ModifiedNeighborhood Health Plan of Rhode IslandPolicy N/A

Revlimid

Defines accepted indications, exclusions, dosing limits, and required evidence sources for coverage of Revlimid (lenalidomide) across malignancies (MM, MDS, NHL, CLL/SLL) for Evolent-managed lines of business (Commercial, Exchange/Marketplace, Medicaid). Includes contraindications, warnings, and a HCPCS/J-code.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyRevlimid

Policy CodePolicy N/A

Change TypeModified (template conversion; added indications & coding)

Effective Date

Next Review Date

Key ActionEnsure medication requests are supported by FDA labeling, CMS compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature per CMS Chapter 15 and submit for Evolent authorization.

SourceLink

POLICY UPDATE CHANGES

Converted to new Evolent guideline template and replaced prior UM ONC_1193 Revlimid policy.

Added MM indication for initial therapy for transplant-ineligible members in combination with isatuximab-irfc + bortezomib +/- steroid (Dec 2024 entry).

Added Evolent disclaimer language and Coding Information section with HCPCS code (Dec 2024).

4Covered tumor types (MM, MDS, NHL, select CLL/SLL conditions)

3Not-supported regimens explicitly listed

Maximum capsules/month

Coverage Summary

This policy defines accepted oncology indications for Revlimid (lenalidomide) across Evolent-managed lines of business and reflects a mixed coverage stance: approved use for multiple myeloma (first-line, subsequent lines, and maintenance), myelodysplastic syndromes (MDS) with symptomatic anemia, selected non-Hodgkin’s lymphoma (relapsed/refractory settings), and constrained use for CLL/SLL (not supported when lenalidomide +/- rituximab due to lack of Level 1 evidence). Coverage requires supporting evidence from FDA labeling, CMS compendia, NCCN, ASCO guidelines, or peer-reviewed literature meeting CMS Chapter 15 standards. The policy enforces dosing limits by indication with single-dose maximums of 20 mg for FL/MZL, 10 mg for MDS, and 25 mg for MM/DLBCL/MCL, and a maximum of 21 capsules per month for strengths 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg. Evolent processes authorizations and may deny reimbursement for uses not supported by the required evidence.

Key thresholds and quick facts

Single dose limits by indication20 mg (Follicular/MZL); 10 mg (MDS); 25 mg (MM/DLBCL/MCL)

Maximum capsules per month21 capsules/month for strengths 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg

Coverage - tumor types (count)4 covered tumor types (MM, MDS, NHL, select CLL/SLL conditions)

Not-supported regimens (count)3 explicitly listed not-supported regimens/settings

Initial Therapy Criteria

Multiple Myeloma (MM) - Initial / First Line Therapy

Revlimid (lenalidomide) may be used for members with multiple myeloma in the following first-line combinations:

ANY of the following

In combination with bortezomib with or without steroid
In combination with daratumumab plus bortezomib with or without steroid (for transplant-eligible members only)
In combination with daratumumab with or without steroid (for transplant-ineligible members)
In combination with isatuximab-irfc plus bortezomib with or without steroid (for transplant-ineligible members)

Continuation Therapy Criteria

Continuation request exemption (for not-approvable medication)

Continuation requests shall be exempt from this policy if ALL of the following are met:

The member has not experienced disease progression on the requested medication.

The requested medication was used within the last year without a lapse of more than 30 days of having an active authorization.

Additional medication(s) are not being added to the continuation request.

Denial Risk

Continuation exemption constraints

Contraindications and Warnings

Absolute contraindications and key warnings:

Contraindication: Pregnancy.

Contraindication: Severe hypersensitivity to lenalidomide.

Warning: Lenalidomide can cause significant neutropenia and thrombocytopenia; may require dose interruption, reduction, blood product support, and/or growth factors.

Warning: Increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke (noted in MM patients treated with lenalidomide + dexamethasone); monitor and counsel for thromboembolism signs/symptoms.

Exclusions and Not Supported Uses

Exclusion Criteria

Therapies or situations in which coverage is excluded:

Member has disease progression while taking Revlimid (lenalidomide).

Dosing exceeds single dose limit of Revlimid (lenalidomide): 20 mg for FL/MZL, 10 mg for MDS, or 25 mg for MM/DLBCL/MCL.

Treatment exceeds the maximum limit of 21 capsules/month for strengths: 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, or 25 mg.

Investigational use or off-label indication that lacks sufficient evidence or is not generally accepted by the medical community per policy criteria.

Applicable Codes

Drug J-codeHCPCS

J8999

lenalidomide

Provider Actions & Prior Authorization

Prior Authorization

Evolent authorization required

Evolent is responsible for processing medication requests; medications not authorized by Evolent may be deemed not approvable and not reimbursable.

J8999

Documentation Required

Support with recognized evidence

Medication use must be supported by FDA labeling, CMS-approved compendia, NCCN, ASCO clinical guidelines, or acceptable peer-reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 requirements.

Clinical Evidence & References

Key evidence sources cited in the policy include trials and guideline sources such as GRIFFIN, IMROZ, PERSEUS, POLLUX, CASTOR, ECHELON-3, and standard references (Revlimid prescribing information, Clinical Pharmacology, Micromedex, and NCCN 2025). The policy notes that some uses require Level 1 Evidence, defined as randomized clinical trials and/or meta-analyses demonstrating superior outcomes.

Background

Background: This guideline defines accepted oncology indications for lenalidomide including FDA-approved and select off-label uses supported by compendia and guideline evidence. Evolent is responsible for processing medication requests and may deny reimbursement when use is not supported by the required evidence sources; the document was converted to a new Evolent guideline template and updated with new indications and references in December 2024 and March 2025.

