CurrentHealth NetPolicy CP PHAR.129

Venetoclax (Venclexta) — Coverage Criteria

Defines medical necessity, authorization criteria, and coverage conditions for venetoclax (Venclexta) across multiple hematologic malignancy indications for Health Net lines of business (Commercial, HIM, Medicaid). Applies to providers requesting coverage for members.

Policy Summary

PayerHealth Net

PolicyVenetoclax (Venclexta) — Coverage Criteria

Policy CodePolicy CP PHAR.129

Change TypeNo material changes

Effective Date07.17.18

Next Review DateN/A

Key ActionProvider must submit documentation (office notes, labs, or other clinical information) showing the member meets all approval criteria and prior authorization may be required.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3Lines of business

Age ≥18Adult indications

6–12 moApproval durations

400 mg/dayCLL/SLL max dose

Coverage Criteria for Venetoclax (Venclexta)

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CLL/SLL initial criteria: 1. Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age ≥ 18 years; 4. For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced; 5. Request meets one of the following: a) Prescribed as first-line therapy or for relapse if previously used as first-line therapy in combination with obinutuzumab (Gazyva); or b) Prescribed as subsequent therapy for relapsed/refractory disease as a single agent or in combination with rituximab or obinutuzumab; 6. Dose does not exceed 400 mg/day and 4 tablets/day unless supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).dose <= 400 mg/day unless supported

Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Therapy — AML/BPDCN

Covered when ALL of the following are met

Myeloid leukemias initial criteria: 1. Diagnosis of acute myeloid leukemia (AML) or blastic plasmacytoid dendritic cell neoplasm (BPDCN); 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age ≥ 18 years; 4. For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced; 5. If AML: disease is newly diagnosed and member is not a candidate for or declines intensive induction chemotherapy, or disease is relapsed/refractory after induction therapy; if BPDCN: disease is systemic or relapsed/refractory as specified; 6. Prescribed in combination with azacitidine, decitabine, or low‑dose (20 mg/m2) cytarabine as applicable; dosing limits: 400 mg/day (4 tablets/day) when combined with azacitidine or decitabine; 600 mg/day (6 tablets/day) when combined with low‑dose cytarabine; 7. Dose exceeding limits must be supported by practice guidelines or peer‑reviewed literature (prescriber must submit evidence).400 mg/day azacitidine/decitabine; 600 mg/day with low-dose cytarabine

Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Therapy — Mantle Cell Lymphoma (off-label)

Covered when ALL of the following are met

Mantle cell lymphoma criteria: 1. Diagnosis of mantle cell lymphoma; 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age ≥ 18 years; 4. For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced; 5. Venclexta is prescribed as one of the following regimens: a) single agent as subsequent therapy; b) in combination with rituximab or ibrutinib as subsequent therapy; or c) in combination with obinutuzumab (Gazyva) and ibrutinib when TP53 mutation positive and a clinical trial is not available (clinical trial strongly recommended); 6. Dose is within FDA maximum limit for any FDA‑approved indication or is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).dose within FDA max or supported by literature

Prescribed regimen must be FDA‑approved or recommended by NCCN; clinical trial strongly recommended when specified.

Initial Therapy — Additional NCCN Recommended Uses (off-label)

Covered when ALL of the following are met

NCCN recommended uses: 1. Diagnosis of one of the following NCCN‑recommended indications: a) chronic myelomonocytic leukemia (CMML)-2 with venetoclax in combination with hypomethylating agents; b) relapsed/refractory hairy cell leukemia; c) pediatric relapsed/refractory acute lymphoblastic leukemia (ALL); d) myeloproliferative neoplasm with venetoclax in combination with hypomethylating agents; e) systemic light chain amyloidosis relapsed/refractory; f) Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma with venetoclax as single agent; 2. Prescribed by or in consultation with an oncologist or hematologist; 3. For all indications except pediatric ALL: age ≥ 18 years (pediatric ALL per age definition); 4. Prior therapy requirements as specified for individual diagnoses (see Appendix B) where applicable; 5. For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced; 6. Dose is within FDA maximum limit for any FDA‑approved indication or is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).age and prior therapy per indication

Prescribed regimen must be FDA‑approved or recommended by NCCN; prior authorization may be required.

Continued Therapy

Covered for continuation when ALL of the following are met

Continued therapy general criteria: 1. Member is currently receiving venetoclax via Centene benefit, or documentation supports that member is currently receiving Venclexta for a covered indication and has received this medication for at least 30 days; 2. Member is responding positively to therapy; 3. For AML, therapy must be continued in combination with azacitidine, decitabine, or low‑dose (20 mg/m2) cytarabine as applicable; 4. For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced; 5. If request is for a dose increase, new dose does not exceed specified limits (400 mg/day; or 600 mg/day with low‑dose cytarabine) or the increase is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).>=30 days prior use; response to therapy required

Approval durations specified by line of business; prior authorization may be required.

