CurrentmhnPolicy CP.PHAR.129

VENCLEXTA (PDF)

Clinical policy defining medical necessity criteria, prior authorization requirements, dosing limits, covered indications (FDA-approved and selected NCCN-recommended off-label uses), continuation criteria, exclusions, and approval durations for venetoclax (Venclexta) across Commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyVENCLEXTA (PDF)

Policy CodePolicy CP.PHAR.129

Change TypeRevised; RT4 update

Effective DateJul 17, 2018

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results, other clinical information) supporting that member meets all approval criteria; prior authorization may be required for listed indications and combinations.

SourceLink

POLICY UPDATE CHANGES

4Q 2025 annual review: revised Medicaid and HIM initial approval durations to 12 months for all indications; multiple criteria updates to align with NCCN and FDA changes including CLL/SLL, AML, MM, and additional NCCN recommended uses.

RT4 (03.18.26): updated conditions under which Venclexta can be used as first-line therapy for CLL/SLL to align with FDA addition of AMPLIFY trial results to Venclexta PI.

4Q 2024 annual review: for CLL/SLL, added Gazyva as combination therapy option for relapsed/refractory disease per NCCN.

4Q 2023 annual review: for CLL/SLL indication, added option of treatment for relapse in combination with Gazyva if previously used as first-line treatment per NCCN.

2FDA-approved indications

Coverage Summary

Coverage stance: covered_with_criteria. Scope: Clinical policy defining medical necessity criteria, prior authorization requirements, dosing limits, covered indications (FDA-approved and selected NCCN-recommended off-label uses), continuation criteria, exclusions, and approval durations across Commercial, HIM, and Medicaid lines of business. FDA-approved indications: 2. NCCN-supported off-label/other covered indications (listed): 8. Standard approval duration: 12 months. Policy purpose (brief): Provide medical necessity guidance to assist coverage decisions and administer benefits for venetoclax (Venclexta).

Key thresholds & quick facts

Age requirementsGenerally ≥ 18 years for most indications; AML pathway available for newly diagnosed adults ≥ 75 years or those not candidates/declining intensive induction

Maximum dose (CLL/SLL, azacitidine/decitabine combos)400 mg per day (4 tablets/day)

Maximum dose (AML with low‑dose cytarabine)600 mg per day (6 tablets/day)

Continuation minimum exposureMember must have received medication for at least 30 days prior to renewal

Serum albumin example for BPDCN palliativeSerum albumin < 3.2 g/dL (example of low performance/nutritional status)

Initial Therapy Criteria

Initial Approval Criteria - CLL/SLL

Covered when ALL of the following are met:

ALL of the following

Base requirements
- Diagnosis of CLL or SLL
- Prescriber: Prescribed by or in consultation with an oncologist or hematologist
- Age ≥ 18 years
- Brand-to-generic: For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced

Continuation (Renewal) Criteria

Unproven / Exclusions

Applicable Codes

Product NDC / PackagingNDC

10 mg tablet	Venclexta tablet strength available (product availability listed)
50 mg tablet	Venclexta tablet strength available
100 mg tablet	Venclexta tablet strength available

Provider Actions & Billing Rules

Prior Authorization

Prior authorization required

Provider must submit documentation (office chart notes, lab results, other clinical information) supporting that member meets all approval criteria; prior authorization may be required for listed indications and combinations.

Documentation Required

Clinical documentation required

Prescriber must submit supporting evidence when dose or off-label use is supported by practice guidelines or peer‑reviewed literature; for prior therapy requirements see Appendix B.

Clinical Evidence & References

Evidence/citation list: 1) Venclexta Prescribing Information. AbbVie; February 2026. 2) National Comprehensive Cancer Network Drugs & Biologics Compendium and disease-specific NCCN guidelines (CLL, AML, MM, Waldenström, amyloidosis, etc.). Note: the policy references the Venclexta Prescribing Information (Feb 2026) and the NCCN Drugs & Biologics Compendium and disease-specific NCCN guidelines. (The policy’s internal stats bar counts are not duplicated here.)

Evidence / Guideline quick reference

Prescribing Information (most recent PI)Venclexta Prescribing Information. AbbVie; February 2026

Guideline sourceNCCN Drugs & Biologics Compendium and disease-specific NCCN guidelines (e.g., CLL, AML, MM, Waldenström, amyloidosis)

Background

Venetoclax (Venclexta) is a BCL-2 (B-cell lymphoma 2) inhibitor. It has FDA approvals for CLL/SLL and for newly-diagnosed AML in combination with azacitidine, decitabine, or low‑dose cytarabine for adults meeting specified criteria. The policy incorporates selected NCCN‑recommended off‑label uses with specific criteria and dosing limits and aligns coverage and dosing (including maximum doses and ramp‑up schedules) with the FDA prescribing information and NCCN guidance.

