GLEEVEC, Imatinib Mesylate Form

Imatinib mesylate (Gleevec®) is a kinase inhibitor. FDA Approved Indication(s) Gleevec is indicated for the treatment of: • Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase • Patients with Ph+ CML in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy • Adult patients with relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) • Pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy • Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene rearrangements • Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown • Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or fluorescence in situ hybridization [FISH] demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown • Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) • Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST) • Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST 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 Gleevec is medically necessary when the following criteria are met:
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CLINICAL POLICY Imatinib I. Initial Approval Criteria
A. FDA Labeled Indications (must meet all):

1. Diagnosis of one of the following: a. Ph+ (BCR-ABL1-positive) CML or Ph+ (BCR-ABL-positive) ALL; b. MDS/MPD and member meets one of the following (i or ii): i. Disease is positive for a PDGFR mutation; ii. If the member has a diagnosis of chronic myelomonocytic leukemia (an MDS/MPD subtype), disease is positive for either a t(5;12) translocation associated with the ETV6-PDGFRβ fusion gene or PDGFRβ gene rearrangements at 5q32 (off-label); c. ASM and member meets one of the following (i-iv): i. Disease is negative for the D816V c-KIT mutation; ii. c-Kit mutational status is unknown; iii. Well-differentiated systemic mastocytosis (off-label);
   iv. Eosinophilia is present with FIP1L1-PDGFRA fusion gene (off-label); d. HES/CEL, DFSP, or GIST (a soft tissue sarcoma);
   2. Prescribed by or in consultation with an oncologist or hematologist;
2. For brand Gleevec, member must use generic imatinib, unless contraindicated or clinically significant adverse effects are experienced;
   4. Age ≥ 18 years if the diagnosis is MDS/MPD, ASM, HES/CEL, DFSP, or GIST;

3. Request meets one of the following (a or b): a. Dose does not exceed any of the following (i, ii, or iii): i. CML, DFSP, GIST: 800 mg per day; ii. ALL: 600 mg per day; iii. MDS/MPD, ASM, HES/CEL: 400 mg 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. Off-Label Indications (must meet all):

   1. Diagnosis of one of the following (a-g): a. Kaposi sarcoma (KS), and both of the following (i and ii): i. If request is for AIDS-related KS, imatinib is prescribed in combination with antiretroviral therapy; ii. Failure of liposomal doxorubicin and paclitaxel, unless clinically significant adverse effects are experienced or both are contraindicated; b. Recurrent conventional or chondroid chordoma (a bone cancer); c. KIT-positive metastatic or unresectable melanoma as second-line or subsequent therapy (i.e., following BRAF-targeted therapy); d. Desmoid tumor (also known as aggressive fibromatosis, a soft tissue sarcoma); e. Myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase fusion genes; f. Pigmented villonodular synovitis/tenosynovial giant cell tumor (a soft tissue sarcoma) as single-agent therapy; Page 2 of 9

   CLINICAL POLICY Imatinib g. Chronic graft-versus-host disease - as additional therapy in conjunction with systemic corticosteroids following no response (steroid-refractory disease) to first-line therapy options;

   2. Prescribed by or in consultation with one of the following specialists (a or b): a. AIDS-related KS: an oncologist or immunologist; b. All other diagnoses: an oncologist;
   3. Age ≥ 18 years;
4. For brand Gleevec requests, member must use generic imatinib, unless contraindicated or clinically significant adverse effects are experienced;
   5. 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).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):
   6. 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
   7. 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.
      II. Continued Therapy
      A. All Indications in Section I (must meet all):
   8. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Gleevec for a covered indication and has received this medication for at least 30 days;
   9. Member is responding positively to therapy;
5. For brand Gleevec requests, member must use generic imatinib, unless contraindicated or clinically significant adverse effects are experienced;

6. If request is for a dose increase, request meets one of the following (a or b):* a. New dose does not exceed any of the following (i, ii, or iii): i. CML, DFSP, GIST: 800 mg per day; Page 3 of 9

   CLINICAL POLICY Imatinib ii. ALL: 600 mg per day; iii. MDS/MPD, ASM, HES/CEL: 400 mg 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 - 12 months Commercial - 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

   1. 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
   2. 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 ALL: acute lymphoblastic leukemia AP: accerlated phase
      ASM: aggressive systemic mastocytosis
      BC: blast crisis CEL: chronic eosinophilic leukemia
      CML: chronic myeloid leukemia CP: chronic phase DFSP: dermatofibrosarcoma protuberans
      FDA: Food and Drug Administration
      FISH: fluorescence in situ hypridization GIST: gastrointestinal stromal tumor
      HES: hypereosinophilic syndrome KS: Kaposi sarcoma MDS: myelodysplastic syndromes
      MPD: myeloproliferative diseases
      PDGFR: platelet-derived growth factor receptor Ph+: Philadelphia chromosome positive
      PVNS/TGCT: pigmented villonodular synovitis/tenosynovial giant cell tumor Page 4 of 9

   CLINICAL POLICY Imatinib 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 See regimen See regimen liposomal doxorubicin (Doxil®, Lipodox® 50) paclitaxel AIDS-related KS 20 mg/m2 IV every 2-3 weeks with a cumulative lifetime dose of 400-450 mg/m2 due to cardiotoxicity AIDS-related KS 135 mg/m2 IV every 3 weeks or 100 mg/m2 every 2 weeks 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 None reported V. Dosage and Administration
   Indication Dosing Regimen CML Adult: • 400-600 mg/day PO for chronic phase • 600-800 mg/day PO for accelerated phase or blast crisis (800 mg given as 400 BID) ALL Pediatric: • 340 mg/m2/day PO for chronic phase
   Adult: • 600 mg/day PO for relapsed / refractory Ph+ ALL
   Pediatric: • 340 mg/m2/day PO in combination with chemotherapy for newly diagnosed Ph+ ALL Maximum Dose Adult: 800 mg/day Pediatric: 600 mg/day Adult: 600 mg/day Pediatric: 600 mg/day MDS/MPD Adult: 400 mg/day PO ASM HES/CEL DESP GIST Adult: 100-400 mg/day PO Adult: 100-400 mg/day PO Adult: 800 mg/day PO Adult: 400-800 mg/day PO for metastatic or unresectable GIST (800 mg given as 400 BID) and 400 mg/day PO or adjuvant GIST Adult: 400 mg/day Adult: 400 mg/day Adult: 400 mg/day Adult: 800 mg/day Adult: 800 mg/day; 400 mg/day for adjuvant GIST *Co-administration with strong CYP3A4 inducers may require an increased dose beyond that listed in the table. Examples of strong CYP3A4 inducers include dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital. VI. Product Availability
   Tablets: 100 mg, 400 mg Page 5 of 9

   CLINICAL POLICY Imatinib VII.