Definitions

Continuation exemptionAn exemption allowing continuation of a previously authorized medication that is not otherwise approvable if all are met: no disease progression on the medication; medication used within the last year without >30-day lapse of active authorization; and no additional medications are being added.

Level 1 EvidenceRandomized clinical trial and/or meta-analyses demonstrating superior outcomes.

Revision History

March 2025template_conversionLatest

Converted to new Evolent guideline template and replaced prior UM ONC_1193 Revlimid policy; added new indication(s) and updated references.

December 2024added_indication

Added MM indication for initial therapy for transplant-ineligible members in combination with isatuximab-irfc + bortezomib +/- steroid; updated single dose limits in exclusion criteria; added Evolent disclaimer language and Coding Information section with HCPCS code.

December 2024coding_added

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyRevlimid

Policy CodePolicy N/A

Change TypeModified (template conversion; added indications & coding)

Effective Date

Next Review Date

SourceLink

On This Page

In combination with cyclophosphamide with or without steroid

NOT SUPPORTED: Daratumumab + carfilzomib + lenalidomide with or without dexamethasone for initial therapy of newly diagnosed multiple myeloma

Myelodysplastic Syndrome (MDS)

Revlimid (lenalidomide) may be used when ALL of the following apply:

ALL of the following

Genetic subtype (ONE of)
- del(5q) chromosomal abnormality
- No del(5q) chromosomal abnormality
Member has very low, low, or intermediate risk MDS associated with symptomatic anemia

Non-Hodgkin's Lymphoma (NHL)

Revlimid (lenalidomide) may be used for the following Non-Hodgkin's Lymphoma (NHL) indications and contains specific allowed combinations; the Not supported regimens/settings are listed below.

ALL of the following

Member has Non-Hodgkin's Lymphoma (including Follicular Lymphoma, Nodal Marginal Zone Lymphoma, Mantle Cell Lymphoma, and Splenic Marginal Zone Lymphoma) AND lenalidomide is being used for relapsed or refractory disease as second-line or subsequent therapy, with or without rituximab/rituximab biosimilar
Revlimid may be used in combination with brentuximab vedotin (Adcetris) and rituximab/rituximab biosimilar for adult members with relapsed or refractory large B-cell lymphoma (LBCL), including DLBCL NOS, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are ineligible for autologous HSCT or CAR T-cell therapy
Not supported regimens / settings
- DLBCL maintenance: single agent lenalidomide
- Marginal Zone Lymphomas (MZL), initial therapy: lenalidomide + rituximab
- Mantle Cell Lymphoma (MCL), second line and subsequent therapy: ibrutinib + lenalidomide + rituximab

General coverage preamble / evidence requirement

Required evidence sources for coverage determinations include the FDA product labeling, CMS-approved compendia, NCCN and ASCO clinical guidelines, and peer-reviewed literature consistent with CMS Medicare Benefit Policy Manual Chapter 15.

ANY of the following

FDA-approved product labeling
CMS-approved compendia
National Comprehensive Cancer Network (NCCN) guidelines
American Society of Clinical Oncology (ASCO) clinical guidelines
Peer-reviewed medical literature meeting CMS Medicare Benefit Policy Manual Chapter 15 requirements

Additional consolidated completeness items

The following indications are consolidated here to ensure completeness: Revlimid is not supported for CLL/SLL as specified; Multiple Myeloma subsequent-line and maintenance uses are allowed as described.

ALL of the following

Lenalidomide with or without rituximab/rituximab biosimilar is NOT supported by this policy for treatment of CLL/SLL due to insufficient Level 1 evidence to demonstrate superior outcomes compared to recommended alternatives.
Multiple Myeloma - Subsequent Line Therapy and Maintenance
- Maintenance therapy as a single agent after completion of therapy for newly diagnosed or relapsed/refractory disease or after completion of autologous stem cell transplant
- For relapsed or refractory disease, lenalidomide may be used as ONE of the following: single agent (with or without dexamethasone); with daratumumab (Darzalex/Darzalex Faspro) with or without dexamethasone; with bortezomib with or without dexamethasone; with ixazomib (Ninlaro) with or without dexamethasone; with carfilzomib (Kyprolis) with or without dexamethasone; with elotuzumab (Empliciti) with or without dexamethasone; with bendamustine with or without dexamethasone; or with cyclophosphamide (Cytoxan) with or without dexamethasone.

Continuation exemption applies only if all three conditions are met; failure to meet these constraints risks denial of continuation requests.

No disease progression on the requested medication.
Requested medication was used within the last year without a lapse of more than 30 days of having an active authorization.
No additional medication(s) are being added to the continuation request.

Billing Rule

Adhere to single-dose and monthly capsule limits

Adhere to the listed single-dose limits by indication and the monthly capsule maximum to avoid exclusions from coverage.

FL/MZL: single-dose limit 20 mg
MDS: single-dose limit 10 mg
MM/DLBCL/MCL: single-dose limit 25 mg
Maximum of 21 capsules per month for strengths 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg

Billing Rule

Adhere to single-dose and monthly capsule limits

Claims exceeding authorization or dose/capsule limits may be excluded from coverage and denied.

Exclusions apply for dosing that exceeds single-dose limits by indication (20 mg for FL/MZL; 10 mg for MDS; 25 mg for MM/DLBCL/MCL).
Exclusions apply when treatment exceeds the maximum of 21 capsules per month for the listed strengths.

Added Coding Information section with HCPCS code J8999 (lenalidomide) and updated coding and standards.