Definitions / quick term reference

BPDCNBlastic plasmacytoid dendritic cell neoplasm

CLLChronic lymphocytic leukemia

SLLSmall lymphocytic lymphoma

NCCNNational Comprehensive Cancer Network

IPSS-RRevised International Prognostic Scoring System

Revision History

4Q 2025revisedLatest

4Q 2025 annual review: revised Medicaid and HIM initial approval durations to 12 months for all indications; removed certain relapse/previous-use requirements for CLL/SLL combinations per NCCN; added FDA-labeled AML option for age ≥ 75 years and replaced 'newly diagnosed' with 'induction, post-induction, or consolidation therapy'; simplified relapsed/refractory criteria; added CNS option for MM; added adult ALL supported uses and MDS to additional NCCN recommended uses; added CMML-2, hairy cell leukemia, myeloproliferative neoplasm, and pediatric ALL off-label uses; references reviewed and updated.

4Q 2024revised

4Q 2024 annual review: for CLL/SLL, added Gazyva as combination therapy option for relapsed/refractory disease per NCCN.

ref_orig_caretaker_error_fixing_removed_duplicate_fields_placeholder_1_fixing_invalid_json_keys_removed unknown_field_cleanup_1": "b1_0"} }, { "ref": "b1_1", "citations": [ "5", "6", "23", "24" ], "title": "Initial Approval Criteria - Myeloid Leukemias", "intro": "Covered when ALL of the following are met:", "nodes": [ "{\"operator\":\"all\",\"n\":0,\"label\":\"\",\"text\":\"\",\"threshold\":\"\",\"note\":\"\",\"children\":[{\"operator\":\"all\",\"n\":0,\"label\":\"Base requirements\",\"text\":\"\",\"threshold\":\"\",\"note\":\"\",\"children\":[{\"operator\":\"all\",\"n\":0,\"label\":\"Diagnosis\",\"text\":\"Diagnosis of AML or blastic plasmacytoid dendritic cell neoplasm (BPDCN)\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Prescriber\",\"text\":\"Prescribed by or in consultation with an oncologist or hematologist\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Age\",\"text\":\"Age ≥ 18 years\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Brand-to-generic\",\"text\":\"For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced\",\"threshold\":\"\",\"note\":\"\",\"children\":[]}]},{\"operator\":\"any\",\"n\":0,\"label\":\"If diagnosis is AML, one of the following\",\"text\":\"\",\"threshold\":\"\",\"note\":\"\",\"children\":[{\"operator\":\"all\",\"n\":0,\"label\":\"Induction/post-induction/consolidation pathway\",\"text\":\"Venclexta prescribed for induction, post-induction, or consolidation therapy and one of: Age ≥ 75 years and disease is newly diagnosed; or member is not a candidate for or declines use of intensive induction chemotherapy\",\"threshold\":\"\",\"note\":\"(see Appendix B for examples)\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Relapsed/refractory disease\",\"text\":\"Disease is relapsed/refractory\",\"threshold\":\"\",\"note\":\"(see Appendix B for examples)\",\"children\":[]} ]},{\"operator\":\"all\",\"n\":0,\"label\":\"Combination requirement\",\"text\":\"Prescribed in combination with azacitidine, decitabine, or low-dose (20 mg/m2) cytarabine\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"any\",\"n\":0,\"label\":\"Dose limits for AML combinations\",\"text\":\"\",\"threshold\":\"\",\"note\":\"\",\"children\":[{\"operator\":\"all\",\"n\":0,\"label\":\"Azacitidine/decitabine combo\",\"text\":\"Dose does not exceed 400 mg per day and does not exceed 4 tablets per day\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Low-dose cytarabine combo\",\"text\":\"Dose does not exceed 600 mg per day and does not exceed 6 tablets per day\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Guideline-supported dose\",\"text\":\"Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)\",\"threshold\":\"\",\"note\":\"\",\"children\":[]} ]},{\"operator\":\"all\",\"n\":0,\"label\":\"Regimen source\",\"text\":\"Prescribed regimen must be FDA-approved or recommended by NCCN\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"If diagnosis is BPDCN\",\"text\":\"If diagnosis is BPDCN, one of: disease is systemic and request is for palliative treatment (e.g., low performance/nutritional status such as serum albumin < 3.2 g/dL; not a candidate for intensive remission therapy or tagraxofusp-erzs) OR disease is relapsed/refractory\",\"threshold\":\"\",\"note\":\"\",\"children\":[]}]}]" ] }, { "ref": "b1_2", "citations": [ "7" ], "title": "Initial Approval