) Amyloidosis (off-label)

Initial Approval Criteria - Systemic Light Chain Amyloidosis (off-label)

Kyprolis may be medically necessary 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.
Age ≥ 18 years.
Disease setting (one of)
- Newly diagnosed disease.

Other Diagnoses / Indications

Other diagnoses/indications

For other uses not covered above, follow formulary/non‑formulary/off‑label policies:

ANY of the following

Formulary/PDL: If drug is on formulary/PDL, refer to no‑coverage criteria policy for relevant line of business: CP.CPA.190 (commercial), HIM.PA.33 (marketplace), CP.PMN.255 (Medicaid).
Non‑formulary: If drug is NOT on formulary/PDL, refer to non‑formulary policy: CP.CPA.190 (commercial), HIM.PA.103 (marketplace), CP.PMN.16 (Medicaid).
Off‑label policy: If requested use is not specifically listed and criterion above does not apply, refer to off‑label use policy: CP.CPA.09 (commercial), HIM.PA.154 (marketplace), CP.PMN.53 (Medicaid).

Continued Therapy / Renewal Criteria

Continued Therapy (All Indications)

Renewal/continued therapy is authorized when ALL of the following are met:

ALL of the following

Current therapy or prior exposure: Member is currently receiving Kyprolis via Centene benefit OR documentation supports member has received Kyprolis for a covered indication for at least 30 days.≥ 30 days or currently on benefit
Response: Member is responding positively to therapy.
Clinical response required
Dose limits for continued therapy (depending on regimen)

Provider Actions & Billing Requirements

Prior Authorization

Prior authorization may be required

Prior authorization may be required for Kyprolis. Prescribers should obtain PA per payer processes before initiating therapy.

Documentation Required

Submit clinical documentation

Provider must submit chart notes, lab results, or other clinical information supporting diagnosis, measurable disease (within specified timeframes), progressive disease per IMWG, and the chosen regimen.

Measurable disease assessed within the last 30 days: Serum M‑protein ≥ 0.5 g/dL; Urine M‑protein ≥ 200 mg/24 h; or involved serum FLC ≥ 100 mg/L (10 mg/dL) with abnormal FLC ratio (see criteria).
IMWG progressive disease evidence assessed within 60 days following last dose of prior antimyeloma regimen (IMWG PD thresholds include serum M‑component absolute increase ≥ 0.5 g/dL; urine M‑component absolute increase ≥ 200 mg/24 h; FLC absolute increase > 10 mg/dL).

Applicable Codes

Relevant HCPCS Billing CodeHCPCS

J9047

Injection, carfilzomib; 1 mg

Clinical Evidence & References

References: NCCN compendium/guidelines referenced include NCCN Multiple Myeloma v04.2024, Waldenstrom's (WM) v02.2024, and Systemic Light Chain Amyloidosis v02.2024.

Additional reference: Kyprolis Prescribing Information (Accessed July 15, 2024).

Carfilzomib (Kyprolis) is a proteasome inhibitor indicated for adult patients with relapsed or refractory multiple myeloma and is used in various combination regimens and as monotherapy per FDA labeling and NCCN guidance.

This policy aligns coverage with FDA approvals and NCCN recommendations and includes select off-label indications (Waldenstrom's macroglobulinemia and systemic light-chain amyloidosis) when applicable criteria and supporting evidence are provided.

The prescribing information and policy appendices provide detailed dosing and administration schedules for approved regimens (including twice-weekly 20/56 mg/m2 and once-weekly 20/70 mg/m2 escalation regimens) and specify that off-label dosing must be supported by practice guidelines or peer-reviewed literature.

Definitions

Definitions: CaRD — carfilzomib, rituximab, and dexamethasone.

FLC — free light chain.

IMWG — International Myeloma Working Group.

NCCN — National Comprehensive Cancer Network.

Revision History

11.24addedLatest

4Q 2024 annual review: added hematologist as prescriber option and IMWG criterion defining progressive MM disease; added regimens including combination with Xpovio, cyclophosphamide, pomalidomide, and venetoclax for t(11;14); added systemic AL amyloidosis treatment options for newly diagnosed or relapsed disease. Also revised Commercial approval duration language to '6 months or to the member's renewal date, whichever is longer'. P&T Approval Date = 11.24.

11.23revised

Policy Summary

PayerHealth Net

PolicyClinical Policy: Carfilzomib (Kyprolis)

Policy CodePolicy CP PHAR.309

Change TypeAnnual review updates (2020, 2022, 2023, 2024)

Effective DateFeb 1, 2017

Next Review Date

Key ActionProvider must submit chart notes, lab results, or other clinical information supporting diagnosis, measurable disease, IMWG-defined progressive disease, and regimen choice.

SourceLink

On This Page

Measurable disease assessed within the last 30 days evidenced by at least ONE of: Serum M-protein ≥ 0.5 g/dL; Urine M-protein ≥ 200 mg/24 h; Serum free light chain (FLC) assay: involved FLC level ≥ 100 mg/L (10 mg/dL) provided serum FLC ratio is abnormal.Serum M-protein ≥ 0.5 g/dL; Urine M-protein ≥ 200 mg/24 h; Serum involved FLC ≥ 100 mg/L with abnormal ratio

Supports measurable disease criteria (assessed within 30 days)

Progressive disease as defined by IMWG response criteria, assessed within 60 days following the last dose of the last antimyeloma regimen received.IMWG progressive disease per Appendix D

IMWG PD criteria examples include serum M-component absolute increase ≥ 0.5 g/dL, urine M-component ≥ 200 mg/24 h, or FLC absolute increase > 10 mg/dL.

