Centene thioguanine Coverage Policy Update

Coverage Criteria and Clinical Requirements

Initial Therapy — AML

Covered when ALL of the following are met for Acute Myeloid Leukemia (AML):

AML initial: 1. Diagnosis of acute myeloid leukemia (AML). 2. Prescribed by or in consultation with an oncologist or hematologist. 3. Prescribed for remission induction or remission consolidation therapy. 4. Member must use thioguanine (Tabloid) if available unless contraindicated or clinically significant adverse effects are experienced. 5. Dose does not exceed 3 mg/kg per day OR the dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). 6. Prescribed regimen must be FDA‑approved or recommended by the NCCN. Approval duration: 3 months.

Refer to package insert for AML dosing; providers may be required to submit protocol dosing if different from label.

Initial Therapy — ALL (off-label)

Covered when ALL of the following are met for ALL (off‑label):

ALL initial: 1. Diagnosis of acute lymphoblastic leukemia (ALL). 2. Prescribed by or in consultation with an oncologist or hematologist. 3. Disease subtype: Philadelphia chromosome‑negative OR Philadelphia chromosome‑positive when prescribed in combination with a tyrosine kinase inhibitor. 4. Member must use thioguanine (Tabloid) if available unless contraindicated or clinically significant adverse effects are experienced. 5. Prescribed regimen must be FDA‑approved or recommended by the NCCN. 6. Dose is within the FDA maximum limit for any FDA‑approved indication OR the dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). Approval duration: 3 months.

Off‑label use — supporting evidence required.

Initial Therapy — Glioma (pilocytic astrocytoma) (off-label)

Covered when ALL of the following are met for recurrent/progressive pilocytic astrocytoma (PA) in adults (off‑label):

Glioma initial: 1. Diagnosis of recurrent or progressive pilocytic astrocytoma (PA). 2. Age > 18 years. 3. Prescribed by or in consultation with an oncologist or hematologist. 4. Prescribed in combination with PCV (procarbazine, lomustine, vincristine); carmustine may be used in place of lomustine. 5. Member must use thioguanine (Tabloid) if available unless contraindicated or clinically significant adverse effects are experienced. 6. Dose is within the FDA maximum limit for any FDA‑approved indication OR the dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). 7. Prescribed regimen must be FDA‑approved or recommended by the NCCN. Approval duration: 3 months.

Off‑label — NCCN referenced.

Continued Therapy

Covered for continuation when ALL of the following are met:

Continuation: 1. Member is currently receiving Tabloid via the Centene benefit OR documentation supports current use and at least 30 days of therapy. 2. Member is responding positively to therapy. 3. For dose increases: new dose does not exceed 3 mg/kg per day OR the new dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). 4. Member must use thioguanine (Tabloid) if available unless contraindicated or clinically significant adverse effects are experienced. Approval duration: 3 months.

Providers may be required to submit documentation (e.g., chart notes, labs) and protocol dosing if dosing differs from package insert.

Other Indications / Non‑standard Uses

Other diagnoses/indications (not specifically listed) — one of the following must be met:

Other indications: a) If the drug is on the formulary/PDL: follow the no coverage criteria policy for the relevant line of business (HIM.PA.33 for marketplace; CP.PMN.255 for Medicaid). OR b) If the drug is NOT on the formulary/PDL: follow the non‑formulary policy for the relevant line of business (HIM.PA.103 for marketplace; CP.PMN.16 for Medicaid). If the requested use (diagnosis, age, dosing) is not listed in section III and neither a) nor b) apply, refer to the off‑label use policy for the relevant line of business (HIM.PA.154 for marketplace; CP.PMN.53 for Medicaid).

Follow referenced payer policies.

Summary criteria updates

Coverage and criteria updates summarized from annual reviews

AML dosing limited to package insert information or provider‑submitted protocol dosing information.

Requirement for remission induction/consolidation moved to AML per FDA label and NCCN.

ALL off-label use: ALL criteria revised to require combination with a tyrosine kinase inhibitor where applicable (replacing explicit Sprycel/imatinib listing); age restrictions removed per NCCN Compendium.

Age and prior relapsed/refractory requirements revised across prior reviews.

Glioma (pilocytic astrocytoma) off-label use: Pilocytic astrocytoma added as an off‑label indication per NCCN; prior requirement for fractionated external beam radiation therapy was removed.

Approval durations for Legacy WellCare consolidated to 3 months.

Thioguanine (Tabloid) is FDA‑approved for remission induction and remission consolidation treatment of acute nonlymphocytic leukemia (acute myeloid leukemia, AML) and is not recommended for maintenance therapy because of the high risk of liver toxicity. It is not effective for chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, or solid tumors; therefore requests for these diagnoses are not supported by the product label and are excluded from coverage under this policy unless compelling supporting evidence is provided. Restaging or alternate uses must follow the off‑label policies referenced elsewhere in this document.

Requests for indications that are non‑FDA approved and not specifically addressed in this policy may be considered only when the prescriber provides sufficient documentation of efficacy and safety consistent with the plan’s off‑label use policies (see HIM.PA.154 for marketplace and CP.PMN.53 for Medicaid). Absent such documentation, these uses are considered not authorized.

For members enrolled in Medicaid, state Medicaid coverage provisions take precedence when they conflict with the coverage provisions in this clinical policy. Providers should consult the applicable state Medicaid manual for any differing coverage requirements that supersede this policy.

Non‑FDA approved indications that are not explicitly addressed in this policy are not authorized unless the prescriber submits sufficient documentation demonstrating efficacy and safety in accordance with the plan’s off‑label use policies (HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or applicable evidence of coverage documents. Requests lacking this supporting evidence may be denied.