Criteria - Mantle Cell Lymphoma (off-label)", "intro": "Covered when ALL of the following are met:", "nodes": [ "{\"operator\":\"all\",\"n\":0,\"label\":\",\"text\":\"\",\"threshold\":\"\",\"note\":\"\",\"children\":[{\"operator\":\"all\",\"n\":0,\"label\":\"Base requirements\",\"text\":\"\",\"threshold\":\"\",\"note\":\"\",\"children\":[{\"operator\":\"all\",\"n\":0,\"label\":\"Diagnosis\",\"text\":\"Diagnosis of mantle cell lymphoma\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Prescriber\",\"text\":\"Prescribed by or in consultation with an oncologist or hematologist\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Age\",\"text\":\"Age ≥ 18 years\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Brand-to-generic\",\"text\":\"For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced\",\"threshold\":\"\",\"note\":\"\",\"children\":[]}]},{\"operator\":\"any\",\"n\":0,\"label\":\"Permitted regimens\",\"text\":\"Venclexta is prescribed as one of the following regimens: single agent as subsequent therapy; in combination with rituximab or Imbruvica as subsequent therapy; OR in combination with Gazyva and Imbruvica when both: disease is positive for TP53 mutation AND a clinical trial is not available (a clinical trial is strongly recommended)\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Dose requirement\",\"text\":\"Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Regimen source\",\"text\":\"Prescribed regimen must be FDA-approved or recommended by NCCN\",\"threshold\":\"\",\"note\":\"\",\"children\":[]}]}" ] }, { "ref": "b1_3", "citations": [ "8" ], "title": "Initial Approval Criteria - Multiple Myeloma (off-label)", "intro": "Covered when ALL of the following are met:", "nodes": [ "{\"operator\":\"all\",\"n\":0,\"label\":\"\",\"text\":\"\",\"threshold\":\"\",\"note\":\"\",\"children\":[{\"operator\":\"all\",\"n\":0,\"label\":\"Diagnosis\",\"text\":\"Diagnosis of multiple myeloma with t(11;14) translocation\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Prescriber\",\"text\":\"Prescribed by or in consultation with an oncologist or hematologist\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Age\",\"text\":\"Age ≥ 18 years\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Brand-to-generic\",\"text\":\"For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"any\",\"n\":0,\"label\":\"Permitted uses\",\"text\":\"Member has central nervous system (CNS) disease with no other options available OR member has received ≥ 1 prior therapy and Venclexta is prescribed in combination with dexamethasone\",\"threshold\":\"\",\"note\":\"(see Appendix B for examples)\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Dose requirement\",\"text\":\"Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Regimen source\",\"text\":\"Prescribed regimen must be FDA-approved or recommended by NCCN\",\"threshold\":\"\",\"note\":\"\",\"children\":[]}]}" ] }, { "ref": "b1_4", "citations": [ "9", "10" ], "title": "Initial Approval Criteria - Additional NCCN Recommended Uses (off-label)", "intro": "Covered when ALL of the following are met:", "nodes": [ "{\"operator\":\"all\",\"n\":0,\"label\":\"\",\"text\":\"\",\"threshold\":\"\",\"note\":\"\",\"children\":[{\"operator\":\"any\",\"n\":0,\"label\":\"Supported diagnoses\",\"text\":\"Member has one of the following diagnoses:\",\"threshold\":\"\",\"note\":\"\",\"children\":[{\"operator\":\"all\",\"n\":0,\"label\":\"CMML-2\",\"text\":\"CMML-2, with Venclexta prescribed in combination with a hypomethylating agent (e.g., azacitidine or decitabine)\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Higher-risk MDS\",\"text\":\"Myelodysplastic syndrome (MDS) that is higher-risk (IPSS-R intermediate, high, or very high), with Venclexta prescribed in combination with either azacitadine or decitabine\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Hairy cell leukemia\",\"text\":\"Hairy cell leukemia that is relapsed/refractory\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Myeloproliferative neoplasm\",\"text\":\"Myeloproliferative neoplasm, with Venclexta prescribed in combination with hypomethylating agents\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"any\",\"n\":0,\"label\":\"ALL supported uses\",\"text\":\"Acute lymphoblastic leukemia (ALL) supported uses: pediatric relapsed/refractory ALL; T-cell ALL relapsed/refractory; or