Neighborhood Health Plan RI venetoclax Coverage

Coverage Criteria for Venetoclax (Venclexta)

Acute Myeloid Leukemia (AML)

Covered when ANY of the following AML indications are met:

AML indications: 1) Combination of venetoclax with decitabine (Dacogen), azacitidine (Vidaza), or low‑dose cytarabine for members with AML who have unfavorable‑risk cytogenetics or who are unsuitable for or decline intensive remission induction therapy (may be used for remission induction and post‑remission therapy). OR 2) The same venetoclax combinations for relapsed/refractory AML.

Supports use for remission induction, post‑remission therapy, and relapsed/refractory disease per policy.

Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Covered when ANY of the following CLL/SLL indications are met:

CLL/SLL indications: Venetoclax in combination with obinutuzumab (Gazyva) as first‑ or subsequent‑line therapy; OR venetoclax as a single agent with or without obinutuzumab (Gazyva), rituximab, or a rituximab biosimilar as subsequent‑line therapy for CLL/SLL.

Specifies first‑line coverage only when given with obinutuzumab; single‑agent use allowed in later lines.

Not Supported Combination Regimens

Not supported regimens due to insufficient Level 1 evidence:

Unsupported ALL regimens: Venetoclax combined with chemotherapy regimens (e.g., decitabine, hyper‑CVAD, nelarabine, mini‑hyper‑CVD) is not supported for relapsed/refractory acute lymphoblastic leukemia (ALL) due to lack of Level 1 evidence.

Position based on absence of randomized trials or meta‑analyses showing superiority compared to Evolent recommended regimens.

Unsupported Mantle Cell regimens: Venetoclax ± rituximab and venetoclax + ibrutinib (Imbruvica) regimens are not supported for mantle cell lymphoma because Level 1 evidence is lacking.

Providers should follow Evolent recommended agents/regimens (Evolent Pathways).

Exclusions to coverage for venetoclax include clinical or administrative circumstances where safety, dosing, duration, or evidence thresholds are not met. Specifically, requests will be excluded for disease progression while taking venetoclax; if the prescribed dosing exceeds the single-dose limit of 400 mg; or if monthly quantity limits are exceeded — i.e., more than 120 tablets (100 mg), 120 tablets (50 mg), or 15 tablets (10 mg) per month. Treatment duration limits must also be respected: venetoclax used with obinutuzumab (Gazyva) is limited to a maximum of 12 months (venetoclax component), while venetoclax with rituximab is limited to a maximum of 2 years.

Additionally, investigational or off‑label uses lacking sufficient supporting evidence are excluded. Sufficient evidence is defined by inclusion in CMS‑recognized compendia or acceptable peer‑reviewed literature that adequately represents the patient and regimen, reports clinically meaningful outcomes (for example, ASCO‑recommended thresholds such as hazard ratio < 0.80 or survival benefit of at least 3 months for OS/PFS), and employs an appropriate study design. Case reports and meeting abstracts without a corresponding full peer‑reviewed article do not provide adequate supportive evidence for coverage.

Certain combination regimens with venetoclax are considered not medically necessary or otherwise not supported by policy because of inadequate Level 1 evidence. Evolent does not support venetoclax combined with chemotherapy regimens for relapsed/refractory acute lymphoblastic leukemia (examples include decitabine, hyper‑CVAD, nelarabine, mini‑hyper‑CVD).

Similarly, venetoclax regimens for mantle cell lymphoma such as venetoclax +/- rituximab or venetoclax + ibrutinib (Imbruvica) are not supported due to the lack of randomized trials or meta‑analyses demonstrating superior outcomes compared to Evolent‑recommended regimens. These uses are classified as investigational/off‑label and are subject to exclusion when sufficient evidence from CMS compendia or peer‑reviewed literature is not available.

Requests for these unsupported combination regimens should be accompanied by high‑quality evidence meeting the policy’s documentation expectations; absent that, such uses will be considered not medically necessary per the policy positions.