This clinical policy is intended as a guide to medical necessity to assist in coverage decision-making and benefit administration. It does not constitute a guarantee of payment or a contract. Coverage determinations remain subject to the terms, conditions, exclusions, and limitations of the member’s coverage documents and applicable law and regulation; failure to meet plan requirements may result in denial of coverage.

Coding and Dose Limits

Codes referencedmixed

N/A	No explicit CPT/HCPCS/ICD-10/NDC codes listed in this document portion

Prior authorization affected codesmixed

affected codes

document refers to affected codes for prior authorization but specific codes not present in this excerpt

inv-13: Maximum daily dose

Maximum daily dose3 mg/kg per day (dose may be increased from ~2 mg/kg/day to 3 mg/kg/day if no response after ~4 weeks; total daily dose may be given at one time)

Initial typical starting dose (AML single-agent)Approximately 2 mg/kg/day

Dose increase guidanceIf no clinical improvement after 4 weeks and no leukocyte or platelet depression, dosage may be cautiously increased to 3 mg/kg/day

inv-14: approval duration (Legacy WellCare)

Standard approval duration (Legacy WellCare consolidated)3 months

Approval duration for initial and continued therapyTypically 3 months per documented criteria

Authorization, Documentation, and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for initiation and continuation of thioguanine (Tabloid). Prescribers must document that the request meets the clinical criteria in this policy. Initial approvals are granted for up to 3 months.

Prescriber: must be an oncologist or hematologist or in consultation with one for AML indications.
Initial approval: diagnosis of AML for induction or consolidation therapy; prescribed regimen must be FDA‑approved or recommended by NCCN.
For Tabloid requests, member must use thioguanine if available unless contraindicated or clinically significant adverse effects are experienced.
Dose limit: dose does not exceed 3 mg/kg per day unless supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).
Continuation: member is currently receiving medication via the Centene benefit or has received Tabloid for at least 30 days and is responding positively to therapy.

Documentation Required

Drug Background and Scope

Thioguanine (Tabloid) is an antimetabolite indicated for remission induction and remission consolidation of acute nonlymphocytic leukemia (acute myeloid leukemia, AML). The product is not recommended for maintenance therapy due to the risk of serious liver toxicity. Clinically, thioguanine is ineffective for certain hematologic malignancies and many solid tumors; see policy exclusions for specific diagnoses not supported by the label. Prescribers seeking coverage for off‑label uses must document supporting evidence per the plan’s off‑label policies.

Definitions and Off-label Use Notes

inv-24: AML — definition/key term

DefinitionAML: acute myeloid leukemia

FDA‑labeled useRemission induction and remission consolidation treatment of acute nonlymphocytic leukemia (AML)

Maintenance therapy recommendationThioguanine is not recommended for maintenance therapy due to risk of liver toxicity

inv-25: ALL — definition/key term

DefinitionALL: acute lymphoblastic leukemia

Policy statusListed as an off-label indication for thioguanine when criteria are met

Combination therapy note

Line of Therapy Designations

first-line

first-line: Prescribed for remission induction or remission consolidation treatment of AML per FDA label; not recommended for maintenance therapy due to high risk of liver toxicity.

salvage

salvage: Requirement for use as remission induction/consolidation moved from ALL to AML per FDA label and NCCN.

Biomarker / Genetic Test Requirements

inv-29: Philadelphia chromosome (BCR-ABL) — biomarker note.

BiomarkerPhiladelphia chromosome (BCR-ABL)

Clinical implicationPresence of Philadelphia chromosome in ALL guides therapy: Philadelphia chromosome‑positive ALL should be prescribed thioguanine in combination with a tyrosine kinase inhibitor per policy

Supporting referenceRequirement clarified and aligned to NCCN; policy revised to require combination with a tyrosine kinase inhibitor rather than naming specific agents

Regimens, Combinations, and Dosing Guidance

Regimen	Indication / Notes
Combination therapy with other AML agents per protocol	Induction and consolidation treatment of acute myeloid leukemia (AML). Physicians should be experienced in the chosen protocol; dosing per package insert.
Single‑agent initial dosing ~2 mg/kg/day, increase cautiously to up to 3 mg/kg/day if no clinical improvement after 4 weeks	Usual initial dosage for pediatric patients and adults approximately 2 mg/kg/day; if no response after 4 weeks and no leukocyte or platelet depression, may increase to 3 mg/kg/day. Total daily dose may be given at one time.

Regimen	Indication / Notes
Thioguanine prescribed in combination with PCV (procarbazine, lomustine, vincristine)	For recurrent or progressive pilocytic astrocytoma (PA) in adults (off‑label). Carmustine may be used in place of lomustine. Regimen should be FDA‑approved or recommended by NCCN; approval duration: 3 months.

Regimen	Indication / Notes
Thioguanine as specified by prescriber with supporting evidence	Used for acute lymphoblastic leukemia (ALL) as an off‑label indication when prescriber submits supporting evidence. Prescribed regimen must be FDA‑approved or recommended by NCCN; dose must be within FDA maximum limit for any FDA‑approved indication or supported by practice guidelines or peer‑reviewed literature.

Regimen	Indication / Notes
Thioguanine plus a tyrosine kinase inhibitor	For ALL, used in combination with a tyrosine kinase inhibitor when applicable for Philadelphia chromosome‑positive disease; policy language replaces prior explicit mention of Sprycel or imatinib with 'tyrosine kinase inhibitor.' Prescriber must document regimen and supporting evidence as required for off‑label use.

OpenPayer

Thioguanine (Tabloid) coverage for AML and select off-label uses