ZYDELIG, Idelalisib Form

Idelalisib (Zydelig®) is a kinase inhibitor. FDA Approved Indication(s) Zydelig is indicated for the treatment of relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities Limitation(s) of use:
• Zydelig is not indicated and is not recommended for first-line treatment of any patient, including patients with CLL, small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and other indolent non-Hodgkin lymphomas.
• Zydelig is not indicated and is not recommended in combination with bendamustine and rituximab, or in combination with rituximab for the treatment of patients with FL, SLL, and other indolent non-Hodgkin lymphomas.
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Zydelig is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Lymphocytic Leukemia (must meet all):

1. Diagnosis of CLL;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Relapsed/refractory disease after at least one prior therapy (see Appendix B for examples);Prior authorization may be required.
2. Prescribed as a single agent or in combination with rituximab;
   6. For Zydelig requests, member must use idelalisib, if available, unless contraindicated or clinically significant adverse effects are experienced;

3. Request meets one of the following (a or b):* a. Dose does not exceed (i and ii): i. 300 mg per day; Page 1 of 6

   CLINICAL POLICY Idelalisib ii. 2 tablets per day; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed regimen must be FDA-approved or recommended by NCCN. Approval duration:
   Medicaid/HIM – 6 months
   Commercial – 12 months or duration of request, whichever is less B. Small Lymphocytic Leukemia (off-label) (must meet all):

4. Diagnosis of SLL;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Relapsed/refractory disease after at least one prior therapy (see Appendix B for examples);Prior authorization may be required.
5. Prescribed as a single agent or in combination with rituximab;
   6. For Zydelig requests, member must use idelalisib, if available, unless contraindicated or clinically significant adverse effects are experienced;
6. Request meets one of the following (a or b): a. Dose does not exceed (i and ii): i. 300 mg per day; ii. 2 tablets per day; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN. Approval duration:
   Medicaid/HIM – 6 months
   Commercial – 12 months or duration of request, whichever is less C. Other diagnoses/indications (must meet 1 or 2):
7. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

8. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
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   CLINICAL POLICY Idelalisib II. Continued Therapy A. All Indications in Section I (must meet all):

9. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Zydelig for a covered indication and has received this medication for at least 30 days;
10. Member is responding positively to therapy;
    3. For Zydelig requests, member must use idelalisib, if available, unless contraindicated or clinically significant adverse effects are experienced;
11. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed (i and ii): i. 300 mg per day; ii. 2 tablets per day; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN. Approval duration:
    Medicaid/HIM – 12 months
    Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
12. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

13. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CLL: chronic lymphocytic leukemia FDA: Food and Drug Administration
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    CLINICAL POLICY Idelalisib FL: follicular B-cell non-Hodgkin NCCN: National Comprehensive Cancer lymphoma Network SLL: small lymphocytic lymphoma Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose Varies Varies CLL/SLL Examples of first-line, second-line and subsequent therapies: • FCR (fludarabine, cyclophosphamide, rituximab) • HDMP (high-dose methylprenisolone) + rituximab • Single-agent examples: Imbruvica® (ibrutinib); Venclexta® (venetoclax) ± Gazyva® (obinutuzumab) or rituximab; Campath® (alemtuzumab) ± rituximab; Gazyva; Copiktra® (duvelisib); Calquence® (acalabrutinib); Revlimid® (lenalidomide) ± rituximab; Arzerra® (ofatumumab) ± FC (fludarabine, cyclophosphamide); Leukeran® (chlorambucil) + rituximab Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): history of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis • Boxed warning(s): fatal and serious toxicities - hepatic, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation V. Dosage and Administration
    Indication CLL Dosing Regimen 150 mg PO BID VI. Product Availability
    Tablets: 100 mg, 150 mg Maximum Dose 300 mg per day VII.