CurrentCignaPolicy N/A

Oncology - Zydelig Prior Authorization Policy

Defines prior authorization requirements and coverage criteria for Zydelig (idelalisib tablets) for Cigna-administered health benefit plans, primarily addressing use in relapsed CLL and SLL in adults. Affects providers requesting prescription benefit coverage for Zydelig.

Policy Summary

PayerCigna

PolicyOncology - Zydelig Prior Authorization Policy

Policy CodePolicy N/A

Change TypeCriteria revised (prior therapy requirement reduced)wording clarifiedremoval of MZL criteria

Effective DateJun 4, 2025

Next Review DateJun 4, 2025

Key ActionObtain prior authorization and document prior treatment with at least one BTKi and one BCL2i; approvals are for 1 year when criteria are met.

SourceLink

POLICY UPDATE CHANGES

The requirement that the patient has tried at least two systemic regimens was changed to one systemic regimen for CLL and SLL.

Language changed from 'Venclexta-based regimen' to 'B-cell lymphoma 2 inhibitor' with example added.

Marginal Zone Lymphoma condition of approval and criteria were removed from the policy.

2Covered clinical indications

1 yrInitial approval duration

≥18Minimum patient age

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Coverage Criteria for Zydelig (idelalisib)

Chronic Lymphocytic Leukemia (FDA-approved)

Covered when ALL of the following are met for the FDA-approved CLL indication:

CLL FDA-approved indication: A) Patient is ≥ 18 years of age; AND B) Patient has tried at least one Bruton tyrosine kinase inhibitor (examples: ibrutinib, zanubrutinib, acalabrutinib, pirtobrutinib); AND C) Patient has tried at least one B-cell lymphoma 2 inhibitor (example: venetoclax).

Approve for 1 year when all conditions met

Small Lymphocytic Lymphoma (supportive evidence)

Covered when ALL of the following are met for Small Lymphocytic Lymphoma (supportive evidence use):

SLL supportive indication: A) Patient is ≥ 18 years of age; AND B) Patient has tried at least one Bruton tyrosine kinase inhibitor (examples: ibrutinib, zanubrutinib, acalabrutinib, pirtobrutinib); AND C) Patient has tried at least one B-cell lymphoma 2 inhibitor (example: venetoclax).

Approve for 1 year when all conditions met

Zydelig (idelalisib) is not indicated or recommended for first-line treatment of any patients, including those with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and other indolent non-Hodgkin lymphomas. The agent is also not indicated and not recommended in combination with bendamustine plus rituximab, or in combination with rituximab for FL, SLL, and other indolent NHLs.

Uses of Zydelig that are not explicitly covered by the criteria in this policy are considered not medically necessary and will be denied. The policy criteria will be updated as new published data become available; providers should follow the documented criteria when requesting coverage and submit supporting clinical information per the plan's requirements.

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior authorization required — approvals for 1 year

Prior authorization is recommended for prescription benefit coverage of Zydelig; if approved, authorizations are provided for 1 year when the applicable coverage criteria for CLL or SLL are met.

Step Therapy

Prior therapy required — BTKi and BCL2i

Approval requires documented prior treatment with at least one Bruton tyrosine kinase inhibitor and at least one B-cell lymphoma 2 inhibitor before initiating Zydelig.

BTKi examples listed: Imbruvica (ibrutinib), Brukinsa (zanubrutinib), Calquence (acalabrutinib), Jaypirca (pirtobrutinib).
BCL2i example listed: Venclexta (venetoclax).

Definitions and Drug/Class Examples

inv-10: Zydelig (idelalisib) — key/value summary

DrugZydelig (idelalisib)

Mechanism of actionPhosphatidylinositol 3-kinase (PI3K) inhibitor

FDA-approved indicationRelapsed chronic lymphocytic leukemia (CLL) in combination with rituximab for patients for whom rituximab alone would be considered appropriate due to comorbidities

Limitations of useNot indicated or recommended for first-line treatment of CLL, SLL, FL, and other indolent non-Hodgkin lymphomas; not recommended in combination with bendamustine plus rituximab or with rituximab for FL/SLL and other indolent NHLs.

inv-11: Bruton tyrosine kinase inhibitor (BTKi) — examples

ClassBruton tyrosine kinase inhibitor (BTKi)

Line of Therapy / Salvage Use

salvage

Relapsed/refractory setting: Use in relapsed or refractory disease after prior Bruton tyrosine kinase inhibitor and B-cell lymphoma 2 inhibitor-containing regimens; not for first-line use.

NCCN lists Zydelig as 'other recommended regimens' in this context

Covered and Not Covered Regimens / Combinations

Regimen	Indication / Notes	Coverage
Idelalisib plus rituximab
Chronic lymphocytic leukemia (relapsed CLL) in combination with rituximab for patients for whom rituximab alone would be considered appropriate therapy due to comorbidities
Covered when FDA-approved CLL criteria are met (see coverage criteria); approve for 1 year

Regimen	Indication / Notes	Coverage
Idelalisib as first-line therapy
First-line treatment of CLL, SLL, FL, and other indolent non-Hodgkin lymphomas — Zydelig is not indicated or recommended for first-line use
Not covered

Background

Zydelig (idelalisib) is a phosphatidylinositol 3-kinase (PI3K) inhibitor with an FDA indication for relapsed chronic lymphocytic leukemia in combination with rituximab for patients in whom rituximab alone would be appropriate because of comorbidities. Clinical guidance (NCCN) lists Zydelig as an other recommended regimen in relapsed/refractory CLL/SLL after prior Bruton tyrosine kinase inhibitor and B‑cell lymphoma 2 inhibitor–containing regimens. Important limitations include that Zydelig is not indicated for first-line therapy and is not recommended in certain combinations for indolent NHLs.