Philadelphia chromosome negative B-cell ALL in adults meeting age/comorbidity criteria (age ≥ 18 with substantial comorbidities OR age ≥ 65)\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Amyloidosis\",\"text\":\"Systemic light chain amyloidosis that is relapsed/refractory\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Waldenström\",\"text\":\"Waldenström macroglobulinemia/lymphoplasmacytic lymphoma, with Venclexta prescribed as a single agent\",\"threshold\":\"\",\"note\":\"\",\"children\":[]} ]},{\"operator\":\"all\",\"n\":0,\"label\":\"Prescriber\",\"text\":\"Prescribed by or in consultation with an oncologist or hematologist\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Age requirement\",\"text\":\"For all indications except pediatric ALL: Age ≥ 18 years\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Brand-to-generic\",\"text\":\"For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Prior therapy requirement\",\"text\":\"For hairy cell leukemia, pediatric ALL, systemic light chain amyloidosis, and Waldenström macroglobulinemia/lymphoplasmacytic lymphoma: Member has received ≥ 1 prior therapy\",\"threshold\":\"\",\"note\":\"(see Appendix B for examples)\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Dose requirement\",\"text\":\"Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Regimen source\",\"text\":\"Prescribed regimen must be FDA-approved or recommended by NCCN\",\"threshold\":\"\",\"note\":\"\",\"children\":[]}]}" ] }, { "ref": "b1_5", "citations": [ "11", "14" ], "title": "Other diagnoses/indications", "intro": "", "nodes": [ "{\"operator\":\"any\",\"n\":0,\"label\":\"Options for other uses\",\"text\":\"If drug label changed within last 6 months not reflected in policy, refer to formulary/no coverage or non-formulary policies listed (CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16) OR if requested use is not listed in section III and criterion above does not apply, refer to off-label use policy CP.CPA.09, HIM.PA.154, CP.PMN.53\",\"threshold\":\"\",\"note\":\"\",\"children\":[]} ]" }, { "ref": "b2_0", "citations": [ "12" ], "title": "Continuation (Renewal) Criteria - All Indications in Section I", "intro": "Covered when ALL of the following are met:", "nodes": [ "{\"operator\":\"all\",\"n\":0,\"label\":\"\",\"text\":\"\",\"threshold\":\"\",\"note\":\"\",\"children\":[{\"operator\":\"all\",\"n\":0,\"label\":\"Current therapy\",\"text\":\"Currently receiving medication 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\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Response\",\"text\":\"Member is responding positively to therapy\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Brand-to-generic\",\"text\":\"For brand Venclexta requests, member must use generic venetoclax, if available, unless contraindicated or clinically significant adverse effects are experienced\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"AML combination requirement\",\"text\":\"For AML, prescribed in combination with azacitidine, decitabine, or low-dose (20 mg/m2) cytarabine\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"any\",\"n\":0,\"label\":\"If request is for a dose increase, one of the following\",\"text\":\"\",\"threshold\":\"\",\"note\":\"\",\"children\":[{\"operator\":\"all\",\"n\":0,\"label\":\"CLL/SLL or azacitidine/decitabine for AML\",\"text\":\"New dose does not exceed 400 mg per day and does not exceed 4 tablets per day\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Low-dose cytarabine for AML\",\"text\":\"New dose does not exceed 600 mg per day and does not exceed 6 tablets per day\",\"threshold\":\"\",\"note\":\"\",\"children\":[]},{\"operator\":\"all\",\"n\":0,\"label\":\"Guideline-supported increase\",\"text\":\"New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)\",\"threshold\":\"\",\"note\":\"\",\"children\":[]} ]}] }" ] }, { "ref": "b3_0", "citations": [ "14" ], "title": "Diagnoses/Indications Not Authorized", "intro": "", "nodes": [ "{\"operator\":\"all\",\"n\":0,\"label\":\"Exclusion summary\",\"text\":\"Non-FDA approved indications which are not addressed in this policy are not authorized unless there is sufficient documentation of efficacy and safety according to off-label use policies CP.CPA.09, HIM.PA.154, CP.PMN.53 or evidence of coverage documents\",\"threshold\":\"\",\"note\":\"\",\"children\":[]} ] } ]}