Permitted regimen context (one of primary, maintenance, or previously treated)

Primary therapy: Kyprolis prescribed in combination with one of the following: dexamethasone + lenalidomide; dexamethasone + cyclophosphamide; dexamethasone + lenalidomide + daratumumab (Darzalex).
Primary therapy options per policy
Maintenance therapy: Kyprolis prescribed in combination with lenalidomide.
Maintenance therapy option
Previously treated (relapsed or refractory): Kyprolis prescribed as one of the following regimen options: monotherapy; with dexamethasone; with lenalidomide + dexamethasone (for patients who have received 1–3 lines of therapy); with daratumumab (Darzalex) or Darzalex Faspro + dexamethasone (1–3 lines); with isatuximab (Sarclisa) + dexamethasone (1–3 lines); with selinexor (Xpovio) + dexamethasone (1–3 lines); with pomalidomide + dexamethasone (1–3 lines); with dexamethasone + cyclophosphamide ± thalidomide (1–3 lines); with venetoclax + dexamethasone in patients with t(11;14) translocation (1–3 lines); with bendamustine + dexamethasone for late relapse/progressive disease in patients who have failed ≥3 therapies; other NCCN‑recommended combinations.
Previously treated regimen options per policy

Dose limits (must meet applicable limit depending on regimen)

Monotherapy: dose does not exceed 56 mg/m2 twice weekly each 28‑day cycle.≤ 56 mg/m2 twice weekly
Monotherapy dose limit
With dexamethasone + lenalidomide: dose does not exceed 27 mg/m2 twice weekly 3 out of 4 weeks for twelve 28‑day cycles, then 27 mg/m2 twice weekly 2 out of 4 weeks for next six 28‑day cycles (up to total of 18 cycles).27 mg/m2 twice weekly per cycle schedule
Twice‑weekly 20/27 regimen limits and duration
Once‑weekly regimen: 70 mg/m2 once weekly each 28‑day cycle.70 mg/m2 once weekly
Once‑weekly dose limit
With dexamethasone + isatuximab (Sarclisa): 56 mg/m2 twice weekly each 28‑day cycle.56 mg/m2 twice weekly
Sarclisa combination dose limit
Off‑label dosing evidence: Dose for off‑label regimens must be supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.Supporting evidence required
Off‑label use requirement per policy

Provider/documentation: Provider must submit documentation (chart notes, labs, etc.) supporting that member meets all approval criteria.

Documentation requirement per policy

Prior authorization may be required.

PA note per policy

Evidence for off‑label dosing: Dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.Supporting evidence required

Off‑label evidence requirement

Prior authorization may be required.

PA note per policy

Relapsed/refractory disease (including repeat of initial therapy if relapse‑free for several years).

Permitted regimen

Kyprolis as a single agent.
Kyprolis in combination with dexamethasone.

Off‑label evidence: Dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.Supporting evidence required

Off‑label use requirement

Monotherapy: new dose does not exceed 56 mg/m2 twice weekly each 28‑day cycle.≤ 56 mg/m2 twice weekly

With dexamethasone + lenalidomide: new dose does not exceed 27 mg/m2 twice weekly 3 out of 4 weeks for twelve 28‑day cycles, then 27 mg/m2 twice weekly 2 out of 4 weeks for next six 28‑day cycles (up to 18 cycles).27 mg/m2 per schedule

Once‑weekly: 70 mg/m2 once weekly each 28‑day cycle.70 mg/m2 once weekly

With dexamethasone + daratumumab: new dose does not exceed 56 mg/m2 twice weekly each 28‑day cycle.56 mg/m2 twice weekly

With dexamethasone + isatuximab (Sarclisa): 56 mg/m2 twice weekly each 28‑day cycle.56 mg/m2 twice weekly

Off‑label dosing evidence: New dose for off‑label uses must be supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.Supporting evidence required

Continued Therapy - WM and AL amyloidosis (off-label)

Renewal criteria (must meet all):

ALL of the following

Current therapy or prior exposure: Member currently receiving medication via Centene benefit OR documentation supports member has received Kyprolis for a covered indication for at least 30 days.≥ 30 days or currently on benefit
Response: Member is responding positively to therapy.
Off‑label dose evidence: New dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.Supporting evidence required

Relevant labs and chart notes demonstrating response/eligibility and regimen rationale.

Documentation Required

Support off-label dosing with evidence

For off‑label uses or dosing, the prescriber must submit supporting evidence from practice guidelines or peer‑reviewed literature showing the dose/regimen is supported; prescribed regimen must be FDA‑approved or NCCN‑recommended.

Billing Rule

Use HCPCS J9047 for claims

Report carfilzomib on medical claims using HCPCS code J9047 per coding guidance.

J9047 — Injection, carfilzomib; 1 mg

4Q 2022 annual review: added new indication combinations with Sarclisa and Darzalex Faspro for MM after 1–3 lines and added criteria for systemic light chain amyloidosis. References reviewed and P&T Approval Date = 11.22.

11.20added

4Q 2020 annual review: added MM FDA-approved regimen in combination with daratumumab and NCCN-recommended regimen with dexamethasone + cyclophosphamide + thalidomide. References reviewed and P&T Approval Date = 11.20.