Initial Therapy — Diagnosis-specific Criteria

Initial Therapy

Initial therapy coverage requires diagnosis-specific criteria and supporting documentation

Initial therapy nodes: See indication‑specific initial approval criteria sets for CLL/SLL, AML/BPDCN, mantle cell lymphoma, multiple myeloma with t(11;14), and additional NCCN‑recommended uses; for brand requests use generic venetoclax when available unless contraindicated; prescriber must be an oncologist or hematologist or be in consultation; prescribed regimen must be FDA‑approved or recommended by NCCN; prior authorization may be required.

Refer to each indication's criteria for specific dosing limits and prior therapy requirements.

Initial therapy/ramp‑up

Initial dosing/ramp‑up

CLL/SLL initial ramp‑up: CLL/SLL ramp‑up schedule: 20 mg PO QD for 1 week, then 50 mg PO QD for 1 week, then continue ramp‑up per product dosing to reach 400 mg PO QD (5‑week ramp‑up schedule); start combination timing per regimen (e.g., with obinutuzumab/Gazyva or rituximab) as specified in regimen guidance.

Avoid concomitant use with strong CYP3A inhibitors at initiation and during ramp‑up for CLL/SLL per contraindication guidance; prescriber must document dosing schedule.

AML initial therapy

AML dosing when used in combination

AML dosing: Titrate venetoclax per product escalation (e.g., to 100 mg/day, 200 mg/day, 400 mg/day) then continue: in combination with azacitidine or decitabine use 400 mg/day (4 tablets/day); in combination with low‑dose cytarabine use 600 mg/day (6 tablets/day) until disease progression or unacceptable toxicity; dose increases beyond these limits must be supported by guidelines or literature (prescriber must submit evidence).400 mg/day or 600 mg/day depending on combination

Prescribed regimen must be FDA‑approved or recommended by NCCN; prior authorization may be required.

Provider Actions, Documentation, and Prior Authorization

Prior Authorization

Prior Authorization Required

Requests for Venclexta (venetoclax) may be subject to prior authorization. Provider must submit supporting clinical documentation (office notes, labs, pathology, prior therapy records) demonstrating the member meets the applicable approval criteria in this policy.

Prior authorization may be required for certain indications and lines of therapy per the approval criteria.
Submit documentation showing prescribing clinician is an oncologist or hematologist or that the request is in consultation with one when required.

Denial Risk

Non‑covered / Off‑label Indications Risk

Non‑FDA approved (off‑label) indications are not authorized unless there is sufficient documentation of efficacy and safety per the health plan off‑label use policies (CP.CPA.09 for commercial, HIM.PA.154 for HIM, CP.PMN.53 for Medicaid) or other evidence of coverage documents. Coverage for NCCN‑recommended off‑label uses is addressed in this policy when specific criteria and supporting evidence are provided.

Diagnoses/Indications not addressed in this policy are considered not authorized unless sufficient off‑label documentation is provided.
NCCN‑recommended off‑label indications included in this policy require the prescriber to submit supporting evidence as specified.

Documentation Required

Off‑label Indications Not Authorized Without Documentation

Off‑label indications will not be authorized without prescriber documentation supporting that the requested regimen is FDA‑approved for the indication or recommended by NCCN, or that peer‑reviewed literature/practice guidelines justify the use. The prescriber must submit supporting evidence when requesting coverage for off‑label use.

Prescriber must submit citations or clinical evidence supporting off‑label dosing or regimen.
If dose or regimen exceeds FDA limits, documentation must show support by guidelines or peer‑reviewed literature.

Step Therapy

Generic‑first / Prior Therapy Expectations

Generic‑first expectation: for brand Venclexta requests, member must use generic venetoclax if available unless clinically contraindicated or the member experiences clinically significant adverse effects. Prior therapy/step requirements apply where specified in the clinical criteria (see Appendix B for examples of prior therapy and therapeutic alternatives).

Brand requests require documentation why generic venetoclax is not appropriate (contraindication or adverse effect).
Prior therapy examples and alternative therapies are listed in Appendix B and must be documented when required by the criteria.

Documentation Required

Required Documentation

Provider must submit documentation (such as office chart notes, lab results, pathology, prior therapy records) supporting that member has met all approval criteria, including indication, prior therapies, dosing rationale, and any safety considerations (e.g., CYP3A interactions, tumor lysis risk).

Documentation must demonstrate diagnosis, age, specialty consultation, prior treatment history (see Appendix B), and dosing within FDA limits or supported by guidelines.
Evidence supporting off‑label uses (NCCN recommendation or peer‑reviewed literature) must be included when applicable.