Covered Regimens and Supported Combinations

Regimen	Indication / Line of therapy	Coverage status
Venetoclax + decitabine
Patients with AML who have unfavorable-risk cytogenetics or are unsuitable for intensive remission induction therapy or decline intensive therapy; may be used for remission induction, post‑remission therapy, or relapsed/refractory AML
Covered

Regimen	Indication / Line of therapy	Coverage status
Venetoclax + obinutuzumab (Gazyva)
Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) — first‑ or subsequent‑line therapy
Covered

Regimen (examples)	Indication / Rationale	Coverage status
Venetoclax + chemotherapy (e.g., decitabine, hyper‑CVAD, nelarabine, mini‑hyper‑CVD)
Relapsed/refractory acute lymphoblastic leukemia (ALL) — regimens not supported due to lack of Level 1 evidence
Not covered

Billing and Quantity Limits

Drug HCPCS CodesHCPCSCovered

J8999

venetoclax

inv-07: Single dose limit — <= 400 mg

Single dose limit<= 400 mg per single dose

ContextRequests exceeding this single-dose limit are listed as exclusion/denial criteria

Related codeApplies to venetoclax (J8999) billing requests per policy

inv-08: Monthly tablet limit — <= 120 tablets (100 mg) or <= 120 tablets (50 mg) or <= 15 tablets (10 mg)

100 mg formulationMaximum 120 tablets per month (100 mg)

50 mg formulationMaximum 120 tablets per month (50 mg)

10 mg formulation

Provider Requirements and Authorization Process

Prior Authorization

Prior Authorization Required

Prior authorization is required for venetoclax (J8999) per Evolent processing for applicable lines of business.

Code: J8999 (venetoclax)
Prior authorization required for Commercial, Exchange/Marketplace, and Medicaid lines of business

Documentation Required

Regimen Support Limitations

Evolent does not support certain venetoclax combination regimens for Acute Lymphoblastic Leukemia (ALL) or Mantle Cell Lymphoma due to lack of Level 1 evidence (randomized clinical trials and/or meta-analyses). Authorization requests for these combinations should include rationale, alternative regimens considered, and supporting evidence when applicable.

ALL: venetoclax + chemotherapy (e.g., decitabine, hyper-CVAD, nelarabine, mini-hyper-CVD) — not supported
Mantle Cell Lymphoma: venetoclax +/- rituximab and venetoclax + ibrutinib — not supported

Definitions and Therapy Terms

inv-16: Remission induction therapy — Therapeutic regimen used to induce remission in AML, may include venetoclax combined with decitabine, azacitidine, or low-dose cytarabine

DefinitionTherapeutic regimen used to induce remission in acute myeloid leukemia (AML)

Typical combinationsMay include venetoclax combined with decitabine (Dacogen), azacitidine (Vidaza), or low‑dose cytarabine

IndicationsUsed for patients with unfavorable‑risk cytogenetics or those unsuitable for intensive induction therapy, and may be used for post‑remission or relapsed/refractory AML

Line of Therapy Specifications

first-line

First‑line AML: Venetoclax combinations (with decitabine, azacitidine, or low‑dose cytarabine) may be used as first‑line therapy for patients with AML who are unsuitable for intensive induction or who decline intensive therapy; these combinations support remission induction and post‑remission therapy.

Covers first‑line use only for patients unsuitable for intensive induction or with unfavorable‑risk cytogenetics.

first-line

First‑line CLL/SLL: Venetoclax in combination with obinutuzumab (Gazyva) may be used as first‑line therapy for CLL/SLL (coverage for first‑line specified only in combination with obinutuzumab).

First‑line monotherapy is not listed — first‑line coverage applies when given with Gazyva.

Background

Venetoclax is an oral BCL‑2 inhibitor used across multiple hematologic malignancies. In acute myeloid leukemia (AML), venetoclax is commonly administered in combination with a hypomethylating agent (decitabine or azacitidine) or with low‑dose cytarabine for patients who are unsuitable for intensive induction therapy or who have unfavorable‑risk cytogenetics; these combinations are also used for relapsed/refractory AML. For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), venetoclax is used in combination with obinutuzumab (Gazyva) for first‑ or subsequent‑line therapy, and as single‑agent therapy (with or without anti‑CD20 antibodies such as obinutuzumab or rituximab) in later lines.

Clinical use must respect safety and utilization limits: venetoclax dosing should not exceed a single dose of 400 mg, and monthly tablet limits are set at 120 tablets (100 mg), 120 tablets (50 mg), or 15 tablets (10 mg). Duration limits apply when used with anti‑CD20 agents: with obinutuzumab, venetoclax is limited to a maximum of 12 months (venetoclax component); with rituximab, use is limited to 2 years.

Evolent requires that authorization requests be supported by appropriate sources (FDA labeling, CMS‑recognized compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature). Uses lacking sufficient evidence — including unsupported combination regimens for relapsed/refractory ALL or certain mantle cell lymphoma regimens — are not supported by policy.

Revision History

2025-03policy_replacement_and_template_conversionLatest

Converted to new Evolent guideline template and replaces prior UM ONC_1297 Venclexta (venetoclax) policy.

2024-03references_and_verbiage_update

Updated references and changed NCH verbiage to Evolent.

OpenPayer

Venclexta (venetoclax) — Coverage Criteria