Documentation Required

Dosing and Contraindication Documentation

Dosing must be consistent with FDA‑approved regimens or supported by practice guidelines/peer‑reviewed literature for off‑label uses. Documented contraindications (for example, inability to use generic formulation) and safety considerations (such as concomitant strong CYP3A inhibitors during ramp‑up) must be provided.

Ensure dosing does not exceed FDA maximum limits for the indication unless justified by guidelines/literature.
Document any contraindications (e.g., CYP3A strong inhibitor use) and management plans per the product labeling.

Continuation and Maintenance Therapy

Continuation

Continued therapy nodes: Member must have been receiving Venclexta for at least 30 days, be responding positively to therapy, AML combinations must continue with azacitidine, decitabine, or low‑dose cytarabine as applicable; for CLL/SLL continue 400 mg PO QD after ramp‑up until disease progression or per defined course when in combination (e.g., with rituximab continue 400 mg QD for 24 months); use generic when available unless contraindicated; dose increase requests must meet dosing limits or be supported by guidelines/literature.>=30 days prior use; 400 mg/day for CLL/SLL

Approval durations vary by line of business (e.g., Commercial 12 months or duration of request).

Continuation/maintenance dosing

CLL/SLL continuation: Continue venetoclax 400 mg PO QD after completion of the 5‑week ramp‑up schedule until disease progression or per defined course when used in combination (with rituximab continue 400 mg QD for 24 months from Cycle 1 of rituximab; with obinutuzumab follow regimen‑specific guidance); for AML combinations continue at the combination‑specific maintenance dose (400 mg/day with azacitidine/decitabine; 600 mg/day with low‑dose cytarabine) until progression or unacceptable toxicity.400 mg/day (CLL/SLL); 400 mg/day or 600 mg/day (AML combinations)

Prescriber must adhere to combination‑specific duration guidance and document response.

Step Therapy and Prior Authorization Sequencing

Requirement	Policy detail
Generic-first expectation for brand requests
For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced.
Prior therapy / step expectations for off-label uses
Prior therapies may be required for certain off-label indications (see Appendix B examples); specific prior therapy examples and sequences are referenced in appendices and NCCN guidance.

Alignment topic	Policy statement / history
NCCN alignment and updates
Policy and prior annual reviews revised criteria to align with NCCN recommendations and to add NCCN‑supported off‑label indications (examples added include BPDCN, systemic light chain amyloidosis, Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma, and multiple myeloma per NCCN).
Prior review template changes
Template and reference updates were applied across diagnoses; generic oral oncology agent redirection language was added during annual reviews (dates and P&T approval noted in references).

Definitions and Abbreviations

BCL‑2 definition

TermBCL-2 (B-cell lymphoma 2) protein; pharmacologic target of venetoclax

RoleAnti-apoptotic protein overexpressed in certain hematologic malignancies

RelevanceInhibition of BCL-2 by venetoclax promotes apoptosis of malignant B-cells

NCCN definition

AcronymNCCN = National Comprehensive Cancer Network

PurposeProvides evidence-based cancer treatment guidelines and recommended regimens referenced in this policy

Policy useNCCN recommendations are accepted as support for coverage of off-label venetoclax uses when criteria are met

ALL definition

AcronymALL = acute lymphoblastic leukemia

ScopeIncludes pediatric relapsed/refractory ALL among NCCN-recommended off-label uses referenced in policy

Relevance to policyRecognized diagnosis abbreviation used in appendices and coverage criteria

AML definition

AcronymAML = acute myeloid leukemia

Policy contextAML is an FDA‑approved venetoclax indication when used in combination with azacitidine, decitabine, or low‑dose cytarabine in specific populations

Dose limitsPolicy specifies 400 mg/day with azacitidine/decitabine and 600 mg/day with low‑dose cytarabine

BPDCN definition

AcronymBPDCN = blastic plasmacytoid dendritic cell neoplasm

Policy contextListed among NCCN‑supported off‑label hematologic malignancy uses that may be covered when criteria are met

Clinical relevanceRare myeloid-lineage neoplasm referenced in appendices as a recognized diagnosis abbreviation

CLL definition

AcronymCLL = chronic lymphocytic leukemia

Policy contextPrimary FDA‑approved indication for venetoclax; coverage criteria and ramp‑up schedule specified in dosing section

Maintenance dosingMaximum/maintenance dose for CLL/SLL specified as 400 mg/day

OpenPayer

Venetoclax (Venclexta) — Coverage Criteria

Coverage Criteria for Venetoclax (Venclexta)

Initial Therapy — Diagnosis-specific Criteria

Provider Actions, Documentation, and Prior Authorization

Continuation and Maintenance Therapy

Dosing Schedules and Code-related Notes

Step Therapy and Prior Authorization Sequencing

Background on Venetoclax

Definitions and Abbreviations